tag:theconversation.com,2011:/africa/topics/antibiotics-843/articlesAntibiotics – The Conversation2024-02-25T14:16:50Ztag:theconversation.com,2011:article/2237162024-02-25T14:16:50Z2024-02-25T14:16:50ZFAQ: Why are syphilis cases on the rise in Canada?<figure><img src="https://images.theconversation.com/files/577183/original/file-20240221-24-guk2fk.jpg?ixlib=rb-1.1.0&rect=39%2C4%2C3253%2C2552&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Syphilis is a sexually transmitted infection (STI) caused by the Treponema pallidum bacterium.</span> <span class="attribution"><span class="source">(NIAID, cropped from original)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Canada has been experiencing an <a href="https://www.canada.ca/en/services/health/campaigns/syphilis.html">increasing number of syphilis diagnoses since 2016</a>. Numerous provinces have declared outbreaks in recent years, with the highest rates observed in the <a href="https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2023-49/issue-10-october-2023/infectious-congenital-syphilis-canada-2022.html">Northwest Territories, Saskatchewan and Manitoba</a>.</p>
<p>During Sexual Health Week this month, the Chief Public Health Officer of Canada, Dr. Theresa Tam, said the country has experienced an <a href="https://globalnews.ca/news/10294073/canada-syphilis-cases-phac/">“alarming increase” in syphilis cases</a>.</p>
<p>As an infectious disease physician, I know how important it is that Canadians have answers to common questions about syphilis, why it’s spreading and what the symptoms are.</p>
<p>Syphilis is an infection caused by the bacterium <em><a href="https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/treponema-pallidum-pathogen-safety-data-sheet.html">Treponema pallidum</a></em>, and is transmitted either through sexual exposure or from an infected pregnant woman into the developing fetus, resulting in congenital syphilis. </p>
<h2>Why is Canada seeing an increase in cases?</h2>
<p>In 2022, <a href="https://www.canada.ca/en/public-health/news/2024/02/statement-from-the-chief-public-health-officer-of-canada-on-syphilis.html">there were 13,953 reported syphilis cases, the highest seen in recent times, with rates increasing by 109 per cent compared to 2018</a>. While historically, gay, bisexual and other men who have sex with men remain at high risk of syphilis infections, recent years saw a surge in infections in heterosexual women, comprising of 35 per cent of all cases in 2022. This has led to a 600 per cent increase in the rates of congenital syphilis compared to previous years. </p>
<p>The reasons for this dramatic increase are not fully known, <a href="https://doi.org/10.14745%2Fccdr.v48i23a01">but may be attributed to several factors</a>: </p>
<ul>
<li><p>health-care disparity and lack of public health investment in surveillance and prevention as well as mistrust of the health-care system among some populations, such as Indigenous people, Black people and those who use substances, </p></li>
<li><p>introduction of highly effective HIV treatment as well as <a href="https://www.catie.ca/pre-exposure-prophylaxis-prep-0">pre-exposure prophylaxis (PrEP)</a> for HIV prevention may result in a decrease in condom use, </p></li>
<li><p>easier access to sex via online dating portals, and </p></li>
<li><p>rising rates of use of drugs while having sex, called party and play (PnP), coincides with increasing rates of syphilis infections.</p></li>
</ul>
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Read more:
<a href="https://theconversation.com/as-an-indigenous-doctor-i-see-the-legacy-of-residential-schools-and-ongoing-racism-in-todays-health-care-162048">As an Indigenous doctor, I see the legacy of residential schools and ongoing racism in today's health care</a>
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<h2>Who is most at risk?</h2>
<p>Since syphilis is typically a <a href="https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/syphilis/risk-factors-clinical-manifestation.html">sexually transmitted infection</a>, certain <a href="https://doi.org/10.14745%2Fccdr.v48i23a01">high-risk practices</a> are associated with high risk of syphilis infection:</p>
<ul>
<li><p>Individuals who have unprotected sexual intercourse with multiple sex partners.</p></li>
<li><p>Commercial sex workers or those who exchange sex for drugs or money.</p></li>
<li><p>People living with HIV. Canadian studies have estimated the reported prevalence of syphilis to range <a href="https://www.canada.ca/en/public-health/services/emergency-preparedness-response/rapid-risk-assessments-public-health-professionals/risk-profile-infectious-syphilis-outbreaks-emergence-congenital-syphilis.html">between eight and 56 per cent</a> in this group.</p></li>
<li><p>Gay, bisexual and other men who have sex with men.</p></li>
<li><p>People who have been incarcerated and those who inject recreational substances.</p></li>
<li><p>Health Canada has also identified certain <a href="https://www.canada.ca/en/services/health/publications/diseases-conditions/syphilis-epidemiological-report.html#4">high-risk populations</a>, such as those experiencing health and social inequities, predominantly due to lack of accessible health care and screening.</p></li>
</ul>
<h2>What are the symptoms?</h2>
<p>The <a href="https://www.canada.ca/en/public-health/services/diseases/syphilis.html">symptoms of syphilis</a> can be divided into different stages, typically defined by when symptoms begin:</p>
<p><strong>1) Early Syphilis</strong> comprises primary and secondary syphilis, which typically occur within weeks to months following the exposure. This also includes early latent syphilis, an asymptomatic stage of the infection.</p>
<ul>
<li><p><strong>A)</strong> <strong>Primary syphilis</strong> is characterized by appearance of a painless sore at the site of infection, typically on the genitals or inside the mouth.</p></li>
<li><p><strong>B)</strong> <strong>Secondary syphilis</strong> is a systemic illness involving different organ systems. It presents with a diffuse body rash, fever, fatigue and sore throat. Wart-like skin lesions known as condyloma lata, alopecia (hair loss) and hepatitis may also occur in this stage.</p></li>
<li><p><strong>C)</strong> <strong>Early latent syphilis</strong> is an asymptomatic stage of the infection within a year of the initial exposure. It is diagnosed with positive blood tests in the absence of any symptoms. </p></li>
</ul>
<p><strong>2) Late Syphilis</strong> occurs in infected patients who do not receive treatment in the earlier stages and usually develops anywhere from one to 30 years after the initial infection. It is categorized into tertiary syphilis and late latent syphilis.</p>
<ul>
<li><p><strong>A)</strong> <strong>Tertiary syphilis</strong> involves chronic inflammation of the body, and may include skin, bones and other internal organs, specifically the cardiovascular system, brain and spinal cord. </p></li>
<li><p><strong>B)</strong> <strong>Late latent syphilis</strong>, much like early latent syphilis, is an asymptomatic stage of the infection, but in this case acquired more than a year previously. It is diagnosed based on positive blood tests. </p></li>
</ul>
<p><strong>3) Neurosyphilis</strong> can occur at any time during the course of infection, and may present in different forms, including meningitis, stroke, or vision or hearing loss. </p>
<h2>How is it transmitted?</h2>
<p>Syphilis is transmitted through direct exposure to an infectious lesion or sore on the skin (also called a chancre) <a href="https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/treponema-pallidum-pathogen-safety-data-sheet.html">during sexual intercourse or activity, including oral sex</a>. Additionally, <a href="http://www.bccdc.ca/health-info/diseases-conditions/syphilis">sharing sex toys</a> can also transmit infection between an infected individual and an uninfected one. </p>
<p>Congenital syphilis is acquired when the bacteria is passed through the placenta to a developing fetus, from an untreated pregnant person.</p>
<p>It should be noted that syphilis does not transmit through sharing utensils, toilet seats, bathtubs, swimming pools or clothes because the bacterium dies quickly outside the body. </p>
<h2>How is syphilis treated?</h2>
<p>Syphilis is an <a href="https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/syphilis.html#a1.4">easily treatable infection and duration of antibiotics is determined by the stage of the disease</a>. Early syphilis is treated with a one-time injection of the penicillin antibiotic into the buttock. Late syphilis is treated with three injections of penicillin, each a week apart, over three weeks. Neurosyphilis and syphilis involving the eyes or ears is typically treated with intravenous antibiotics for two weeks.</p>
<p>Alternative options for people who are either allergic to penicillins or cannot tolerate it include oral antibiotics, such as doxycycline or a once-daily intravenous antibiotic, called ceftriaxone. </p>
<h2>How can it be prevented?</h2>
<figure class="align-center ">
<img alt="Photo of two condoms in red packages" src="https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=432&fit=crop&dpr=1 600w, https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=432&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=432&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=543&fit=crop&dpr=1 754w, https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=543&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/577185/original/file-20240221-20-6rivan.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=543&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Studies suggest that condoms reduce the risk of syphilis by around 90 per cent when used consistently.</span>
<span class="attribution"><span class="source">(Pixabay)</span></span>
</figcaption>
</figure>
<p>Syphilis is a preventable disease. It is important for high-risk and sexually active individuals to access counselling about safe sex practices and the importance of screening for sexually transmitted infections (STI screening). </p>
<p>Studies suggest that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660551/">condoms reduce the risk of syphilis</a> by around 90 per cent when used consistently.</p>
<p>Several <a href="https://www.cdc.gov/std/treatment/doxycycline-as-pep-toe.htm">recently published studies</a> have reported promising outcomes in STI prevention (including gonorrhea, chlamydia and syphilis) with the use of an oral antibiotic — 200 milligrams of doxycycline — taken once within 24 to 72 hours after high-risk or condom-less sexual exposure. This is called post-exposure prophylaxis.</p>
<p>Additionally, easy and early access to health care and STI screening, as well as availability of post-exposure prophylaxis with the oral antibiotics, is important in preventing transmission to others. </p>
<p>With syphilis cases on the rise in Canada, it is important to know that the infection is treatable. Prevention is key not only to individual health but also to slowing its spread.</p><img src="https://counter.theconversation.com/content/223716/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Huma Saeed does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>With the alarming rise in syphilis cases in recent years, it’s important to know what it is, how it’s spread and who is most at risk.Huma Saeed, Assistant Professor of Medicine, Division of Infectious Diseases, Schulich School of Medicine and Dentistry, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2221792024-02-21T13:13:29Z2024-02-21T13:13:29ZAntibiotic use on Kenya’s dairy farms is putting consumers and animals at risk<p>Farmers often use antibiotics to keep their livestock healthy. They’re sometimes used as “quick fixes”, to avoid more costly management measures like regular disinfection, waste management, routine vaccination or provision of clean drinking water. </p>
<p>Animal husbandry now accounts for about <a href="https://doi.org/10.1073/pnas.1503141112">two thirds</a> of the global consumption of antibiotics. As livestock and fish production grows, by 2030 the consumption of antibiotics is <a href="https://doi.org/10.1073/pnas.1503141112">projected to increase</a> by 67%.</p>
<p>Worryingly, this overuse in food animal production can create problems for both animals and people.</p>
<p>It can contribute to the development of antibiotic-resistant bacteria which, through food or environmental exposure such as drinking contaminated water, can be transmitted to people. </p>
<p>This means that some antibiotics may become ineffective in treating human infections. Antibiotic resistant infections are associated with <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">4.95 million deaths</a> globally every year. Sub-Saharan Africa <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">accounts for</a> 22% of these.</p>
<p>Similarly, animals can also become infected with antibiotic-resistant bacteria. This leads to infections that are difficult or impossible to treat.</p>
<p>Our latest <a href="https://www.nature.com/articles/s41598-023-50325-8">study</a>, which focused on the central Kenyan highlands, looked at antibiotic use on smallholder dairy farms as well as antibiotic quality (substandard or counterfeit antibiotics). </p>
<p>Kenya is <a href="https://theconversation.com/kenyas-dairy-sector-is-failing-to-meet-domestic-demand-how-it-can-raise-its-game-176017">one of the largest</a> milk producers in Africa and one of the countries with the largest per capita consumption of milk. About <a href="https://afs.ca.uky.edu/dairy/extension/around-the-world">80%</a> of the milk produced in Kenya comes from smallholder farmers. </p>
<p>We found that smallholder farmers weren’t using antibiotics properly and were buying poor quality products. Also, traces of some antibiotics were found in milk.</p>
<p>This puts the health of both people and animals at risk.</p>
<h2>Antibiotic access and use</h2>
<p>For our study, we collected data from 248 dairy farms and 72 veterinary drug stores between February 2020 and October 2021. This included milk samples and the antibiotics themselves.</p>
<p>Most dairy farms surveyed reported using antibiotics at least once in the past year. This is not unusual – cows get sick. Dairy cows are especially prone to getting udder infections. </p>
<p>Antibiotics were used to treat and to prevent infections. Most were obtained through animal health service providers. A small number (6%) were bought directly from veterinary drug stores or other farmers. </p>
<p>Antibiotics were often sold without a prescription, and based on farmers’ own diagnosis. These are imprudent practices – the wrong antibiotic could be used to treat an infection or antibiotics could be overused. </p>
<p>The improper or excessive use of antibiotics in dairy farming can lead to the development of antibiotic-resistant bacteria. This then leads to economic losses for farmers, because animals will be less productive and the cost of treatment will grow. </p>
<p>It’s estimated that, as a result of antimicrobial resistance, livestock output could <a href="https://documents1.worldbank.org/curated/en/323311493396993758/pdf/final-report.pdf#page=17">fall by 11% by 2050</a>, with the highest decline in low income countries.</p>
<p>There’s also <a href="https://www.liebertpub.com/doi/full/10.1089/fpd.2017.2411">the risk</a> of these antibiotic-resistant bacteria being transmitted to humans, either directly through contact with animals or indirectly through the consumption of milk and dairy products. This can lead to infections that are difficult to treat, posing a public health risk. </p>
<h2>Antibiotics found in milk</h2>
<p>Also worrying, in this study we detected nine antibiotics in milk. Three samples exceeded <a href="https://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCXM%2B2%252FMRL2e.pdf">global standards</a>. Antibiotics can get into milk supplies when withdrawal times are not strictly followed.</p>
<p>The presence of antibiotic residues in milk – even at low levels – can pose health risks to consumers, particularly those who are allergic to specific antibiotics. </p>
<p>Even for those who aren’t allergic, prolonged exposure to low levels of antibiotics <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255607/">may contribute</a> to the development of antibiotic-resistant bacteria.</p>
<h2>Quality of antibiotics</h2>
<p>The study also examined the quality of antibiotics available in veterinary drug stores in central Kenya. </p>
<p>Poor quality, substandard, or counterfeit antibiotics can lead to ineffective treatment and prolonged illness. Low-quality antibiotics are even more likely to contribute to the development of antibiotic-resistant bacteria. This is because they won’t fully eradicate the pathogen (disease-causing bacteria), allowing them to adapt and become resistant. </p>
<p>Almost 44% of the antibiotics we tested were of poor quality. This has considerable implications for the efficacy and safety of these drugs. It can also contribute to antibiotic resistance.</p>
<h2>Implications</h2>
<p>The findings of the study underscore the need for better management practices on Kenya’s dairy farms. This includes:</p>
<ul>
<li><p>stricter regulation of antibiotic sales </p></li>
<li><p>improved veterinary oversight </p></li>
<li><p>education of farmers about the risks of antibiotic misuse. </p></li>
</ul>
<p>For a country like Kenya, where agriculture plays a significant role in the economy, ensuring livestock is healthy and productive is crucial for both farmers and the country. </p>
<p>We recommend a few steps for policymakers to take:</p>
<ul>
<li><p>strengthen regulations around antibiotic use in livestock</p></li>
<li><p>enhance surveillance and monitoring systems for antibiotic residues in milk</p></li>
<li><p>improve the quality control of antibiotics sold in veterinary drug stores</p></li>
<li><p>educate farmers about the responsible use of antibiotics</p></li>
<li><p>promote better animal husbandry practices that reduce the reliance on antibiotics.</p></li>
</ul><img src="https://counter.theconversation.com/content/222179/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dishon Muloi receives funding CGIAR Trust Fund, the Fleming Fund, the German Federal Ministry of Economic Cooperation and Development, and the Danish International Development Agency.</span></em></p><p class="fine-print"><em><span>Arshnee Moodley receives funding from the CGIAR Trust Fund, the Fleming Fund, the German Federal Ministry of Economic Cooperation and Development, Danish International Development Agency, and International Centre for Antimicrobial Resistance Solutions.</span></em></p>Kenya’s smallholder farmers aren’t using antibiotics properly, some are of poor quality and some antibiotics are being found in milk.Dishon Muloi, Research scientist, International Livestock Research Institute Arshnee Moodley, AMR Team Leader, CGIAR System OrganizationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2215112024-01-29T14:53:48Z2024-01-29T14:53:48ZFrom mud and vinegar to 3D printing skin, the way we treat wounds still challenges humanity<p>Whether it’s the sting of a paper cut or the trauma of battle injury, wounds are woven into the tapestry of human experience. And since ancient times, we’ve fought the enemy that lurks within them – infection. </p>
<p>The constant threat of injury on the battlefield led to the search for new ways to combat wound infection. But early surgical procedures lacked the sterile instruments available today, meaning that for many years, surgery came with the added risk of post-operative <a href="https://cha.com/wp-content/uploads/2017/11/AJIC-2012-Infection-Control-Through-the-Ages.pdf">wound infection</a>, resulting in high numbers of deaths. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601883/">Ancient practices</a>, such as using oils, mud, turpentine, or honey to treat wounds, were common around 2000BC. The Greek physician Hippocrates (460-377BC) <a href="https://www.dermatologytimes.com/view/acetic-acid-and-wound-healing">used vinegar</a> to clean wounds, followed by bandaging to keep dirt at bay.</p>
<p>While the first hospitals were <a href="https://scientificsurgery.bjs.co.uk/article/the-surgery-of-theodoric-ca-a-d-1267-translated-from-the-latin-by-eldridge-campbell-m-d-and-james-colton-m-a-volume-i-books-i-and-ii-8-38-x-5-12-in-pp-223-xi-with-coloured-front/">established</a> in Europe in the middle ages, they were dangerous and brutal places. Wound infection rates were high because of unsanitary conditions and the use of cautery, which involved pushing a burning iron into a patient’s wound until it reached the bone.</p>
<figure class="align-center ">
<img alt="A drawing of a pot containing a fire with several medical instruments poking out of it." src="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A receptacle for burning coal to heat cautery instruments.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/gcg933n2/images?id=jghkdnp4">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>By the 1860s, the pioneering surgeon Joseph Lister had revolutionised wound infection treatment by introducing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895849/">carbolic-acid-soaked bandages</a>. And Robert Wood Johnson, who founded Johnson & Johnson, <a href="https://wounds-uk.com/journal-articles/sterilised-gauze-and-baby-powder-robert-wood-johnson-i-and-frederick-barnett-kilmer/">produced</a> the first sterile gauze bandages by 1890. The combination of antiseptic and sterile bandage marked a turning point in the evolution of wound treatment and infection control.</p>
<p>The discovery of penicillin by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">Alexander Fleming</a> in 1928 was also a pivotal moment in the treatment of wound infections. By the 1940s, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369031/">penicillin</a> was being used to treat second world war soldiers who had wound infections that would have been deemed fatal in previous years. For less serious wounds, Lister’s approach of using a dressing and an antiseptic was still used.</p>
<p>Substances like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756674/">silver</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/12914356/">iodine</a> have also been recognised for their antimicrobial properties since the 1800s. Iodine, though effective, caused pain and skin discolouration until safer and less painful formulations were developed in 1949. <a href="https://bnf.nice.org.uk/wound-management/antimicrobial-dressings/">These formulations</a> endure in modern wound dressings.</p>
<p>For everyday cuts and scrapes, a simple cleaning with water and application of antiseptic cream is usually enough. This helps to prevent the inadvertent introduction of bacteria into the wound, minimising the risk of additional pain and swelling. </p>
<p>But while most wounds nowadays heal without issue, some become become infected. Research published in 2021 showed that <a href="https://wounds-uk.com/wp-content/uploads/sites/2/2023/02/68803cd147c4d81a02b9cc56823f19a1.pdf">3.8 million</a> people were having their wounds managed by the NHS between 2017 and 2018, up 71% from between 2012 and 2013. They included surgical wounds, leg ulcers and burns. This shows how hard it can be to care for wounds that are difficult to heal and particularly susceptible to infections.</p>
<h2>Modern-day challenges</h2>
<p>One of the biggest challenges in the modern-day treatment of wound infection is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">antibiotic resistance</a>. This happens when bacteria develop the ability to defeat the drugs designed to kill them. Resistant infections can be difficult, and sometimes impossible, to treat. </p>
<p>Many bacteria have also become resistant to the antimicrobial ingredients used in wound dressings. This is the case for <a href="https://www.sciencedirect.com/science/article/pii/S0195670104005201">silver-based</a> wound dressings, which are often used to treat chronic wound infections. This type of wound characteristically <a href="https://www.nature.com/articles/s41572-022-00377-3">fails to heal</a>, and can remain an open, infected wound for many months – or even years. As well as the devastating effect on people’s quality of life, this also places a huge financial burden on the NHS.</p>
<p>The constant fight against wound infections drives extensive research for new, safe and effective treatments. While progress is being made, a crucial hurdle lies in the <a href="https://academic.oup.com/jacamr/article/3/1/dlab027/6186407">limitations</a> of laboratory testing methods. These tests, while necessary for regulatory approval, often fail to capture the nuanced realities of wounds in the human body. </p>
<p>No two people are the same and no two wounds are the same either. This can lead to situations where treatments shine in the lab but ultimately prove ineffective in real patients.</p>
<h2>Creating wound models</h2>
<p>In response to this, scientists are tackling the limitations of lab tests by creating more realistic synthetic wound models. Some are even <a href="https://pubmed.ncbi.nlm.nih.gov/30172300/">3D printing</a> human skin (using leftovers from surgical procedures), or animal skin, complete with artificial body fluids, such as pus. The aim is to create a model environment that mimics real wounds more accurately. </p>
<p>Recently, my own <a href="https://pubmed.ncbi.nlm.nih.gov/36678466/">research group</a> has made strides in developing lab models that act like real chronic wounds when treated with antimicrobial dressings. While not perfect, our models are a step in the right direction, contributing to the development of formulations with promising potential for treating wound infections in the future.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/we-built-a-human-skin-printer-from-lego-and-we-want-every-lab-to-use-our-blueprint-203170">We built a human-skin printer from Lego and we want every lab to use our blueprint</a>
</strong>
</em>
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<p>As we navigate the complexities of wound care, the quest for new, effective and safe treatments continues, driven by the efforts of scientists worldwide. We are working towards a future where the management of difficult-to-heal wounds and infections improves, enhancing both individual wellbeing and the efficiency of health systems.</p><img src="https://counter.theconversation.com/content/221511/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Maddocks does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Keeping wounds clean and infection free has challenged people for thousands of years.Sarah Maddocks, Lecturer in Microbiology, Cardiff Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2205642024-01-05T14:54:09Z2024-01-05T14:54:09ZNew antibiotic zosurabalpin shows promise against drug-resistant bacteria – an expert explains how it works<figure><img src="https://images.theconversation.com/files/567989/original/file-20240105-24-a6i28q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5120%2C2880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Carbapenem-resistant Acinetobacter baumannii is classified as a priority 1 critical pathogen by the World Health Organization</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-science-laboratory-portrait-beautiful-black-1922200124">Gorodenkoff/Shutterstock</a></span></figcaption></figure><p>Researchers have <a href="https://www.nature.com/articles/s41586-023-06799-7">identified</a> an entirely new class of antibiotic that can kill bacteria that are resistant to most current drugs. </p>
<p>Zosurabalpin is highly effective against the bacterium carbapenem-resistant <em>Acinetobacter baumannii</em> (Crab), which is <a href="https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed">classified</a> as a “priority 1” pathogen by the World Health Organization due to its growing presence in hospitals.</p>
<p>Crab <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137960/">can kill</a> up to 60% of people infected with it. It commonly causes infections of the urinary tract, respiratory tract and blood stream, potentially leading to sepsis. It is responsible for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913636/">around 20%</a> of infections in places like hospitals, care homes or other similar healthcare settings.</p>
<p>Antibiotics commonly work by crossing the cell wall that surrounds infectious bacteria to reach the vital machinery inside. Once inside the cell, antibiotics block that machinery in such a way as to either stop the bacteria from growing or to cause cell death. </p>
<p>Crab is a clinical challenge as it has a double-layered cell wall, a feature that microbiologists describe as “<a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/gram-negative-bacteria">gram negative</a>”. This means that antibiotics need to cross both layers to reach the vital machinery inside the bacteria to kill them and treat the infection. </p>
<p>An exception to this rule is penicillin-based antibiotics, where the target is in the cell wall itself. These antibiotics, known as <a href="https://www.bmj.com/content/344/bmj.e3236">carbapenems</a>, were derived from penicillin some 48 years after it was first discovered and still work in the same way. However, they have undergone clever chemical modification to prevent bacteria successfully evolving to resist them. This makes them a vital part of treating infections like those caused by <em>Acinetobacter baumannii</em>. </p>
<p>But Crab, the superbug version of this infection, has developed the ability to break down carbapenems, giving it an evolutionary upper hand, which has led to its rise to supremacy in hospitals. </p>
<h2>Zosurabalpin</h2>
<p>This new class of antibiotic, zosurabalpin, is shown to be highly effective against Crab both in the laboratory and in infected animals. Researchers tested zosurabalpin against more than 100 Crab samples from patients suffering from the infection. The research team, <a href="https://www.nature.com/articles/s41586-023-06799-7">found</a> that zosurabalpin was able to kill all of these bacterial strains. It could also kill the bacteria in the bloodstream of mice infected with Crab, preventing them from developing sepsis. </p>
<p>Crab has the ability to make a toxin called <a href="https://www.sciencedirect.com/topics/neuroscience/lipopolysaccharide">lipopolysaccharide</a> that it uses as part of its weaponry for infecting people and which it normally embeds into its outer cell wall. </p>
<p>Zosurabalpin works by blocking a molecular machine called <a href="https://www.nature.com/articles/s41586-023-06873-0">LptB2FGC</a> that transports the lipopolysaccharide toxin from the inside barrier to the outside one. This makes the toxin build up inside the bacteria, causing the Crab cells to die. Essentially, the bacteria pull the pin out of their own grenade but zosurabalpin stops them from being able to throw it. </p>
<p>This LptB2FGC mechanism is pretty unique to Crab, which has some advantages and disadvantages. The bad news is that zosurabalpin will only kill Crab infections and not those caused by other types of bacteria. This means doctors would need to accurately diagnose patients with this infection to decide if zosurabalpin would be the right drug. </p>
<p>But a major advantage is that the chance of antibiotic resistance emerging is reduced, as this resistance could only emerge from Crab and not other types of bacteria. Hopefully, this could extend the shelf life of this drug. </p>
<p>The researchers say they have already seen some mutations in the drug target, LptB2FGC. However, these only seem to reduce the effectiveness of zosurabalpin, rather than stopping it working entirely. The great news is that this is the first time an antibiotic has been reported to work in this way. It gives microbiologists a new avenue to explore ways to kill our bacterial enemies before they kill us. </p>
<figure class="align-center ">
<img alt="Close up of microscope with lab glassware." src="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Zosurabalpin is effective against the bacteria, Crab, which can kill up to 60% of people infected with it.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/microscope-lab-glassware-science-laboratory-research-530971462">totojang1977/Shutterstock</a></span>
</figcaption>
</figure>
<p>Zosurabalpin is now in phase 1 clinical trial for use in patients infected with Crab. This early testing in humans will help the company developing the drug, Roche, to work out any side effects of the drugs as well as potential toxicity. Most importantly, they need to check that the drug works just as well in humans as it did in mice, and look to see if any antibiotic resistance emerges in the trial patients. </p>
<p>It’s early days and the failure rate for new antibiotic development is high, but scientists are rising to the challenge. This discovery offers significant opportunities to the scientific field as a whole and a vital lifeline in the fight against antibiotic-resistant infections.</p><img src="https://counter.theconversation.com/content/220564/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Cox receives research funding from UKRI, charities and industry.
He is Co-Director of the Antibiotic Discovery Accelerator (ABX) Network </span></em></p>Zosurabalpin is highly effective against dangerous bacterium Crab, which can kill up to 60% of people infected with it.Jonathan Cox, Senior Lecturer in Microbiology, Aston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2188792023-12-11T22:10:48Z2023-12-11T22:10:48ZAntimicrobial resistance now hits lower-income countries the hardest, but superbugs are a global threat we must all fight<figure><img src="https://images.theconversation.com/files/564957/original/file-20231211-23-x9nrkx.jpg?ixlib=rb-1.1.0&rect=907%2C341%2C5083%2C3646&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While antimicrobial resistance is a threat to all humanity, a tale of two worlds emerges, highlighting the heightened vulnerability of low- and middle-income countries.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/antimicrobial-resistance-now-hits-lower-income-countries-the-hardest-but-superbugs-are-a-global-threat-we-must-all-fight" width="100%" height="400"></iframe>
<p>Antimicrobial resistance (AMR) is one of the World Health Organization’s <a href="https://www.who.int/news-room/photo-story/photo-story-detail/urgent-health-challenges-for-the-next-decade?utm_source=STAT+Newsletters&utm_campaign=1931cb646b-MR_COPY_02&utm_medium=email&utm_term=0_8cab1d7961-1931cb646b-150708293">most urgent health challenges</a> for the next decade. While AMR is a global threat, a tale of two worlds emerges, highlighting the heightened vulnerability of low- and middle-income countries (<a href="https://data.worldbank.org/country/XO">LMICs</a>). </p>
<p>Misuse of antimicrobials worldwide has accelerated the evolution of <a href="https://www.who.int/health-topics/antimicrobial-resistance">antimicrobial resistance</a>. For instance, in many countries, antibiotics are available over the counter, and even when their use is more regulated, the Centers for Disease Control has estimated that in the United States, <a href="https://www.cdc.gov/antibiotic-use/data/outpatient-prescribing/index.html">one in three antibiotic prescriptions</a> were unnecessary. </p>
<p>Likewise, most of the antibiotics are not even given to humans. As much as 80 per cent of the total consumption is <a href="https://doi.org/10.1056/NEJMp1311479">used in livestock</a> to promote growth, and to treat or prevent infections. </p>
<p>This has facilitated bacteria and other microorganisms to become resistant to the drugs that were once effective in treating them — sometimes called <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">superbugs</a>. This problem was associated with <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">4.95 million deaths</a> worldwide in 2019.</p>
<h2>A ‘silent pandemic’</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="clusters of round ivory shapes against a blue background" src="https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=453&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=453&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=453&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=570&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=570&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=570&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Microscopic view of methicillin-resistant Staphylococcus aureus (MRSA) bacteria.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>If we don’t take action, things could get even worse. Reports predict that by 2050, AMR could cause <a href="https://amr-review.org/">10 million deaths</a> each year and cost the world <a href="https://www.who.int/news/item/22-06-2023-who-outlines-40-research-priorities-on-antimicrobial-resistance">US$100 trillion</a>. </p>
<p>Fortunately, many nations are now taking decisive steps toward controlling what the WHO calls a “<a href="https://www.who.int/news-room/articles-detail/global-antimicrobial-resistance-forum-launched-to-help-tackle-common-threat-to-planetary-health">silent pandemic</a>.” Acknowledging the gravity of the situation, high-income countries (<a href="https://data.worldbank.org/income-level/high-income">HICs</a>) such as the U.S. and Canada have <a href="https://doi.org/10.1016/S2214-109X(23)00019-0">implemented robust plans</a> encompassing surveillance, stewardship and policy reforms. </p>
<p>These efforts should undoubtedly be applauded. However, an important principle of the “<a href="https://www.who.int/news-room/questions-and-answers/item/one-health">One Health</a>” approach, which is often neglected, is that this is a global problem, and global collaboration should be prioritized. Low- and middle-income countries bear a <a href="https://doi.org/10.1080/14787210.2021.1951705">disproportionate burden</a> of AMR and require increased resource mobilization, knowledge sharing and international co-operation.</p>
<h2>Contrasting realities</h2>
<p>As a doctoral researcher, I study the evolution of antimicrobial resistance in bacteria, but as an immigrant from Mexico, I am deeply concerned with the disparity observed between high-income and low- and middle-income countries, and their contrasting realities. </p>
<figure class="align-center ">
<img alt="A row of three petri dishes with varying levels of growth" src="https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=240&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=240&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=240&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=302&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=302&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=302&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antimicrobial resistance susceptibility lab tests.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>For instance, there have been great efforts in <a href="https://doi.org/10.1016/S1473-3099(11)70054-8">regulating antibiotic consumption</a> in many HICs, where antibiotic use in livestock has decreased and antibiotics are only accessible under prescription. While there is still room for improvement, there is a less encouraging reality in some LMICs, where antibiotics are usually obtained easily <a href="https://doi.org/10.1016/S1473-3099(11)70054-8">without prescriptions</a> and sometimes used as a way to compensate for the <a href="https://doi.org/10.1080/14787210.2021.1951705">difficulty of accessing health-care professionals</a>. </p>
<p>Likewise, in some LMICs, antibiotic use in animals is predicted to <a href="https://doi.org/10.1073/pnas.1503141112">double by 2030</a> compared to the last decade.</p>
<p>A <a href="https://doi.org/10.1016/j.lana.2023.100594">recent report</a> exploring the burden of AMR in the Americas in 2019 showed the “multiple realities” of the problem. Not surprisingly, by 2019, the four countries with the lowest AMR-linked mortality rates (age-standardized) each had a financed national action plan to combat AMR, while none of the 10 countries with the highest mortality rates did. </p>
<p>Strikingly, <a href="https://www.unicef.org/wash">UNICEF reports</a> that more than half of the world’s population does not have access to safe sanitation and over 2.2 billion people still don’t have access to safe drinking water. This is extremely concerning for a variety of reasons, but good sanitation and hygiene is critical to <a href="https://www.who.int/teams/environment-climate-change-and-health/water-sanitation-and-health/burden-of-disease/wash-and-antimicrobial-resistance#:%7E:text=Improvements%20in%20water%20sanitation%20and,Action%20Plan%20to%20combat%20AMR.">limiting the spread of microbes and reducing the risk of infection</a>.</p>
<p>The current approach taken by most high-income countries is the equivalent of sheltering in the attic, making sure the fire alarm works correctly, while the basement is on fire.</p>
<h2>Worldwide spread</h2>
<figure class="align-right ">
<img alt="Infographic of resistant bacteria spreading around the globe" src="https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Resistant bacteria or resistance genes can spread across countries through travel, immigration, trade and even water and air circulation.</span>
<span class="attribution"><span class="source">(Centers for Disease Control and Prevention)</span></span>
</figcaption>
</figure>
<p>Resistant bacteria can evolve anywhere. Even if some countries manage to control the problem within their borders, the risk remains. Resistant bacteria or genes that allow bacteria to grow in the presence of the antibiotic can spread across countries through various means, including travel, immigration, trade and even natural processes like water and air circulation. </p>
<p>Such is the case of the resistance gene <a href="https://doi.org/10.1128/aac.00774-09">NDM-1</a>, which was first described in 2009. Only five years after the initial report, this resistance gene was present in virtually the <a href="https://doi.org/10.1111/1469-0691.12719">whole world</a>.</p>
<p>We have all observed the phenomenon of worldwide spread firsthand, as the COVID-19 pandemic vividly demonstrates how pathogens can <a href="https://coronavirus.jhu.edu/map.html">rapidly traverse the globe</a>. </p>
<h2>Communication and collaboration</h2>
<p>It is crucial for nations to enhance communication channels and promote education regarding AMR in several sectors, including the general public, health-care providers, farmers and veterinarians. In addition to this, there is a pressing need to establish robust surveillance systems that can promptly detect outbreaks and enable swift action. </p>
<p>Effective cross-border communication could be realized through standardizing surveillance systems. This would enable accurate comparisons of results between countries. Moreover, it facilitates the sharing of valuable resources, equipment, qualified personnel and access to training opportunities. </p>
<p>Both HICs and LMICs should collaborate closely to implement measures aimed at reducing infection rates, such as improved sanitation practices. This collaboration encourages the exchange of knowledge and expertise, enabling the adoption of best practices globally.</p>
<p>The United Kingdom government set a good example in August, when it allocated <a href="https://www.gov.uk/government/news/210-million-to-tackle-deadly-antimicrobial-resistance">£210 million</a> (about C$360 million) to tackle AMR across Asia and Africa over the next three years, understanding that this threat cannot be fought from its own trenches. These resources will increase surveillance in 25 countries where the AMR threat is highest, and will also be used to upgrade laboratories and strengthen the health workforce in those countries. </p>
<p>To effectively combat AMR, global co-operation is not a luxury but a necessity. HICs must recognize their responsibility to support LMICs in addressing this crisis. By sharing resources, knowledge and expertise, we can collectively mitigate the threat of AMR. </p>
<p>By safeguarding the effectiveness of antibiotics, we protect ourselves and future generations from the devastating consequences of antimicrobial resistance. Together, we can make a difference in the global fight against superbugs.</p><img src="https://counter.theconversation.com/content/218879/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Laura Domínguez has received funding from FRQNT, Concordia University and Mitacs. </span></em></p>The contrasting realities of antimicrobial resistance between high-income countries and low- and middle-income countries demands international co-operation to effectively fight superbugs.Laura Domínguez, Doctoral Researcher and Public Scholar, Biochemistry, Concordia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2176932023-11-17T13:21:44Z2023-11-17T13:21:44ZAntimicrobial resistance is a silent killer that leads to 5 million deaths a year. Solutions must include the poor<p>Microbes such as bacteria, viruses, parasites and fungi form part of our everyday lives – they live in us, on us and around us. </p>
<p>We need them for healthy digestion, immune function, and the synthesis of essential nutrients, and we depend on them for farming and industrial processes.</p>
<p>But microbes also cause disease in people, animals and plants. That is why science has developed an arsenal of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995183/">antimicrobials</a> that kill them or slow their spread.</p>
<p>Over time, microbes develop resistance to antimicrobials, and some eventually evolve into so-called “superbugs” that no longer respond to the drugs. So we see more and more <a href="https://pubmed.ncbi.nlm.nih.gov/29773743/">untreatable infections</a> appearing in hospitals and communities.</p>
<p>This phenomenon, known as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768623/">antimicrobial resistance</a> (AMR), means that common illnesses and diseases may become life-threatening again.</p>
<p>Recent figures show that antimicrobial resistance has been linked to <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">close to 5 million deaths annually</a> – more than the total combined death toll of HIV/AIDS and malaria. </p>
<p>It is further estimated that deaths related to drug-resistance <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">could increase to 10 million per year</a> by 2050, overtaking cancer as a leading cause of death worldwide.</p>
<p><a href="https://www.who.int/news-room/events/detail/2023/11/18/default-calendar/world-amr-awareness-week-2023#:%7E:text=WAAW%20is%20celebrated%20from%2018,It%20affects%20us%20all.">World AMR Awareness Week</a> aims to improve awareness and understanding of this silent killer. </p>
<h2>Remembering the poor</h2>
<p>We need urgent global action to counter antimicrobial resistance. However, current efforts that focus on solutions developed in high-income settings may not be suited to the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861125/">societal and economic challenges in low- and middle-income countries</a>.</p>
<p>We are members of a multidisciplinary <a href="https://www.thebritishacademy.ac.uk/projects/just-transitions-to-contain-antibiotic-resistance-while-minimising-potential-burdens-and-harms/">Global Convening Programme</a> set up by <a href="https://www.thebritishacademy.ac.uk/">The British Academy</a> to look into solutions to this problem that are fair and inclusive. Our collective expertise includes science communication, epidemiology, ethics and human rights.</p>
<p>If we want people to become less dependent on antibiotics, we must address <a href="https://www.nature.com/articles/s41586-021-03694-x">the factors that create dependency on antibiotics in the first place</a>.</p>
<p>Antimicrobial resistance is a global issue, but there are some regional differences. </p>
<p><a href="https://doi.org/10.1016/S0140-6736(21)02724-0">Most human deaths from antimicrobial resistance occur in sub-Saharan Africa</a>. Drug resistance is a growing concern in <a href="https://hal.science/hal-02559257/file/1-s2.0-S1473309918300719-main.pdf">malaria</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/30339803/">tuberculosis</a> in these regions.</p>
<p>Low-income environments often go hand in hand with the use of cheap antimicrobials that may be of poor quality or even falsified. These create the <a href="https://www.ncbi.nlm.nih.gov/books/NBK97126/">ideal conditions for resistance to emerge</a>.</p>
<p>Many are sold over the counter for self-diagnosed ailments. </p>
<h2>Antibiotics, animals and pandemic risk</h2>
<p>Antibiotics are among the most widely used antimicrobials. Between 2000 and 2015 the use of antibiotics increased by <a href="https://www.pnas.org/doi/abs/10.1073/pnas.1717295115?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">65%</a> worldwide. </p>
<p>Globally, however, more antibiotics are used in <a href="https://www.science.org/doi/10.1126/science.aao1495">animals</a> and agriculture than for human health. Of all antimicrobials, <a href="https://doi.org/10.1371/journal.pgph.0001305">73%</a> are used in animals raised for food. </p>
<p>In September 2016, the United Nations adopted a unanimous <a href="https://digitallibrary.un.org/record/845917">resolution</a> recognising the inappropriate use of <a href="https://www.science.org/doi/10.1126/science.aao1495">antimicrobials in animals</a> as a leading cause of rising antimicrobial resistance. </p>
<p>Farmers rely on antibiotics to prevent disease outbreaks and <a href="https://www.nature.com/articles/s41599-018-0152-2">boost</a> production, especially where animals are kept in unhygienic and overcrowded conditions, and where farmers don’t have access to veterinary care. There antibiotics serve as “<a href="https://gh.bmj.com/content/4/4/e001590">quick fixes</a>”.</p>
<p>In one study in rural Uganda a woman told researchers she was using left-over antibiotics to treat family members and her chickens. This repurposing of antibiotics is seen as a way to <a href="https://www.tandfonline.com/doi/full/10.1080/01459740.2022.2047676">survive and make a living</a>.</p>
<p>Experts warn that antimicrobial resistance in <a href="https://www.science.org/doi/10.1126/science.aaw1944">farm animals</a>, if unchecked, could lead to the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200017/pdf/JNMA-60-246-225.pdf">next pandemic</a>.</p>
<h2>Everybody is exposed, everywhere</h2>
<p>Environmental pollution in the form of <a href="https://wellcome.org/sites/default/files/antimicrobial-resistance-environment-report.pdf">antimicrobial residues spreads</a> to soils, rivers, streams and oceans, as well as food and drinking water, and contributes to resistance. Everyone is exposed to antimicrobials, especially antibiotics, even if they don’t take these medicines themselves. </p>
<p>This kind of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995183/">pollution</a> is aggravated when antimicrobials are used and disposed of negligently. </p>
<h2>The global response needs to be fair to all</h2>
<p>We are calling for a new approach to antimicrobial resistance that prioritises <a href="https://doi.org/10.1016/S0140-6736(23)01687-2">equity and sustainability</a>. </p>
<p>Policy options must be carefully considered with all those involved and by <a href="https://www.medrxiv.org/content/10.1101/2023.10.06.23296658v1">embedding public and community voices</a> without having pre-determined solutions in mind. </p>
<p>“Simple” solutions may disadvantage communities that shoulder the heaviest burden of infections and poor healthcare. For example, banning the over-the-counter sale of antibiotics may help to curb excessive use, but it could also deny life-saving treatment for people who have no other options. Similarly, without antibiotics, small-scale pig and poultry farmers may <a href="https://pubmed.ncbi.nlm.nih.gov/36762463/">no longer be able to make a living</a>. </p>
<p>The solution we are working towards is fair and inclusive. It respects people and their traditions while also benefiting human health, animal welfare and the natural environment.</p><img src="https://counter.theconversation.com/content/217693/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marina Joubert receives funding from The British Academy. </span></em></p><p class="fine-print"><em><span>Sonia Lewycka receives funding from The British Academy and Wellcome. </span></em></p><p class="fine-print"><em><span>Phaik Yeong Cheah does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Antimicrobial resistance is an epidemic that kills close to 5 million people annually. The solutions are complex and must take into account the needs of the poor.Marina Joubert, Science Communication Researcher, Stellenbosch UniversityPhaik Yeong Cheah, Professor of Global Health, University of OxfordSonia Lewycka, Epidemiologist, Oxford University Clinical Research Unit (OUCRU)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2176152023-11-16T11:46:35Z2023-11-16T11:46:35ZAntibiotic resistance: microbiologists turn to new technologies in the hunt for solutions – podcast<figure><img src="https://images.theconversation.com/files/559597/original/file-20231115-23-wi1i4s.jpg?ixlib=rb-1.1.0&rect=6%2C78%2C4001%2C2506&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Testing for antimicrobial resistance in the lab.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-media-plate-on-hand-medical-507859600">AnaLysiSStudiO via Shutterstock</a></span></figcaption></figure><p>The rise of drug-resistant infections is one of the <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">biggest global threats</a> to health, food security and development. Antibiotic-resistant superbugs were estimated to kill <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">1.27 million people</a> in 2019, and the UN projects that drug-resistant diseases could <a href="https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis">cause 10 million deaths a year by 2050</a>. </p>
<p>In this episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> podcast, we hear from a microbiologist at a hospital in Nigeria working on the frontlines against antibiotic resistance, and find out about the new scientific techniques, including artificial intelligence (AI), being deployed to find new potential antibiotics.</p>
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<p>Nubwa Medugu began her medical career in 2008 working in a paediatric unit in Kano, northern Nigeria. A lot of the children had typhoid and had taken antibiotics for it, but had come to hospital because the drugs weren’t working. “The fact that a lot of patients have infections that are very difficult to treat, I didn’t know it was just the tip of the iceberg then,” she says. </p>
<p>Today, Medugu is a clinical microbiologist at the National Hospital Abuja in Nigeria’s capital, and also teaches microbiology at Nile University of Nigeria. Her work involves analysing the hospital’s lab results for drug-resistant infections, and “the problem seems to have gotten worse”. She says it’s now “almost impossible” to find infections that are not resistant to at least one antibiotic. </p>
<p>Medugu recently <a href="https://www.nature.com/articles/s41598-023-37621-z">published research</a> analysing the level of antibiotic resistance in hospitals in Nigeria, and the types of antibiotics that are proving least effective. What’s most worrying is the number of infections that are resistant even to antibiotics of last resort – those drugs used to treat cases where other antibiotics have failed. “If nothing works, carbapenems usually work, but in this research, resistance to the carbapenems was pretty high … over 60% resistant.”</p>
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Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
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<h2>The hunt for new antibiotics</h2>
<p>Inequality and poverty are a big part of the problem. If people aren’t able to access vaccinations, diagnostic testing, medical advice and the right drugs if they’re infected, this can exacerbate antibiotic resistance. But even in a world where everybody had access to the healthcare they needed, bacteria would still develop resistance to antibiotics. </p>
<p>And so, as the problem deepens, the hunt continues on for new antibiotics. One of the scientists doing that searching is André Hudson, a professor of biochemistry at Rochester Institute of Technology in New York. He uses traditional bio-prospecting techniques to culture potential antibiotics from natural samples such as soil. But Hudson explains that others are now using new techniques to find potential antibiotic compounds. </p>
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<p>With AI, it allows it to go faster. It provides us with things that we cannot even think about, or we don’t even know how to do yet in the lab.</p>
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<p>Another approach is called <a href="https://www.nature.com/articles/455481a">metagenomics</a>, which involves sequencing an entire community of bacteria found in an environmental sample, such as soil or even the <a href="https://theconversation.com/we-found-more-than-54-000-viruses-in-peoples-poo-and-92-were-previously-unknown-to-science-163258">human gut</a>. “Rather than cherry-picking a particular bacteria, I extract all DNA that is present in the soil and sequence the entire community,” explains Hudson. </p>
<p>In September, a group of scientists in Germany, the Netherlands and the US published a paper announcing they’d discovered a potential antibiotic using this method called <a href="https://theconversation.com/could-new-antibiotic-clovibactin-beat-superbugs-or-will-it-join-the-long-list-of-failed-drugs-212774">clovibactin, isolated from uncultured soil bacteria</a>. </p>
<p>Find out more about the fight against antibiotic resistance, and the solutions on the cards, by listening to the full episode of <a href="https://podfollow.com/the-conversation-weekly/view">The Conversation Weekly</a>. A transcript is <a href="https://cdn.theconversation.com/static_files/files/2972/Antibiotic_Resistance_Transcript.docx.pdf?1701940198">now available</a>. </p>
<p>And read more about this topic in a special series, <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">The dangers of antibiotic resistance</a>, in which experts explore how we got here and the potential solutions.</p>
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<p><em>This episode was written and produced by Mend Mariwany and Gemma Ware with assistance from Katie Flood. Eloise Stevens does our sound design, and our theme music is by Neeta Sarl. Gemma Ware is the executive producer of the show.</em></p>
<p><em>You can find us on X, formerly known as Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/">theconversationdotcom</a> or <a href="mailto:podcast@theconversation.com">via email</a>. You can also subscribe to The Conversation’s <a href="https://theconversation.com/newsletter">free daily email here</a>.</em></p>
<p><em>Listen to <em>The Conversation Weekly</em> via any of the apps listed above, download it directly via our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a> or find out <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">how else to listen here</a>.</em></p><img src="https://counter.theconversation.com/content/217615/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>André O. Hudson receives funding from the National Institutes of Health. Nubwa Medugu does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>From the frontline battle against antibiotic resistance in Nigeria, to the techniques being used to find new antibiotics. Listen to The Conversation Weekly podcast.Gemma Ware, Editor and Co-Host, The Conversation Weekly Podcast, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2070252023-11-15T19:04:23Z2023-11-15T19:04:23Z‘Phage therapy’ could treat some drug-resistant superbug infections, but comes with unique challenges<figure><img src="https://images.theconversation.com/files/557066/original/file-20231101-25-9niwf.jpg?ixlib=rb-1.1.0&rect=136%2C528%2C5208%2C3029&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmacist-nurse-stethoscope-analyzing-healthcare-treatment-2052272615">Shutterstock</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
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<p>As bacteria become resistant to antibiotics, more people will become infected and die of untreatable bacterial infections. By 2050, drug-resistant infections are predicted to kill <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">ten million people a year</a>.</p>
<p>So researchers are desperately seeking viable alternatives. One promising therapy uses specialised viruses called bacteriophages to invade and kill bacteria. They’re called “phages” for short.</p>
<p>This “phage therapy” has been <a href="https://www.bbc.com/news/health-48199915">used</a> to <a href="https://www.bbc.com/news/stories-50221375">treat</a> antibiotic-resistant <a href="https://www.abc.net.au/news/2021-01-15/antibiotic-resistant-superbug-bacteriophage-therapy/12213010">infections</a> in small numbers of people who would have died without another way to kill the bacteria causing their infections.</p>
<p>But phage therapy is complicated, more complicated than prescribing antibiotics and picking up a script from the pharmacy. </p>
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Read more:
<a href="https://theconversation.com/the-rise-and-fall-of-antibiotics-what-would-a-post-antibiotic-world-look-like-213450">The rise and fall of antibiotics. What would a post-antibiotic world look like?</a>
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<h2>What is phage therapy?</h2>
<p>In the wake of COVID, we’re all familiar with viruses that infect human cells. There are also viruses that infect bacteria, known as phages. </p>
<p>Just as viruses that infect humans only affect certain types of human cells, phages prefer to infect certain types of bacteria. MS2 phage, for example, can infect <em>Escherichia coli</em> (<em>E. coli</em>) and some related bacteria – but not all of them. </p>
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<img alt="" src="https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/557068/original/file-20231101-23-aqs9xd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Phages (shown in red) are viruses that attack and infect bacteria (shown in green).</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/bacteriophages-viruses-that-attack-infect-bacteria-1391256956">Shutterstock</a></span>
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<p>Often, phages infect bacteria and just remain there, existing within the bacterium. </p>
<p>Sometimes, phages infect bacteria with lethal consequences for the infected bacterium. This is what can be harnessed and turned into phage therapy.</p>
<p>If the right phage can be found, it can be delivered to the infection site (either intravenously, topically to the skin or by aerosol inhalation), where it will find, infect and kill the bacteria causing the patient’s infection. </p>
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Read more:
<a href="https://theconversation.com/viruses-are-both-the-villains-and-heroes-of-life-as-we-know-it-169131">Viruses are both the villains and heroes of life as we know it</a>
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<p>Since phages don’t infect and cause disease in humans, phage therapy selectively targets and kills the bacteria in the patient, and not the patient. An added bonus is phages leave other beneficial bacteria unaffected, unlike antibiotics.</p>
<h2>So how is phage therapy prepared?</h2>
<p>Before use, the right phage – capable of infecting the bacteria causing the infection – must be matched to target the infecting bacteria. This involves developing comprehensive <a href="https://pubmed.ncbi.nlm.nih.gov/33581425/">phage libraries</a> by isolating and selecting phages with the <a href="https://www.mdpi.com/2079-6382/8/3/126">desired</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323186/">properties</a>. </p>
<p>Fortunately, phages are everywhere – in soil, water, plants, animals and us. Finding and characterising them is straightforward, but takes time.</p>
<p>Successfully matching phage to the specific bacteria causing the patient’s infection requires lab technicians to isolate the bacteria first. This takes one to three days. </p>
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<img alt="Scientist looks through microscope" src="https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/557069/original/file-20231101-25-fwb4ej.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">First, lab technicians must isolate the bacteria causing the patient’s infection.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/health-care-researchers-working-life-science-2340899525">Shutterstock</a></span>
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<p>Then, the isolated bacterium is tested against hundreds of phages from the phage library to find one that can infect and kill that bacterium. The methods are slow, labour-intensive and take another few days. </p>
<p>Finally, when a phage that can kill the bacterium is identified, that specific phage, or a cocktail of multiple lethal phages, must be manufactured and administered to the patient. </p>
<p>Ironically, the unique advantages that make phage therapy a viable treatment for antibiotic-resistant infections bring challenges for treating lots of patients. </p>
<h2>Testing for clinical efficacy is still under way</h2>
<p>Before phage therapy can be approved for widespread use, it must meet the stringent safety and efficacy <a href="https://www.frontiersin.org/articles/10.3389/fcimb.2018.00376/full">requirements</a>. Efforts to achieve this for specific infections are currently underway in academic and commercial research settings.</p>
<p>In the meantime, phage therapy is available in the <a href="https://www.fda.gov/drugs/investigational-new-drug-ind-application/physicians-how-request-single-patient-expanded-access-compassionate-use">United States</a> on an <a href="https://link.springer.com/content/pdf/10.1007/978-3-319-41986-2_52.pdf">ad hoc basis</a> for “compassionate use”. In Australia, a “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9743374/">special access scheme</a>” provides limited access, with efforts to <a href="https://www.phageaustralia.org/">expand access underway</a>.</p>
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Read more:
<a href="https://theconversation.com/do-you-think-you-have-a-penicillin-allergy-you-might-be-wrong-212874">Do you think you have a penicillin allergy? You might be wrong</a>
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<p>Individual instances of phage therapy have <a href="https://www.contagionlive.com/view/from-a-harrowing-experience-comes-a-professional-calling">saved the lives</a> of those who would otherwise have died. But while there is a growing body of research supporting the efficacy of phage therapy, <a href="https://www.frontiersin.org/articles/10.3389/fcimb.2018.00376/full">well-designed clinical trials</a> are needed to establish its effectiveness.</p>
<h2>Manufacturing presents a number of challenges</h2>
<p>Phages are biological products that require careful production and quality-control processes. Propagating phages in the lab is one thing, but preparing them to a standard that can be applied, ingested, instilled or even injected into patients is another. </p>
<p>Developing scalable and standardised methods for phage production, purification and formulation is essential to meet the demand for widespread use. </p>
<p>Phages are made up of DNA or RNA, protein, and sometimes fats (known as lipids), all of which can be compromised if exposed to unfavourable conditions. </p>
<p>Pharmaceutical preparations of phage need to be transported, stored and dispensed in ways that preserve their biological activity, which can vary tremendously.</p>
<figure class="align-center ">
<img alt="petri dish with bacterial culture with phage" src="https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/557071/original/file-20231101-29-bn23t6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Phages can infect the bacteria that cause drug-resistant infections.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/petri-dish-bacterial-culture-phace-activity-1658404837">Shutterstock</a></span>
</figcaption>
</figure>
<h2>Bacteria can become phage-resistant</h2>
<p>Similar to antibiotics, bacteria can develop resistance to phages over time. This can occur through various mechanisms, such as the modification of bacterial surface receptors targeted by phages to gain entry to the bacteria. </p>
<p>Ways to <a href="https://doi.org/10.1146/annurev-virology-012423-110530">minimise or overcome the development of resistance</a> need to be explored to ensure long-term effectiveness. This includes using phage cocktails, staggered administration of single phages or combining phage therapy with other treatments.</p>
<h2>Commercial viability</h2>
<p>Antibiotics aren’t “one size fits all” for bacterial infections, but one antibiotic covers many infections and many different bacteria. Prescribing antibiotics takes moments, treatment can start right away, and they have a large and established industrial, commercial and regulatory framework surrounding them.</p>
<p>In contrast, the customisation involved in delivering phage therapy takes a lot of time, labour and resources. This could make phage therapy relatively expensive.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/could-new-antibiotic-clovibactin-beat-superbugs-or-will-it-join-the-long-list-of-failed-drugs-212774">Could new antibiotic clovibactin beat superbugs? Or will it join the long list of failed drugs?</a>
</strong>
</em>
</p>
<hr>
<p>To prepare bespoke phage preparations on demand, there must be a commercially viable and sustainable pathway to set up and maintain the infrastructure needed.</p>
<p>Much of the technology already exists to modernise, standardise and massively scale the phage therapy pipeline. With continued dedication, collaboration and investment, we have the potential to harness phage therapy as a tool in the fight against drug-resistant infections.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/207025/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christine Carson receives funding from the WA Future Health Research and Innovation Fund, and the CUREator program, a national biotechnology incubator delivered by Brandon BioCatalyst. She has a commercial interest in companies developing diagnostic tests, and preventing viral infections.</span></em></p><p class="fine-print"><em><span>Lucy Furfaro receives funding from the National Health and Medical Research Council (NHMRC) and is associated with Phage Australia.</span></em></p>Researchers are desperately seeking viable alternatives to antibiotics. So what is phage therapy? And how could it help?Christine Carson, Senior Research Fellow, School of Medicine, The University of Western AustraliaLucy Furfaro, NHMRC Emerging Leadership Fellow, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2127742023-11-13T19:46:25Z2023-11-13T19:46:25ZCould new antibiotic clovibactin beat superbugs? Or will it join the long list of failed drugs?<figure><img src="https://images.theconversation.com/files/556012/original/file-20231026-27-9p25k9.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5000%2C3315&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/injured-hand-arm-girl-tied-by-1614690262">Shutterstock</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>Imagine a world where simple infections could become life-threatening, where a small cut could spell disaster, and where doctors couldn’t treat diseases effectively anymore. This isn’t the plot of a science fiction movie – it’s a real concern. </p>
<p>For decades, antibiotics have been used successfully to fight a wide range of bacterial infections. However, overuse of these medicines has led to the development of antibiotic-resistant bacteria, known as “superbugs”. </p>
<p>Scientists are now in a race against time to discover new antibiotics that can defeat these bacteria. While this has been a difficult task, the recently discovered antibiotic <a href="https://www.cell.com/cell/fulltext/S0092-8674(23)00853-X">clovibactin</a> has renewed hope that we can fight our way out of this antibiotic resistance crisis. </p>
<p>So is clovibactin the saviour we’ve been hoping for? Or is it another in a long list of antibiotics that will remain only useful for research? The results so far are mixed.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-rise-and-fall-of-antibiotics-what-would-a-post-antibiotic-world-look-like-213450">The rise and fall of antibiotics. What would a post-antibiotic world look like?</a>
</strong>
</em>
</p>
<hr>
<h2>Remind me, how do antibiotics work?</h2>
<p>Antibiotics work by either directly killing bacteria or preventing them from growing and dividing. They do this by targeting parts of the bacterial cell that are not present in human cells. </p>
<p>Bacteria are surrounded by a cell wall. It might be helpful to imagine the cell walls around bacteria as the walls of a fortress, which helps them survive in the environment. </p>
<p>Antibiotics are like a group of knights trying to breach the walls and take down the enemy inside. Traditional antibiotics, like penicillin, act to weaken these walls. They kill the bacteria and make it easier for our immune system to finish the job. </p>
<p>However, bacteria have evolved to resist these attacks, meaning that antibiotics in some cases no longer have any effect. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
</strong>
</em>
</p>
<hr>
<h2>What about clovibactin?</h2>
<p>Clovibactin works differently. It targets bacteria from the inside out, taking away the bricks that are used to build the wall in the first place. </p>
<p>Bacteria have very limited options when choosing bricks to build their walls, so this approach means that resistance is much less likely to develop. </p>
<p>This mechanism of action is unique and offers hope that we can use clovibactin as a model to develop other antibiotics that act in a similar way. </p>
<p>But significant challenges still lie ahead. </p>
<h2>Why do most antibiotics fail?</h2>
<p>The field of antibiotic discovery is littered with drugs that have failed to progress beyond the early stages of research. </p>
<p>Antibiotic testing usually progresses from the laboratory bench to animal trials and, eventually, to human trials. While some antibiotics are very effective at killing bacteria in the lab, they are not always used to treat patients. </p>
<figure class="align-center ">
<img alt="Female scientist looks in microscope" src="https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/556747/original/file-20231030-27-7gs26l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Some antibiotics are effective in the lab but this doesn’t always translate to humans in the real world.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/female-scientist-in-white-lab-coat-using-a-microscope-4032060/">Edward Jenner/Pexels</a></span>
</figcaption>
</figure>
<p>There are many reasons why this happens that cannot be predicted when an antibiotic is first discovered. An unfortunate, yet common, example is that antibiotics that appear safe in animals may turn out to be toxic at the higher doses required to treat humans. </p>
<p>Such unforeseen complications during the development phase are one part of the reason why <a href="https://wellcome.org/news/its-time-fix-antibiotic-market">more than 98.5%</a> of newly discovered antibiotics never make it out of the lab. </p>
<p>Even for those with a perfect development pathway, the average time to market is nine years at a <a href="https://wellcome.org/news/its-time-fix-antibiotic-market">cost</a> of greater than US$1 billion. </p>
<p>For clovibactin, the early signs look promising. No toxicity in human cells was detected and it successfully <a href="https://www.cell.com/cell/fulltext/S0092-8674(23)00853-X">cured mice infected with golden staph</a>. </p>
<p>However, there are still risks and market forces that may also be against clovibactin. </p>
<h2>Pharmaceutical companies want a return on their investment</h2>
<p>Antibiotics are not particularly profitable drugs and for a drug company to recoup their investment, an antibiotic must kill as many different bacteria as possible. </p>
<p>Health bodies such as the <a href="https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed">World Health Organization</a> and the United States <a href="https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf">Centers for Disease Control</a> have compiled lists of bacteria that pose the greatest threat to humans and for which we have limited treatments. Although clovibactin can kill <em>some</em> of the drug-resistant bacteria on these lists, it is not effective against the most troublesome and damaging bacteria. </p>
<p>Even for those it can kill, it does not appear to be superior to already available drugs, such as vancomycin. </p>
<p>Such shortcomings may prevent clovibactin from gaining future United States Food and Drug Administration (FDA) approval.</p>
<p>Although, scientists may be able to overcome these issues by chemically “tweaking” clovibactin to give it the desired traits. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>Even if it works, we’ll still need other antibiotics</h2>
<p>Although clovibactin offers hope, one new compound alone cannot solve our current antibiotic resistance crisis. In fact, even the <a href="https://www.bio.org/sites/default/files/2022-02/The-State-of-Innovation-in-Antibacterial-Therapeutics.pdf">64 antibiotics</a> currently in clinical trials will be insufficient, particularly as 80% of these will likely hit <a href="https://wellcome.org/news/its-time-fix-antibiotic-market">development hurdles</a>. </p>
<figure class="align-center ">
<img alt="Man looks at medicine bottle in front of cabinet" src="https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/556752/original/file-20231031-25-fcceqd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibiotics need to be effective, safe and ideally, deliver a return on pharma company investment.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/man-hold-medication-bottle-reading-instruction-2262340167">Shutterstock</a></span>
</figcaption>
</figure>
<p>The good news is that more than one-third of these 64 antibiotics <a href="https://www.bio.org/sites/default/files/2022-02/The-State-of-Innovation-in-Antibacterial-Therapeutics.pdf">target</a> infections for which we desperately need new treatments, including tuberculosis and gut infections caused by <em>Clostridium difficile</em>.</p>
<p>As we eagerly await the day new antibiotics become part of our standard medical treatments, it’s crucial for all of us as individuals to continue practising good hygiene and following prescribed antibiotic regimens. </p>
<p>Continuing support for research to combat antibiotic resistance is also needed, not just from governments and non-profits, but also through policies that incentivise private sector investment. </p>
<p>In doing so, we can maintain these effective weapons in the fight against bacterial infections for as long as possible.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/212774/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sacha Pidot receives funding from the National Health and Medical Research Council and the Australian Research Council for research on antibiotics.</span></em></p>Scientists are racing to discover new antibiotics that can defeat these drug-resistant superbugs. So how is the newly developed antibiotic clovibactin different?Sacha Pidot, Molecular microbiologist; laboratory head, The Peter Doherty Institute for Infection and ImmunityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2128742023-11-08T19:10:33Z2023-11-08T19:10:33ZDo you think you have a penicillin allergy? You might be wrong<figure><img src="https://images.theconversation.com/files/555945/original/file-20231025-19-tbp1oy.jpg?ixlib=rb-1.1.0&rect=98%2C160%2C8144%2C5326&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/these-all-possible-causes-shot-young-2148946861">Shutterstock</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">experts explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>Penicillins are the most prescribed class of antibiotics in Australia. Originally derived from a fungus, penicillin antibiotics such as amoxicillin are used to treat common infections, including chest, sinus, ear, urinary tract and skin infections. </p>
<p>Penicillins are effective against a wide range of bacteria that cause common infections. But their activity is not so broad as to impact on good bacteria in our gut like other antibiotic classes do. They’re also cheap and readily accessible.</p>
<p>Up to <a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376#bib1">20%</a> of Australians admitted in hospital say they have a penicillin allergy.</p>
<p>But not everyone who thinks they’re allergic to penicillin actually is. Research from <a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376?via%3Dihub">our team</a> and others suggests that if we assess all these patients, up to 90% are not allergic to it.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-penicillin-the-mould-that-saves-millions-of-lives-63770">Weekly Dose: penicillin, the mould that saves millions of lives</a>
</strong>
</em>
</p>
<hr>
<h2>Why does it matter?</h2>
<p>People who mistakenly think they’re allergic to penicillin may not get the most effective or safest antibiotics to treat their infection. </p>
<p>They are also at greater risk of developing <a href="https://www.sciencedirect.com/science/article/abs/pii/S009167491301467X">multidrug-resistant infections</a> or “superbugs”. This is because the antibiotic will kill off the bacteria that are susceptible to it, but the resistant bacteria are left behind to proliferate and cause further infection.</p>
<p>People who receive second-line antibiotics are more likely to have complications, such as <a href="https://www.sciencedirect.com/science/article/abs/pii/S009167491301467X">antibiotic-induced gut infections</a>. Second-line antibiotics tend to have a wider range of activity, killing both the bacteria causing infection, and the good bacteria required to keep our gut in balance. This allows bugs like <em>Clostridium difficile</em>, which normally lives in our gut but is controlled by other bacteria, to overgrow and cause inflammation. </p>
<p>For the health system, using second-line antibiotics means longer, more complicated hospital stays. Hospital stays for patients with penicillin allergies cost up to <a href="https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2222.2003.01638.x">63% more</a> more than those without. It also results in greater costs for medications and greater resources required to treat the patient. </p>
<h2>Why do people think they’re allergic?</h2>
<p>People incorrectly believe they are allergic to penicillin for a number of reasons. </p>
<p>They may have experienced side effects from penicillin, such as nausea or diarrhoea. But though unpleasant, this doesn’t mean an allergy.</p>
<p>Others had a rash as a child, but this could have been due to the illness itself or an interaction between the virus and the antibiotic. An Epstein-Barr viral infection treated with amoxicillin, for example, <a href="https://pubmed.ncbi.nlm.nih.gov/23589810/">causes</a> a fine, red rash. </p>
<figure class="align-center ">
<img alt="Woman sits it wheelchair in hospital" src="https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It’s important to know your true allergy status when you go to hospital.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/rear-view-senior-asian-woman-sitting-1605865573">Shutterstock</a></span>
</figcaption>
</figure>
<p>Some believe a family history of reactions to penicillin means they cannot take them. But there is no evidence penicillin allergy is inherited. </p>
<p>If some time has passed between exposure, people can lose the allergic response. This is typically seen in adults who had a mild allergy as a child, but lose the response with time, so are said to have “grown out” of their allergy.</p>
<p>Then there are people who have had a genuine and serious reaction to penicillin. This includes anaphylaxis, with profound swelling, breathing difficulties and low blood pressure, and severe life-threatening reactions such as <a href="https://www.ncbi.nlm.nih.gov/books/NBK459323/#:%7E:text=Stevens%2DJohnson%20syndrome%2Ftoxic%20epidermal,in%20over%2080%25%20of%20cases.">Steven-Johnson’s syndrome</a>, which causes widespread blisters and wounds that resemble burns.</p>
<h2>Testing for penicillin</h2>
<p>When someone says they have a penicillin allergy, we first get them to explain what happened with the reaction, including to what antibiotic, in what context and how severe it was. </p>
<p>Then we perform skin tests to further assess the person’s risk of reaction. If skin tests are negative, we can then give the patient the penicillin in question under supervision (a “challenge”) to see if they react. </p>
<figure class="align-center ">
<img alt="Allergist performs skin test on patient's arm" src="https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Skin tests assess a patient’s reaction to the allergen.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/allergy-skin-prick-tests-184605983">Shutterstock</a></span>
</figcaption>
</figure>
<p>Some people can skip the skin tests altogether and go straight to the challenge if the history tells us they are at low risk of reacting.</p>
<p><a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376?via%3Dihub">Our study</a> followed 195 patients who reported a penicillin allergy across six Sydney hospitals. In the first phase, we assessed 85 people and found 82% weren’t allergic to penicillin. </p>
<p>In the second phase, we assessed 110 people, of whom 69% weren’t allergic.
This is slightly lower than research on the population as a whole, because we only looked at people who were referred for an allergy assessment. Many more patients carry an allergy label than those referred for testing.</p>
<p>In our study, eight weeks after their test, just 54% of participants in phase one correctly knew their penicillin allergy status. Some allergic people believed they were not allergic, and many non-allergic people believed they were allergic.</p>
<p>For phase two, we ensured people received a standardised letter outlining their results in addition to having a doctor or nurse explain them. This time, 92% were correct in their understanding when contacted eight weeks later. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>Reducing long waits for allergy tests</h2>
<p>Ruling out allergies among people who think they can’t have penicillin is time- and labour-intensive. The wait time from someone first being referred to an allergy clinic to having testing can be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026071/">up to two years</a>. And it’s usually not available outside major metropolitan hospitals. </p>
<p>We need to improve access to testing and also look at <em>when</em> people can access allergy services. When a person is sick in hospital with a serious infection, it’s not the right time for testing.</p>
<p>We also need to ensure the results of allergy tests translate to the real world so people know their true allergy status. The fragmentation of our medical records are a barrier to clear and effective communication of a patient’s true allergy status, and urgently need to be improved.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/212874/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Winnie Tong has received funding from Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research and Enterprise (SPHERE), Triple I Clinical Academic Group seed grant 2017, and the Balnaves Foundation. The authors would like to acknowledge Professor Andrew Carr, their collaborators and participants on this project. </span></em></p><p class="fine-print"><em><span>Jacqueline Loprete does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Up to 20% of Australians admitted in hospital say they have a penicillin allergy. But not everyone who thinks they’re allergic to penicillin actually is.Winnie Tong, Clinical Immunologist & Allergist, Immunopathologist and Senior Lecturer, UNSW SydneyJacqueline Loprete, Postdoctoral fellow, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134502023-11-07T19:35:17Z2023-11-07T19:35:17ZThe rise and fall of antibiotics. What would a post-antibiotic world look like?<figure><img src="https://images.theconversation.com/files/554665/original/file-20231019-25-r60wx5.jpg?ixlib=rb-1.1.0&rect=11%2C449%2C3982%2C2461&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-blue-and-white-polo-shirt-standing-on-yellow-flower-field-during-daytime-CEFYNiM9xLk">Luke Jones/Unsplash</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>These days, we don’t think much about being able to access a course of antibiotics to head off an infection. But that wasn’t always the case – antibiotics have been available for less than a century. </p>
<p>Before that, patients would die of relatively trivial infections that became more serious. Some serious infections, such as those involving the heart valves, were <a href="https://pubmed.ncbi.nlm.nih.gov/20173297/">inevitably</a> fatal. </p>
<p>Other serious infections, such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070694/">tuberculosis</a>, weren’t always fatal. Up to a <a href="https://www.biorxiv.org/content/10.1101/729426v1.full.pdf">half</a> of people died within a year with the most severe forms, but some people recovered without treatment and the remainder had ongoing chronic infection that slowly ate away at the body over many years. </p>
<p>Once we had antibiotics, the outcomes for these infections were much better.</p>
<h2>Life (and death) before antibiotics</h2>
<p>You’ve probably heard of Alexander Fleming’s accidental <a href="https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html">discovery of penicillin</a>, when fungal spores landed on a plate with bacteria left over a long weekend in 1928. </p>
<p>But the <a href="https://www.ox.ac.uk/news/science-blog/penicillin-oxford-story">first patient</a> to receive penicillin was an instructive example of the impact of treatment.
In 1941, Constable Albert Alexander had a scratch on his face that had become infected. </p>
<p>He was hospitalised but despite various treatments, the infection progressed to involve his head. This required removing one of his eyes.</p>
<figure class="align-center ">
<img alt="Old hospital room" src="https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In 1941, Albert Alexander was hospitalised with a severe infection.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/furniture-and-fixtures-in-a-hospital-room-13083355/">Jonathan Borba/Pexels</a></span>
</figcaption>
</figure>
<p>Howard Florey, the Australian pharmacologist then working in Oxford, was concerned penicillin could be toxic in humans. Therefore, he felt it was only ethical to give this new drug to a patient in a desperate condition. </p>
<p>Constable Alexander was given the available dose of penicillin. Within the first day, his condition had started to improve. </p>
<p>But back then, penicillin was difficult to produce. One way of extending the limited supply was to “recycle” penicillin that was excreted in the patient’s urine. Despite this, supplies ran out by the fifth day of Alexander’s treatment. </p>
<p>Without further treatment, the infection again took hold. Constable Alexander eventually died a month later.</p>
<p>We now face a world where we are potentially running out of antibiotics – not because of difficulties manufacturing them, but because they’re losing their effectiveness.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>What do we use antibiotics for?</h2>
<p>We currently use antibiotics in humans and animals for a variety of reasons. Antibiotics reduce the duration of illness and the chance of death from infection. They also prevent infections in people who are at high risk, such as patients undergoing surgery and those with weakened immune systems. </p>
<p>But antibiotics aren’t always used appropriately. <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30084-0/fulltext">Studies</a> consistently show a dose or two will adequately prevent infections after surgery, but antibiotics are <a href="https://irp.cdn-website.com/d820f98f/files/uploaded/surgical-prophylaxis-prescribing-in-australian-hospitals-results-of-the-2020-surgical-national-antimicrobial-prescribing-survey.pdf">often</a> continued for several days unnecessarily. And sometimes we use the wrong type of antibiotic. </p>
<p><a href="https://irp.cdn-website.com/d820f98f/files/uploaded/antimicrobial-prescribing-practice-in-australian-hospitals-results-of-the-2020-hospital-national-antimicrobial-prescribing-survey.pdf">Surveys</a> have found 22% of antimicrobial use in hospitals is inappropriate. </p>
<figure class="align-center ">
<img alt="Pharmacist looks at label on medicine box" src="https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibiotics are used for longer than needed and sometimes the wrong type is used.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-white-dress-shirt-and-black-pants-standing-near-brown-wooden-shelf-fTQHPb6r4wQ">National Cancer Institute/Unsplash</a></span>
</figcaption>
</figure>
<p>In some situations, this is understandable. Infections in different body sites are usually due to different types of bacteria. When the diagnosis isn’t certain, we often <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/resp.13334">err</a> on the side of caution by giving broad spectrum antibiotics to make sure we have active treatments for all possible infections, until further information becomes available.</p>
<p>In other situations, there is a degree of inertia. If the patient is improving, doctors tend to simply continue the same treatment, rather than change to more appropriate choice. </p>
<p>In general practice, the issue of diagnostic uncertainty and therapeutic inertia are often magnified. Patients who recover after starting antibiotics don’t usually require tests or come back for review, so there is no easy way of knowing if the antibiotic was actually required. </p>
<p>Antibiotic prescribing can be more complex again if <a href="https://www.mja.com.au/journal/2014/201/2/antibiotic-prescribing-practice-residential-aged-care-facilities-health-care">patients</a> are expecting “a pill for every ill”. While doctors are generally good at educating patients when antibiotics are not likely to work (for example, for viral infections), without confirmatory tests there can always be a lingering doubt in the minds of both doctors and patients. Or sometimes the patient goes elsewhere to find a prescription. </p>
<p>For other infections, resistance can develop if treatments aren’t given for long enough. This is particularly the <a href="https://pubmed.ncbi.nlm.nih.gov/11971765/">case</a> for tuberculosis, caused by a slow growing bacterium that requires a particularly long course of antibiotics to cure. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/tuberculosis-isnt-just-a-historical-disease-heres-how-it-spreads-and-who-is-at-risk-215154">Tuberculosis isn't just a historical disease. Here's how it spreads and who is at risk</a>
</strong>
</em>
</p>
<hr>
<p>As in humans, antibiotics are also used to prevent and treat infections in animals. However, a proportion of antibiotics are used for growth promotion. In Australia, an <a href="https://www.mja.com.au/journal/2019/211/4/antibiotic-use-animals-and-humans-australia">estimated</a> 60% of antibiotics were used in animals between 2005-2010, despite growth-promotion being phased out.</p>
<h2>Why is overuse a problem?</h2>
<p>Bacteria become resistant to the effect of antibiotics through natural selection – those that survive exposure to antibiotics are the strains that have a mechanism to evade their effects. </p>
<p>For example, antibiotics are sometimes given to <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30279-2/fulltext">prevent</a> recurrent urinary tract infections, but a consequence, any infection that does <a href="https://academic.oup.com/cid/article/73/3/e782/6141409">develop</a> tends to be with resistant bacteria.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rising-antibiotic-resistance-in-utis-could-cost-australia-1-6-billion-a-year-by-2030-heres-how-to-curb-it-149543">Rising antibiotic resistance in UTIs could cost Australia $1.6 billion a year by 2030. Here's how to curb it</a>
</strong>
</em>
</p>
<hr>
<p>When resistance to the commonly used first-line antibiotics occurs, we often need to reach deeper into the bag to find other effective treatments. </p>
<p>Some of these last-line antibiotics are those that had been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202707/">superseded</a> because they had serious side effects or couldn’t be given conveniently as tablets. </p>
<p>New drugs for some bacteria have been developed, but many are much more <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955006/">expensive</a> than older ones. </p>
<h2>Treating antibiotics as a valuable resource</h2>
<p>The concept of antibiotics as a valuable resource has led to the <a href="https://pubmed.ncbi.nlm.nih.gov/8856755/">concept</a> of “antimicrobial stewardship”, with programs to promote the responsible use of antibiotics. It’s a similar concept to environmental stewardship to prevent climate change and environmental degradation. </p>
<p>Antibiotics are a rare class of medication where treatment of one patient can potentially affect the outcome of other patients, through the transmission of antibiotic resistant bacteria. Therefore, like efforts to combat climate change, antibiotic stewardship relies on changing individual actions to benefit the broader community.</p>
<figure class="align-center ">
<img alt="Surgeon ties her mask" src="https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antimicrobial stewardship relies on individuals making decisions for the greater good.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-teal-shirt-wearing-white-mask-8hHxO3iYuU0">SJ Objio/Unsplash</a></span>
</figcaption>
</figure>
<p>Like climate change, antibiotic resistance is a complex problem when seen in a broader context. Studies have linked resistance to the values and priorities <a href="https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(18)30186-4/fulltext">of governments</a> such as corruption and infrastructure, including the availability of electricity and public services. This highlights that there are broader “causes of the causes”, such as public spending on sanitation and health care. </p>
<p>Other <a href="https://academic.oup.com/jac/article/74/9/2803/5512029?login=true">studies</a> have suggested individuals need to be considered within the broader social and institutional influences on prescribing behaviour. Like all human behaviour, antibiotic prescribing is complicated, and factors like what doctors feel is “normal” prescribing, whether junior staff feel they can challenge senior doctors, and even their <a href="https://www.nytimes.com/2016/10/07/upshot/your-surgeon-is-probably-a-republican-your-psychiatrist-probably-a-democrat.html">political views</a> may be important. </p>
<p>There are also issues with the <a href="https://www.cambridge.org/core/journals/international-journal-of-technology-assessment-in-health-care/article/value-assessment-of-antimicrobials-and-the-implications-for-development-access-and-funding-of-effective-treatments-australian-stakeholder-perspective/D45758CFB95520DA4FF06E46135E0628">economic model</a> for developing new antibiotics. When a new antibiotic is first approved for use, the first reaction for prescribers is not to use it, whether to ensure it retains its effectiveness or because it is often very expensive. </p>
<p>However, this doesn’t really <a href="https://academic.oup.com/cid/article/50/8/1081/449089?login=true">encourage</a> the development of new antibiotics, particularly when pharma research and development budgets can easily be diverted to developing drugs for conditions patients take for years, rather than a few days. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-need-to-change-how-antibiotics-target-bugs-if-we-want-them-to-keep-working-183135">We need to change how antibiotics target bugs if we want them to keep working</a>
</strong>
</em>
</p>
<hr>
<h2>The slow moving pandemic of resistance</h2>
<blockquote>
<p>If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine
– <a href="https://amr-review.org/">David Cameron</a>, former UK Prime Minister </p>
</blockquote>
<p>Antibiotic resistance is already a problem. Almost all infectious diseases physicians have had the dreaded call about patients with infections that were essentially untreatable, or where they had to scramble to find supplies of long-forgotten last-line antibiotics. </p>
<p>There are already hospitals in some parts of the world that have had to carefully <a href="https://www.reactgroup.org/news-and-views/news-and-opinions/year-2022/the-impact-of-antibiotic-resistance-on-cancer-treatment-especially-in-low-and-middle-income-countries-and-the-way-forward/">consider</a> whether it’s still viable to treat cancers, because of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276316/">high risk</a> of infections with antibiotic-resistant bacteria. </p>
<p>A global <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">study</a> estimated that in 2019, almost 5 million deaths occurred with an infection involving antibiotic-resistant bacteria. Some 1.3 million would not have occurred if the bacteria were not resistant. </p>
<p>The UK’s 2014 <a href="https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf">O'Neill report</a> predicted deaths from antimicrobial resistance could rise to 10 million deaths each year, and cost 2-3.5% of global GDP, by 2050 based on trends at that time. </p>
<h2>What can we do about it?</h2>
<p>There is a lot we can do to prevent antibiotic resistance. We can:</p>
<ul>
<li><p><a href="https://www.marketingmag.com.au/news/film-picking-gonorrhoea-wins-tropfest-prize/">raise</a> <a href="https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7258-3">awareness</a> that many infections will get better by themselves, and don’t necessarily need antibiotics </p></li>
<li><p>use the antibiotics we have more appropriately and for as short a time as possible, supported by co-ordinated clinical and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437704/">public policy</a>, and <a href="https://www.amr.gov.au/">national</a> <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00796-4/fulltext">oversight</a> </p></li>
<li><p><a href="https://www.safetyandquality.gov.au/our-work/antimicrobial-resistance/antimicrobial-use-and-resistance-australia-surveillance-system/about-aura-surveillance-system">monitor</a> for infections due to resistant bacterial to inform control policies </p></li>
<li><p>reduce the inappropriate use of antibiotics in animals, such as <a href="https://nam.edu/antibiotic-resistance-in-humans-and-animals/">growth promotion</a> </p></li>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/11971765/">reduce</a> cross-transmission of resistant organisms in hospitals and in the community </p></li>
<li><p>prevent infections by other means, such as clean water, <a href="https://apps.who.int/iris/bitstream/handle/10665/204948/WHO_FWC_WSH_14.7_eng.pdf">sanitation</a>, hygiene and <a href="https://www.who.int/teams/immunization-vaccines-and-biologicals/product-and-delivery-research/anti-microbial-resistance">vaccines</a> </p></li>
<li><p>continue developing new antibiotics and alternatives to antibiotics and ensure the right <a href="https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00124-2/fulltext#:%7E:text=We%20consider%20four%20incentive%20options,exclusivity%20extensions%2C%20and%20milestone%20payments.">incentives</a> are in place to encourage a continuous pipeline of new drugs.</p></li>
</ul>
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<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213450/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Cheng receives funding from the Australian Government and the National Health and Medical Research Council. He is affiliated with the Centre to Impact Antimicrobial Resistance at Monash University. </span></em></p>Antibiotics have been around for less than a century. But as resistant bacteria become increasingly difficult to treat, we risk a greater number of deaths from infections.Allen Cheng, Professor of Infectious Diseases, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134512023-11-07T19:35:15Z2023-11-07T19:35:15ZHow do bacteria actually become resistant to antibiotics?<figure><img src="https://images.theconversation.com/files/555508/original/file-20231024-24-2win4c.jpg?ixlib=rb-1.1.0&rect=0%2C817%2C5928%2C3745&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/a-person-holding-a-round-object-in-their-hands-y--8fqaK1kY">CDC/Unsplash</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>“What doesn’t kill me makes me stronger”, originally coined by <a href="https://www.dictionary.com/e/slang/what-doesnt-kill-you-makes-you-stronger/">Friedrich Nietzsche in 1888</a>, is a perfect description of how bacteria develop <a href="https://www.nps.org.au/consumers/antibiotics-explained#what-is-antibiotic-resistance?">antibiotic resistance</a>. </p>
<p>Contrary to a common belief, antibiotic resistance <a href="https://www.cdc.gov/antibiotic-use/images/Infographic-AR-bacteria.jpg">is not</a> about your body becoming resistant to antibiotics. </p>
<p>Resistance arises when bacteria are exposed to levels of antibiotics that don’t immediately kill them. They develop defences that prevent the same antibiotic from harming them in the future, even at higher doses.</p>
<h2>How bacteria adapt</h2>
<p>The ability for bacteria to adapt lies in part with their astonishing rate of reproduction. Some species, such as <em>Escherichia coli</em>, can <a href="https://www.youtube.com/watch?v=gEwzDydciWc">replicate</a> as quickly as every 20 minutes, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015860/">depending on the environment</a>. One bacterium can become more than 68 billion bacteria in 12 hours.</p>
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Read more:
<a href="https://theconversation.com/im-a-microbiologist-and-heres-what-and-where-i-never-eat-213404">I'm a microbiologist and here's what (and where) I never eat</a>
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<p>However, bacteria don’t faithfully reproduce their genetic code, and mutations can slip in every generation. </p>
<p>While most changes are bad, sometimes they can help the bacteria grow in the presence of an antibiotic. This “new and improved” population <a href="https://www.cdc.gov/antibiotic-use/images/Infographic-how-AR-happens.jpg">quickly takes over</a>.</p>
<p>Additional mutations enable survival at even higher antibiotic concentrations.</p>
<p>This evolution of resistance can be seen by growing bacteria on a large agar plate (a nutrient support that bacteria like to grow on) with zones of increasing antibiotic levels. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/plVk4NVIUh8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Watch how bacteria develop resistance to extremely high concentrations of antibiotics (Harvard Medical School).</span></figcaption>
</figure>
<p>Growth is halted when they first encounter the next zone, but once they have developed resistance they quickly expand until they reach the next region with more antibiotic. </p>
<p>Bacteria in your body can easily develop resistance in a similar manner during the typical seven- to ten-day course of antibiotic treatment.</p>
<h2>They also exchange genetic material</h2>
<p>The other key mechanism enabling bacterial resistance is the <a href="https://www.cdc.gov/drugresistance/pdf/threats-report/How-AR-Moves-508.pdf">exchange of genetic information</a> between bacteria. </p>
<p>In addition to the main chunk of DNA that encodes the bacterial genome, bacteria can host circular DNA snippets called plasmids. These plasmids are <a href="https://asm.org/Articles/2023/January/Plasmids-and-the-Spread-of-Antibiotic-Resistance-G">readily exchanged between bacteria</a>, including different species.</p>
<p>Plasmid exchange usually occurs by direct physical contact between bacteria. Bacteria are promiscuous, so this can happen a lot! Once inside a bacteria, plasmids can be passed down to the next generation. </p>
<p>Unfortunately, plasmids are <a href="https://www.annualreviews.org/doi/10.1146/annurev.biochem.78.082907.145923?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed">particularly good</a> at encoding multiple resistance genes.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rising-antibiotic-resistance-in-utis-could-cost-australia-1-6-billion-a-year-by-2030-heres-how-to-curb-it-149543">Rising antibiotic resistance in UTIs could cost Australia $1.6 billion a year by 2030. Here's how to curb it</a>
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</em>
</p>
<hr>
<h2>4 ways bacteria resist</h2>
<p>Bacteria develop resistance to antibiotic treatment using four main methods:</p>
<p><strong>1) Keep the antibiotic out.</strong> Bacteria are good at keeping unwanted molecules from getting inside. </p>
<p>Gram-positive bacteria like <em>Staphylococcus aureus</em> have a thick cell wall enclosing a lipid membrane. Gram-negative bacteria, such as <em>E. coli</em>, are more difficult to kill as they have an additional outer membrane that acts as an extra barrier. </p>
<p>Bacteria are able to bring in the things they need to survive through these cell surfaces. Antibiotics can hijack these entry routes, but bacteria can modify the cell wall, cell membrane and entry proteins to block antibiotic penetration.</p>
<p>For example, bacteria <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149586/">increase the thickness</a> of the cell wall to resist antibiotics like vancomycin.</p>
<figure class="align-center ">
<img alt="Lab worker puts dropper into petri dish" src="https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bacteria are good at keeping antibiotics out.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/man-doing-a-sample-test-in-the-laboratory-4033148/">Edward Jenner/Pexels</a></span>
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</figure>
<p><strong>2. Expel the antibiotic if it gets in</strong>. Bacteria have machinery known as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032748/">efflux pumps</a>, which regurgitate unwanted molecules from within the bacteria. </p>
<p>Bacteria can alter the pump so it is more effective at removing the antibiotic, or they can simply make more pumps. </p>
<p>Resistance to macrolide antibiotics like erythromycin often involves <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1251515/">the production of more efflux pumps</a>.</p>
<p><strong>3) Alter the antibiotic target.</strong> Antibiotics, like most other drugs, generally work by blocking the function of important enzymes within the bacteria. They specifically bind to the target like a key in a lock. </p>
<p>If bacteria alter the target shape by changing the DNA/protein sequence, the antibiotic (key) can no longer bind to its target (lock). </p>
<p>Resistance to a class of antibiotics known as fluoroquinolones (which includes ciprofloxacin) often occurs due to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114060/">mutations of the enzyme targets</a>.</p>
<p><strong>4) Destroy or modify the antibiotic.</strong> Bacteria developed resistance to the original antibiotic, penicillin, by producing a protein that breaks apart the penicillin warhead. </p>
<p>These enzymes have evolved to keep pace with even the most recent new and improved penicillin-like antibiotics. </p>
<p>In response, drug developers <a href="https://www.drugs.com/drug-class/beta-lactamase-inhibitors.html">have created</a> molecules that specifically stop the enzyme from working, and dose these in combination with the antibiotic. </p>
<p>Another example of antibiotic modification is shown by resistance to a class of antibiotics called aminoglycosides. In this case, different types of enzymes <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752126/">chemically modify</a> the structure of the aminoglycoside, such as the antibiotic tobramycin. Now, the key has been filed so that it no longer fits the lock.</p>
<figure class="align-center ">
<img alt="Person holds three antibiotic capsules" src="https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bacteria use multiple methods to attack antibiotics.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/three-capsules-on-persons-palm-U31rRVKYL_M">Mark Fletcher/Unsplash</a></span>
</figcaption>
</figure>
<h2>Bacteria vs antibiotics</h2>
<p>While bacteria have developed mechanisms to resist antibiotics, these adaptations can come at a “fitness” cost. Bacteria may grow more slowly, or can be killed more easily by another antibiotic. </p>
<p>This has led to the concept of “<a href="https://academic.oup.com/mbe/article/39/12/msac257/6884036">collateral sensitivity</a>” to prevent or overcome resistance when treating patients, by using pairs of antibiotics. Resistance to the first antibiotic increases susceptibility to the second, and vice versa.</p>
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<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
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<p>In some cases, the “fitness costs” (energy and materials expended to maintain resistance) mean that resistance genes can be present, but they are not activated until exposed to an antibiotic. This makes it difficult to predict bacterial resistance by just looking at their genetic makeup. </p>
<p>Bacteria may get “stronger,” but they are not yet invincible. We need to take action before antibiotic resistance returns us to a pre-antibiotic era.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213451/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Blaskovich receives funding from a range of government, not-for-profit and commercial organisations for research into antibiotic discovery and development. He is affiliated with AAMRNet (Australian Antimicrobial Resistance Network), an organisation promoting improved care and development of antibiotics and antibiotic alternatives.</span></em></p>Resistance arises when bacteria are exposed to levels of antibiotics that don’t immediately kill them. Here’s how.Mark Blaskovich, Professor, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2113022023-10-17T16:42:46Z2023-10-17T16:42:46ZOnly 1% of chemical compounds have been discovered – here’s how we search for others that could change the world<figure><img src="https://images.theconversation.com/files/553049/original/file-20231010-21-ljmz9o.jpg?ixlib=rb-1.1.0&rect=49%2C74%2C5450%2C3586&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/chemical-tube-reaction-formula-light-598653854">Garsya/Shutterstock</a></span></figcaption></figure><p>The universe is flooded with billions of chemicals, each a tiny pinprick of potential. And we’ve only identified <a href="https://www.eurekalert.org/news-releases/993593">1% of them</a>. Scientists believe undiscovered chemical compounds could <a href="https://www.sciencedaily.com/releases/2021/08/210813100255.htm">help remove greenhouse gases</a>, or trigger a medical breakthrough much like penicillin did. </p>
<p>But let’s just get this out there first: it’s not that chemists aren’t curious. Since Russian chemist <a href="https://www.britannica.com/biography/Dmitri-Mendeleev">Dmitri Mendeleev</a> invented the <a href="https://www.britannica.com/science/periodic-table">periodic table of elements</a> in 1869, which is basically a chemist’s box of Lego, scientists have been discovering the chemicals that helped define the modern world. We needed nuclear fusion (firing atoms at each other at the speed of light) to make the last handful of elements. Element 117, <a href="https://www.rsc.org/periodic-table/element/117/tennessine">tennessine</a>, was synthesised in 2010 in this way. </p>
<p>But to understand the full scale of the chemical universe, you need to understand <a href="https://www.britannica.com/science/chemical-compound">chemical compounds</a> too. Some occur naturally – water, of course, is made of hydrogen and oxygen. Others, such as <a href="https://www.britannica.com/science/nylon">nylon</a>, were discovered in lab experiments and are manufactured in factories. </p>
<p><a href="https://www.bbc.co.uk/bitesize/topics/zstp34j/articles/zc86m39#:%7E:text=An%20element%20is%20a%20pure,There%20are%20118%20different%20elements.">Elements are made of one type of atom</a>, and <a href="https://www.livescience.com/37206-atom-definition.html">atoms are made of even tinier particles</a> including electrons and protons. All chemical compounds are made of two or more atoms. Although it’s possible there are undiscovered elements left to find, <a href="https://www.chemistryworld.com/news/beyond-element-118-the-next-row-of-the-periodic-table/9400.article">it’s unlikely</a>. So, how many <a href="https://www.wordnik.com/words/chemical%20compound">chemical compounds</a> can we make with the 118 different sorts of element Lego blocks we currently know?</p>
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<h2>Big numbers</h2>
<p>We can start by making all the <a href="https://www.britannica.com/science/diatomic-molecule">two-atom compounds</a>. There are lots of these: N<sub>2</sub> (nitrogen) and O<sub>2</sub> (oxygen) together make up 99% of our air. It would probably take a chemist about a year to make one compound and there are 6,903 two-atom compounds in theory. So that’s a village of chemists working a year just to make every possible two-atom compound. </p>
<p>There about 1.6 million three-atom compounds like H₂0 (water) and C0₂ (carbon dioxide), which is the population of Birmingham and Edinburgh combined. Once we reach four- and five-atom compounds, we would need everyone on Earth to make three compounds each. And to make <a href="https://sciencenotes.org/how-many-atoms-are-in-the-world/">all these chemical compounds</a>, we’d also need to recycle all the materials in the universe several times over. </p>
<p>But this is a simplification, of course. Things such as the structure of a compound and its stability can make it more complex and difficult to make.</p>
<p>The biggest chemical compound that has been made so far was <a href="https://pubs.acs.org/doi/full/10.1021/om900079y">made in 2009</a> and has nearly 3 million atoms. We’re not sure what it does yet, but <a href="https://doi.org/10.1039/C9TB02289A">similar compounds</a> are used to protect cancer drugs in the body until they get to the right place.</p>
<p>But wait, chemistry has rules! </p>
<h2>Surely not all those compounds are possible?</h2>
<p>It’s true there are rules – but they are kind of bendy, which creates more possibilities for chemical compounds. </p>
<p>Even the solitary “<a href="https://en.wikipedia.org/wiki/Noble_gas">noble gases</a>” (including neon, argon and xenon and helium), which tend to not bind with anything, <a href="https://www.aanda.org/articles/aa/abs/2014/06/aa23727-14/aa23727-14.html">sometimes form compounds</a>. Argon hydride, ArH<sup>+</sup> does not exist naturally on Earth but has been found in space. Scientists have been able to make synthetic versions in laboratories that replicate deep space conditions. So, if you include extreme environments in your calculations, the number of possible compounds increases. </p>
<p>Carbon normally likes being attached to between one and four other atoms, but very occasionally, for short periods of time, <a href="https://en.wikipedia.org/wiki/Methanium">five is possible</a>. Imagine a bus with a maximum capacity of four. The bus is at the stop, and people are getting on and off; while people are moving, briefly, you can have more than four people actually on the bus.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/confessions-of-a-chemist-i-make-molecules-that-shouldnt-exist-53326">Confessions of a chemist: I make molecules that shouldn't exist</a>
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</em>
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<p>Some chemists spend their entire careers trying to make compounds that, according to the chemistry rulebook, shouldn’t exist. Sometimes they are successful.</p>
<p>Another question scientists have to grapple with is whether the compound they want can only exist in space or extreme environments – think of the immense heat and pressure found at <a href="https://oceanservice.noaa.gov/facts/vents.html">hydrothermal vents</a>, which are like geysers but on the ocean floor. </p>
<h2>How scientists search for new compounds</h2>
<p>Often the answer is to search for compounds that are related to ones that are already known. There are two main ways to do this. One is taking a known compound and changing it a bit – by adding, deleting or swapping some atoms. Another is taking a known chemical reaction and using new starting materials. This is when the method of creation is the same but the products may be quite different. Both of these methods are ways of searching for <em>known unknowns</em>. </p>
<p>Coming back to Lego, it’s like making a house, then a slightly different house, or buying new bricks and adding a second storey. A lot of chemists <a href="https://en.wikipedia.org/wiki/Mary_Elliott_Hill">spend their careers</a> exploring one of these chemical houses.</p>
<p>But how would we search for truly new chemistry – that is, <em>unknown unknowns</em>? </p>
<p>One way chemists learn about new compounds is to look at the natural world. Penicillin was found this way in 1928, when Alexander Fleming observed that mould in his petri dishes <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">prevented the growth of bacteria</a>.</p>
<p>Over a decade later, in 1939, <a href="https://www.nobelprize.org/prizes/medicine/1945/florey/biographical/">Howard Florey</a> worked out how to grow penicillin in useful amounts, still using mould. But it took even longer, until 1945, for <a href="https://www.nobelprize.org/prizes/chemistry/1964/hodgkin/biographical/">Dorothy Crowfoot Hodgkin</a> to identify penicillin’s chemical structure. </p>
<p>That’s important because part of penicillin’s structure contains atoms arranged in a square, which is an unusual chemical arrangement that few chemists would guess, and is difficult to make. Understanding penicillin’s structure meant we knew what it looked like and could search for its chemical cousins. If you’re allergic to penicillin and have needed an alternative antibiotic, you have Crowfoot Hodgkin to thank. </p>
<p>Nowadays, it’s a lot easier to determine the structure of new compounds. The X-ray technique that Crowfoot Hodgkin invented on her way to identifying penicillin’s structure is still used worldwide to study compounds. And the same MRI technique that hospitals use to diagnose disease can <a href="https://www.acs.org/education/whatischemistry/landmarks/mri.html">also be used on chemical compounds</a> to work out their structure.</p>
<p>But even if a chemist guessed a completely new structure unrelated to any compound known on Earth, they’d still have to make it, which is the hard part. Figuring out that a chemical compound could exist does not tell you how it’s structured or what conditions you need to make it.</p>
<p>For many useful compounds, like <a href="https://www.nature.com/articles/ja2012126">penicillin</a>, it’s easier and cheaper to “grow” and extract them from moulds, plants or insects. Thus the scientists searching for new chemistry still often look for inspiration in the tiniest corners of the world around us.</p><img src="https://counter.theconversation.com/content/211302/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Addicoat receives funding from EPSRC and the Royal Society. </span></em></p>The limitless world of chemistry and how researchers investigate it.Matthew Addicoat, Senior Lecturer in Functional Materials, Nottingham Trent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2146712023-10-04T14:15:47Z2023-10-04T14:15:47ZMost people who think they are allergic to penicillin aren’t<figure><img src="https://images.theconversation.com/files/552043/original/file-20231004-17-iavmz9.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5190%2C3602&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/boston-massachusetts-united-states-december-2-1581332569">Michael Moloney/Shutterstock</a></span></figcaption></figure><p>About <a href="https://www.rpharms.com/about-us/news/details/millions-mistakenly-think-they-are-allergic-to-penicillin-#:%7E:text=Around%206%25%20of%20people%20have,to%20it%20when%20fully%20assessed.">6% of people in the UK</a> are wrongly labelled on their medical records as being allergic to penicillin, the Royal Pharmaceutical Society has warned.</p>
<p>This figure is concerning because being labelled as allergic to this class of highly effective antibiotics is associated with an extra <a href="https://academic.oup.com/jac/article/74/7/2075/5443267">six deaths per 1,000 patients</a> a year after being treated for an infection. If patients received the right antibiotic for their infection, many lives could be saved.</p>
<p>Allergies vary between us, but someone allergic to penicillin typically develops a rash, itching and swelling. Their throat may become tight and breathing difficult.</p>
<p>Diagnosing a penicillin allergy in an unwell person can be tricky. Typically, it is made when using penicillin to treat a feverish child with signs of an infected ear or throat. If they develop a rash, to be safe, the doctor may note on their medical records that they are allergic to the antibiotics. </p>
<p>This is done because someone allergic to penicillin typically responds badly to the next dose of penicillin, which can include the potentially lethal condition known as <a href="https://www.nhs.uk/conditions/anaphylaxis/">anaphylaxis</a>.</p>
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<figcaption><span class="caption">How to spot anaphylaxis.</span></figcaption>
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<p>This precautionary and often spurious label of “penicillin allergy” is highly likely to follow people through childhood and into their various medical records, without review and checking. These people continue to avoid penicillin treatments. So a great deal hinges on that rash.</p>
<p>However, rashes in people with a fever have many possible causes. A host of enteroviruses, to take one group of germs, give rise to rashes during an illness. And the Epstein-Barr virus will <a href="https://pubmed.ncbi.nlm.nih.gov/32346863/">often cause a rash</a> if a patient is treated with amoxicillin (an antibiotic from the penicillin family). And not all penicillin-induced rashes are allergic – they are just side-effects of the medicine. </p>
<p>Other symptoms such as diarrhoea or vomiting that might develop during a course of penicillin may represent an adverse reaction to the antibiotic, but not an allergy with any risk of future anaphylaxis. Some studies suggest that patients who once suffered an actual allergic reaction to penicillin may <a href="https://pubmed.ncbi.nlm.nih.gov/36916097/">lose this reaction over time</a>, so it is unclear if penicillin allergy is for life. </p>
<p>Those with “penicillin allergy” on their medical records have <a href="https://pubmed.ncbi.nlm.nih.gov/37666558/">worse health outcomes</a> and increased rates of <a href="https://pubmed.ncbi.nlm.nih.gov/30644987/">antimicrobial resistance</a> when treated with alternative, broad-spectrum antibiotics (broad-spectrum antibiotics kill a wide range of bacteria, not just the one suspected of causing infection).</p>
<p>Doctors <a href="https://pubmed.ncbi.nlm.nih.gov/36948494/">reporting from Pennsylvania in the US</a> this summer compared over 3,700 children and adolescents with pneumonia who had a penicillin allergy label with a similar number of those without. Those with the label had higher rates of hospitalisation, respiratory failure, intensive care treatment, adverse drug reactions and infection with <em>Clostridium difficile</em> (a type of bacteria that can cause a bowel infection). </p>
<p>Other studies have noted <a href="https://pubmed.ncbi.nlm.nih.gov/37153141/">increased risks of infections</a> following surgery, readmission to hospital, and <a href="https://pubmed.ncbi.nlm.nih.gov/33849960/">infection with the MRSA superbug</a> in “penicillin allergy” patients. These consequences are costly to patients, their families and health services. </p>
<h2>Find out if you are allergic</h2>
<p>A penicillin allergy can be confirmed by collecting exact information about how this developed, and sometimes skin prick tests or taking a very small dose of penicillin by mouth if required. GPs, nurses and pharmacists are being tasked to check drug allergy labels in medical records. Large surveys show these methods allow almost everyone to take this family of antibiotics safely.</p>
<p>Penicillins are routinely used as part of the treatment <a href="https://pubmed.ncbi.nlm.nih.gov/37110283/">in people with sickle cell anaemia</a>. They take the antibiotic twice a day, for life. Sickle cell anaemia is a common genetic condition. Over 12,000 people are followed regularly in the UK, yet <a href="https://pubmed.ncbi.nlm.nih.gov/11849580/">penicillin allergy in this group is rare</a>. This should provide reassurance about penicillin safety, placing allergies into a more reasonable perspective.</p>
<p>Accurate, up-to-date information is needed to support your health and that of others. If you think you have a penicillin allergy it would be wise to discuss and confirm this with your doctor. Removing this label might be of great benefit to you and others.</p><img src="https://counter.theconversation.com/content/214671/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colin Michie does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Around 90% of people who have been incorrectly told by their doctor that they are allergic to penicillin.Colin Michie, Deputy Lead, School of Medicine, University of Central LancashireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2147702023-10-03T00:31:22Z2023-10-03T00:31:22ZTenacious curiosity in the lab can lead to a Nobel Prize – mRNA research exemplifies the unpredictable value of basic scientific research<figure><img src="https://images.theconversation.com/files/551551/original/file-20231002-25-ii4mxj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2100%2C1427&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Basic research often involves lab work that won't be appreciated until decades down the line.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pcr-diagnostics-kit-royalty-free-image/1285418766">Sebastian Condrea/Moment via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://www.nobelprize.org/prizes/medicine/2023/press-release/">2023 Nobel Prize in physiology or medicine</a> will go to Katalin Karikó and Drew Weissman for their discovery that modifying <a href="https://www.genome.gov/genetics-glossary/messenger-rna">mRNA</a> – a form of genetic material your body uses to produce proteins – could reduce unwanted inflammatory responses and allow it to be delivered into cells. While the impact of their findings may not have been apparent at the time of their breakthrough over a decade ago, their work paved the way for the development of the <a href="https://theconversation.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases-170772">Pfizer-BioNTech and Moderna COVID-19 vaccines</a>, as well as many other therapeutic applications currently in development. The <a href="https://www.nobelprize.org/prizes/physics/2023/summary/">2023 Nobel Prize in physics</a> likewise will go to a team of scientists who used lasers to clarify the behavior of electrons, and many prior Nobels have honored basic research.</em></p>
<p><em>We asked André O. Hudson, a <a href="https://scholar.google.com/citations?user=zLwzHqcAAAAJ&hl=en">biochemist and microbiologist</a> at the Rochester Institute of Technology, to explain how basic research like that of this year’s Nobel Prize winners provides the foundations for science – even when its far-reaching effects won’t be felt until years later.</em></p>
<h2>What is basic science?</h2>
<p><a href="https://www.niaid.nih.gov/grants-contracts/basic-research-definition">Basic research</a>, sometimes called fundamental research, is a type of investigation with the overarching goal of understanding natural phenomena like how cells work or how birds can fly. Scientists are asking the fundamental questions of how, why, when, where and if in order to bridge a gap in curiosity and understanding about the natural world.</p>
<p>Researchers sometimes conduct basic research with the hope of eventually developing a technology or drug based on that work. But what many scientists typically do in academia is ask fundamental questions with answers that may or may not ever lead to practical applications.</p>
<p>Humans, and the animal kingdom as a whole, are <a href="https://www.cell.com/current-biology/pdf/S0960-9822(13)00265-0.pdf">wired to be curious</a>. Basic research scratches that itch.</p>
<h2>What are some basic science discoveries that went on to have a big influence on medicine?</h2>
<p>The <a href="https://www.nobelprize.org/prizes/medicine/2023/press-release/">2023 Nobel Prize in physiology or medicine</a> acknowledges basic science work done in the early 2000s. Karikó and Weissman’s discovery about modifying mRNA to reduce the body’s inflammatory response to it allowed other researchers to leverage it to make improved vaccines.</p>
<p>Another example is the <a href="https://theconversation.com/guns-not-roses-heres-the-true-story-of-penicillins-first-patient-178463">discovery of antibiotics</a>, which was based on an unexpected observation. In the late 1920s, the microbiologist Alexander Fleming was growing a species of bacteria in his lab and found that his Petri dish was accidentally contaminated with the fungus <em>Penicillium notatum</em>. He noticed that wherever the fungus was growing, it impeded or inhibited the growth of the bacteria. He wondered why that was happening and subsequently went on to isolate penicillin, which was approved for medical use in the early 1940s.</p>
<p>This work fed into more questions that ushered in the age of antibiotics. The 1952 Nobel Prize in physiology or medicine was awarded to Selman Waksman for his <a href="https://www.nobelprize.org/prizes/medicine/1952/summary/">discovery of streptomycin</a>, the first antibiotic to treat tuberculosis.</p>
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<figcaption><span class="caption">Penicillin was discovered by accident.</span></figcaption>
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<p>Basic research often involves seeing something surprising, wanting to understand why and deciding to investigate further. Early discoveries start from a basic observation, asking the simple question of “How?” Only later are they parlayed into a medical technology that helps humanity.</p>
<h2>Why does it take so long to get from curiosity-driven basic science to a new product or technology?</h2>
<p>The mRNA modification discovery could be considered to be on a relatively fast track from basic science to application. Less than 15 years passed between Karikó and Weissman’s findings and the COVID-19 vaccines. The importance of their discovery came to the forefront with the pandemic and the <a href="https://www.commonwealthfund.org/blog/2022/two-years-covid-vaccines-prevented-millions-deaths-hospitalizations">millions of lives</a> they saved.</p>
<p>Most basic research won’t reach the market until <a href="https://doi.org/10.1126/scitranslmed.aaa0599">several decades</a> after its initial publication in a science journal. One reason is because it depends on need. For example, <a href="https://www.fda.gov/drugs/information-consumers-and-patients-drugs/orphan-products-hope-people-rare-diseases">orphan diseases</a> that affect only a small number of people will get less attention and funding than conditions that are ubiquitous in a population, like cancer or diabetes. Companies don’t want to spend billions of dollars developing a drug that will only have a small return on their investment. Likewise, because the return on investment for basic research often isn’t clear, it can be a hard sell to support financially.</p>
<p>Another reason is cultural. Scientists are trained to chase after funding and support for their work wherever they can find it. But sometimes that’s not as easy as it seems.</p>
<p>A good example of this was when the <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">human genome was first sequenced</a> in the early 2000s. A lot of people thought that having access to the full sequence would lead to treatments and cures for many different diseases. <a href="https://theconversation.com/why-sequencing-the-human-genome-failed-to-produce-big-breakthroughs-in-disease-130568">But that has not been the case</a>, because there are many nuances to translating basic research to the clinic. What works in a cell or an animal might not translate into people. There are many steps and layers in the process to get there.</p>
<h2>Why is basic science important?</h2>
<p>For me, the most critical reason is that basic research is how we <a href="https://dx.doi.org/10.1210%2Fme.2014-1343">train and mentor future scientists</a>. </p>
<p>In an academic setting, telling students “Let’s go develop an mRNA vaccine” versus “How does mRNA work in the body” influences how they approach science. How do they design experiments? Do they start the study going forward or backward? Are they argumentative or cautious in how they present their findings?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of scientist wearing nitrile gloves looking into microscope hovering over Petri dish" src="https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551554/original/file-20231002-28-a388bt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are many steps between translating findings in a lab to the clinic.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/scrutinising-a-new-sample-royalty-free-image/1206157642">Marco VDM/E+ via Getty Images</a></span>
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<p>Almost every scientist is trained under a basic research umbrella of how to ask questions and go through the scientific method. You need to understand how, when and where mRNAs are modified before you can even begin to develop an mRNA vaccine. I believe the best way to inspire future scientists is to encourage them to expand on their curiosity in order to make a difference. </p>
<p>When I was writing my dissertation, I was relying on studies that were published in the late 1800s and early 1900s. Many of these studies are still cited in scientific articles today. When researchers share their work, though it may not be today or tomorrow, or 10 to 20 years from now, it will be of use to someone else in the future. You’ll make a future scientist’s job a little bit easier, and I believe that’s a great legacy to have.</p>
<h2>What is a common misconception about basic science?</h2>
<p>Because any immediate use for basic science can be very hard to see, it’s easy to think this kind of research <a href="https://theconversation.com/funding-basic-research-plays-the-long-game-for-future-payoffs-100435">is a waste of money or time</a>. Why are scientists breeding mosquitoes in these labs? Or why are researchers studying migratory birds? The same argument has been made with astronomy. Why are we spending billions of dollars putting things into space? Why are we looking to the edge of the universe and studying stars when they are millions and billions of light years away? How does it affect us?</p>
<p>There is a need for <a href="https://doi.org/10.1073/pnas.1912436117">more scientific literacy</a> because not having it can make it difficult to understand why basic research is necessary to future breakthroughs that will have a major effect on society.</p>
<p>In the short term, the worth of basic research can be hard to see. But in the long term, history has shown that a lot of what we take for granted now, such as common medical equipment like <a href="https://www.aps.org/publications/apsnews/200111/history.cfm">X-rays</a>, <a href="https://nationalmaglab.org/magnet-academy/history-of-electricity-magnetism/pioneers/theodore-maiman/">lasers</a> and <a href="https://www.aps.org/publications/apsnews/200607/history.cfm">MRIs</a>, came from basic things people discovered in the lab. </p>
<p>And it still goes down to the fundamental questions – we’re a species that seeks answers to things we don’t know. As long as curiosity is a part of humanity, we’re always going to be seeking answers.</p><img src="https://counter.theconversation.com/content/214770/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>André O. Hudson receives funding from the National Institutes of Health. </span></em></p>The winners of the 2023 Nobel Prize in physiology or medicine made a discovery that helped create the COVID-19 vaccines. They couldn’t have anticipated the tremendous impact of their findings.André O. Hudson, Dean of the College of Science, Professor of Biochemistry, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2072862023-07-12T12:38:49Z2023-07-12T12:38:49ZStrep throat can easily be confused with throat infections caused by viruses – here are a few ways to know the difference<figure><img src="https://images.theconversation.com/files/536374/original/file-20230707-23-bxbi1g.jpg?ixlib=rb-1.1.0&rect=0%2C9%2C6640%2C4220&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Strep is most common in children between the ages of 5 and 15.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/male-pediatrician-examining-little-child-patients-royalty-free-image/1306247195?phrase=doctor+checking+for+strep&adppopup=true">aquaArts studio/E+ via Getty Images</a></span></figcaption></figure><p>“My sore throats, you know, are always worse than anybody’s.”</p>
<p>So declares Mary to Anne in “<a href="https://jasna.org/austen/works/persuasion/">Persuasion</a>,” Jane Austen’s 1817 book. Most of us can relate to this feeling. There is no such thing as “just a sore throat.” The pain, headache, fever and aches associated with a sore throat can make you feel terrible.</p>
<p>While sore throats can occur at any time of year, strep throat is <a href="https://www.cdc.gov/groupastrep/surveillance.html#">more common in the fall, winter and early spring</a>.</p>
<p>I am a <a href="https://facultyprofiles.tufts.edu/allen-shaughnessy">professor of family medicine</a>, a pharmacist and an expert on evidence-based medicine. My work involves the evaluation of research performed by others, and I have been following and analyzing research findings on strep for the past 30 years. </p>
<p>Many people incorrectly assume that all sore throats are due to strep throat, a bacterial infection of the pharynx, the middle throat area behind the nose and mouth, and patients often come to our family medicine office wanting to be checked and treated for strep with antibiotics.</p>
<p>However, neither testing nor treatment is always needed for a sore throat. Regardless of the cause, rest and pain relievers form the cornerstone of sore throat treatment.</p>
<p>Here’s some guidance on whether and when testing is necessary.</p>
<h2>Bacterial versus viral sore throats</h2>
<p>Most <a href="https://www.cdc.gov/antibiotic-use/sore-throat.html">sudden-onset sore throats</a> are caused by viruses – the same ones that cause the common cold, the seasonal flu and COVID-19. There are <a href="https://www.nih.gov/news-events/nih-research-matters/understanding-common-cold-virus#">more than 200 viruses</a> that can cause sore throat and other symptoms related to the common cold. </p>
<p>But bacteria can also be the culprits behind a sore throat. One of the most common examples is <a href="https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html#">strep throat</a>, or <a href="https://www.cdc.gov/streplab/groupa-strep/index.html">group A pharyngitis</a>.</p>
<p>Strep is caused by certain strains of <em>Streptococcus pyogenes</em> bacteria.
There are many species of strep; other common forms of strep that cause different infections in humans include “<a href="https://www.cdc.gov/groupbstrep/index.html">group B strep</a>” and “<a href="https://www.icliniq.com/articles/infectious-diseases/group-d-streptococcus-infections">group D strep</a>.” Group A strep usually lives peacefully among the many other types of bacteria growing on our skin and doesn’t cause any problems, until we get a break in the skin such as a cut or a scrape. This allows it to overwhelm the immune system’s ability to keep it in check.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A teenage girl is lying on a sofa, feeling unwell and holding a thermometer in her mouth to check her temperature." src="https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/536145/original/file-20230706-18-5qdns0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Fever, headache and confusion can be symptoms of a severe case of strep.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/sick-teenager-resting-at-home-and-monitoring-royalty-free-image/1482421648?phrase=strep+throat&adppopup=true">RealPeopleGroup/E+ via Getty Images</a></span>
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<p>Group A strep can also live in the back of the throat – up to 30% of people without any evidence of a sore throat will have <a href="https://doi.org/10.3389/fcimb.2019.00137">this strain in their throat</a>. <a href="https://www.cdc.gov/groupastrep/diseases-public/strep-throat.html#">Up to 3 in 10 children and 1 in 10 adults</a> feeling sick with a sore throat due to a virus or other cause will test <a href="https://doi.org/10.1371/journal.pntd.0006335">positive for group A strep</a>. That means that people with a sore throat caused by a virus could also be positive for strep, even if it’s not causing the symptoms.</p>
<p>Not all group A strep bacteria are the same, though. Some varieties are better at evading the immune system than others and can grow quickly. Others produce byproducts that can cause a sore throat and sometimes lead to <a href="https://www.mayoclinic.org/diseases-conditions/tonsillitis/symptoms-causes/syc-20378479">tonsillitis</a>, an infection of the tonsils, or cause ear or <a href="https://www.cdc.gov/antibiotic-use/sinus-infection.html">sinus infections</a>. </p>
<p>Still other strep strains produce a toxin that can cause a characteristic <a href="https://www.cdc.gov/groupastrep/diseases-public/scarlet-fever.html">skin rash</a> or lead to effects on the <a href="https://www.cdc.gov/groupastrep/diseases-public/rheumatic-fever.html">heart</a>, <a href="https://www.cdc.gov/groupastrep/diseases-public/post-streptococcal.html">kidneys</a> or even the <a href="https://www.nimh.nih.gov/health/publications/pandas">brain</a>. </p>
<p>Rarer still, group A strep can enter the bloodstream and cause <a href="https://www.mayoclinic.org/diseases-conditions/toxic-shock-syndrome/symptoms-causes/syc-20355384">toxic shock syndrome</a>, a life-threatening, overwhelming infection. These latter conditions are examples of invasive strep, meaning that the infection is in parts of the body typically free from germs; they <a href="https://www.cdc.gov/groupastrep/igas-infections-investigation.html">seem to be on the rise</a> after a marked <a href="https://www.cdc.gov/groupastrep/igas-infections-investigation.html">reduction in their occurrence during the COVID-19 pandemic</a>. </p>
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<figcaption><span class="caption">Like other illnesses that made a comeback after COVID-19 prevention measures were relaxed, strep cases have returned to pre-pandemic levels.</span></figcaption>
</figure>
<h2>To test or not to test</h2>
<p>Doctors or other clinicians can easily test for strep by using a swab to collect a bit of the fluid from the back of the throat. This sample can identify group A strep in about a minute. </p>
<p>While researchers have been studying group A strep <a href="https://www.ncbi.nlm.nih.gov/books/NBK333430/">for over 75 years</a> and there are thousands of research papers focused on infections caused by strep, there is still <a href="https://www.nice.org.uk/guidance/ng84/chapter/Summary-of-the-evidence">controversy</a> over whether it needs to be tested for and treated. </p>
<p>To decide whether to test for group A strep, clinicians use a set of criteria based on <a href="https://www.mdcalc.com/calc/104/centor-score-modified-mcisaac-strep-pharyngitis">five questions</a> that can help determine whether strep testing is needed. These are:</p>
<p>– How old is the patient? Strep throat is most common in children <a href="https://www.cdc.gov/groupastrep/diseases-public/strep-throat.html#">between ages 5 and 15</a> and least common in <a href="https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html#">adults over age 45</a>. </p>
<p>– Are the tonsils swollen or do they have a white or yellow coating? Both conditions often accompany strep. However, this question alone isn’t definitive, since viruses can also affect the tonsils.</p>
<p>– Are the <a href="https://www.verywellhealth.com/cervical-lymph-nodes-2252142">cervical lymph nodes</a> swollen or tender? Normally these bumps, which are in the front of the neck along the sides of the windpipe, cannot be seen or felt, but are often palpable when strep is present.</p>
<p>– Does the person have a fever? Lack of a fever makes strep less likely.</p>
<p>– Does the person have a cough? A cough is indicative of a viral cause and makes strep the less likely cause of the sore throat.</p>
<p>While none of these questions alone can provide a clear answer, taken together they can tell your clinician whether strep is more or less likely. </p>
<p>Using this scoring tool, an adult with a sore throat but without changes to the tonsils or lymph nodes, without a fever and with a cough has only a <a href="https://www.mdcalc.com/calc/104/centor-score-modified-mcisaac-strep-pharyngitis">1 in 40 chance, or 2.5%, of having strep throat</a>. For such patients, a strep test is not necessary. </p>
<p>On the other hand, when a first grader meets all five of these criteria, there is a 50% chance that strep is causing his or her sore throat. Based on recent research I have reviewed, by using these questions <a href="https://doi.org/10.7326/0003-4819-159-9-201311050-00003">adults can determine</a> when strep is the likely cause of a sore throat. </p>
<p>In the <a href="https://www.nice.org.uk/guidance/ng84">United Kingdom</a> and <a href="https://doi.org/10.1370/afm.741">other European countries</a>, doctors do not routinely test for strep. Antibiotic treatment can at times <a href="https://www.cdc.gov/antibiotic-use/community/pdfs/aaw/au_arent_always_the_answer_fs_508.pdf">cause allergic reactions, rash, diarrhea, stomach upset, yeast infections and other side effects</a>. Authorities in these countries feel any benefit of testing and treatment does not outweigh these risks.</p>
<h2>Treatments for strep</h2>
<p>Once group A strep is confirmed, doctors may prescribe an antibiotic treatment. </p>
<p>Penicillin or amoxicillin are the most commonly prescribed antibiotics for strep. These medicines will not reduce pain or tiredness but may help symptoms resolve earlier, typically by <a href="https://www.nice.org.uk/guidance/ng84/chapter/Summary-of-the-evidence">about a day</a>. Doctors may also suggest use of a pain reliever such as acetaminophen or ibuprofen to help relieve symptoms.</p>
<p>Antibiotic treatment does not seem to lower the likelihood of <a href="https://doi.org/10.1136/bmj.38503.706887.AE1">spread of the infection between children</a> – which is common in schools and dormitories – <a href="https://doi.org/10.1136/bmj.f6867">or adults</a>.</p>
<p>Health care practitioners recommend staying home until fever has subsided. They also recommend taking the full course of antibiotics, even if the symptoms have abated. </p>
<p>With sore throats causes by viruses – against which antibiotics are ineffective – few treatments exist aside from using pain relievers to help soothe immediate symptoms. For this reason and because <a href="https://www.cdc.gov/antibiotic-use/index.html">antibiotic overuse is a major problem in the U.S.</a>, it is best not to assume that your sore throat is caused by strep and to treat it accordingly.</p><img src="https://counter.theconversation.com/content/207286/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Shaughnessy does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Despite an abundance of research on strep, there is still a great deal of debate in the scientific community over whether and when people should get tested and treated for it.Allen Shaughnessy, Professor of Family Medicine, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2077852023-06-23T15:51:06Z2023-06-23T15:51:06ZThe melting Arctic is a crime scene. The microbes I study have long warned us of this catastrophe – but they are also driving it<p>The Arctic’s climate is warming at least four times faster than the global average, causing irrevocable changes to this vast <a href="https://news.sky.com/story/dramatic-changes-to-polar-ice-caps-revealed-on-new-map-of-arctic-and-antarctica-12898550">landscape</a> and precarious <a href="https://www.nwf.org/Educational-Resources/Wildlife-Guide/Wild-Places/Arctic#:%7E:text=The%20Arctic%20is%20a%20unique,in%20the%20summer%20to%20breed.">ecosystem</a> – from the anticipated <a href="https://earth.org/polar-bears-to-become-extinct-by-2100/">extinction of polar bears</a> to the <a href="https://www.scientificamerican.com/article/as-arctic-sea-ice-melts-killer-whales-are-moving-in/#:%7E:text=Killer%20whales%20often%20feed%20on,navigate%20through%20the%20icy%20waters.">appearance of killer whales</a> in ever-greater numbers. A new <a href="https://www.nature.com/articles/s41467-023-38511-8">study</a> suggests the Arctic Ocean could be ice-free in summer <a href="https://theconversation.com/arctic-ocean-could-be-ice-free-in-summer-by-2030s-say-scientists-this-would-have-global-damaging-and-dangerous-consequences-206974">as soon as the 2030s</a> – around a decade earlier than previously predicted.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Map of Arctic sea ice changes" src="https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=700&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=700&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=700&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=879&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=879&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532508/original/file-20230618-17-lemk5e.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=879&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A new Arctic sea ice map compares the 30-year average with recent ten-year averages.</span>
<span class="attribution"><a class="source" href="https://www.bas.ac.uk/media-post/new-map-of-polar-regions-updated-to-reflect-ice-loss-name-changes-and-new-data/">British Antarctic Survey</a></span>
</figcaption>
</figure>
<p>But to properly understand the pace and force of what’s to come, we should instead focus on organisms too small to be seen with the naked eye. These single-celled microbes are both the watchkeepers and arch-agitators of the Arctic’s demise.</p>
<p>Scientists like me who study them have become forensic pathologists, processing crime scenes in our Arctic field sites. We don the same white anti-contamination suits, photograph each sampling site, and bag our samples for DNA analysis. In some areas, red-coloured microbes even create an effect known as “blood snow”.</p>
<p>In this complex criminal investigation, however, the invisible witnesses are also responsible for the damage being done. Microbes testify to the vulnerability of their Arctic habitats to the changes that humans have caused. But they also create powerful climate feedback loops that are doing ever-more damage both to the Arctic, and the planet as a whole.</p>
<h2>Zipping headlong into icy oblivion</h2>
<p>My first visit to the Arctic was also nearly my last. As a PhD student in my early 20s in 2006, I had set out with colleagues to sample microbes growing on a glacier in the Norwegian archipelago of <a href="https://www.theguardian.com/environment/2023/may/13/svalbard-the-arctic-islands-where-we-can-see-the-future-of-global-heating">Svalbard</a> – the planet’s northernmost year-round settlement, about 760 miles from the North Pole.</p>
<p>Our treacherous commute took us high above the glacier, traversing an icy scree slope to approach its flank before crossing a river at the ice’s margin. It was a route we had navigated recently – yet this day I mis-stepped. Time slowed as I slid towards the stream swollen with ice melt, my axe bouncing uselessly off the glassy ice. I was zipping headlong into icy oblivion.</p>
<p>In that near-death calm, two things bothered me. The water would carry me deep into the glacier, so it would be decades before my remains were returned to my family. And the ear-worm of that field season meant I would die to the theme tune to Indiana Jones.</p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><strong><em>This article is part of Conversation Insights</em></strong>
<br><em>The Insights team generates <a href="https://theconversation.com/uk/topics/insights-series-71218">long-form journalism</a> derived from interdisciplinary research. The team is working with academics from different backgrounds who have been engaged in projects aimed at tackling societal and scientific challenges.</em></p>
<hr>
<p>Thankfully, the scree slowed my slide – I lived and learned, quickly, that dead scientists don’t get to write up their papers. And I’m still learning about the tiny organisms that populate every habitat there: from seawater in the Arctic Ocean to ice crystals buried deep in the <a href="https://en.wikipedia.org/wiki/Greenland_ice_sheet">Greenland ice sheet</a>.</p>
<p>These micro-managers of all manner of planetary processes are acutely sensitive to the temperatures of their habitats. The slightest change above freezing can transform an Arctic landscape from a frozen waste devoid of liquid water to one where microbes get busy reproducing in nutrient-rich water, transforming themselves in ways that <a href="https://www.nature.com/articles/ismej2010108">further amplify</a> the effects of climate warming.</p>
<p>The Svalbard region is now warming seven times faster than the global average. While much of the world continues its efforts to limit global warming to 1.5°C above pre-industrial levels, in the Arctic, that battle was lost long ago.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/0VOGGdeB8eI?wmode=transparent&start=17" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Joseph Cook’s film on the microbes that inhabit the Greenland ice sheet.</span></figcaption>
</figure>
<h2>Decades ahead of us all</h2>
<p>It’s 2011, and <a href="http://www.earth.s.chiba-u.ac.jp/english/education/education02/staff16.html">Nozomu Takeuchi</a> is visiting Svalbard from Japan. It has been a difficult year back home, following the earthquake, tsunami and Fukushima nuclear incident, but Nozomu – a glacier ecologist and professor at Chiba University – is unrelenting in his quest to measure the effects of climate change. </p>
<p>Just hours after he stepped off a plane in the August midnight sun at Longyearbyen airport, we are marching up the nearest glacier. Above us, snow-capped mountain sides loom out of the swirling mist.</p>
<p>Since the 1990s, Nozomu has been collecting samples and measurements from glaciers all over the world. When we reach our goal near the snowline, he opens his rucksack to reveal a bento box full of sampling kit – stainless steel scoops, test tubes, sample bags, all arranged for efficiency. As he scurries around with practised efficiency, I think of offering help but fear I would only slow him down.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Scientist takes a reading in snowy Arctic landscape" src="https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=424&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=424&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=424&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=533&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=533&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532612/original/file-20230619-27-w8e0xr.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=533&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Nozomu Takeuchi measuring the biological darkening of a Svalbard glacier in 2011.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>In truth, Nozomu is decades ahead of us all. Years ago, he made the link between the future of life and the death of ice, and these melting Svalbard glaciers are adding yet more points to his graphs.</p>
<p>Just as we apply oodles of factor 50 to protect ourselves from the Sun, so the billions of microbes sandwiched between the sky and surface of the glacier protect themselves by accumulating sunscreen-like pigments. And if enough of these pigments rest in one place under the Sun, this area of “biological darkening” absorbs the heat of the Sun much more effectively than reflective white snow and ice – so it melts faster.</p>
<p>Nozomu scoops up some of the so-called blood snow, heavily laden with algae. Under the microscope, their cells are indeed reminiscent of red blood cells. But rather than haemoglobin, these cells are laden with carotenoids – pigments also found in vegetables that <a href="https://academic.oup.com/femsec/article/94/3/fiy007/4810544?login=false">protect the algae from overheating</a>. Other patches of the glacier are verdant green, rich in algae that are busy photosynthesising light into chemical energy in this 24-hour daylight world.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Man in icy landscape holding scientific sample" src="https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532611/original/file-20230619-29-l44kho.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The author with a sample of ‘blood snow’, collected from a glacier surface.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Further down the glacier, the professor crushes some “dirty” ice into a bag. A different kind of algae lives here that, depending on your point-of-view, is either black, brown or purple (perhaps it depends on the tint of your sunglasses). The <a href="https://www.researchgate.net/figure/Chemical-structure-of-compound-3-purpurogallin-carboxylic-acid-6-O-b-d-glucopyranoside_fig2_51806131#:%7E:text=A%20gallotannin%20derivative%20(galloylglucopyranose%2C%20i.e.,et%20al.%2C%202012b)%20.">pigment</a> created is like the compounds that colour tea, and the algae keep it in layers like parasols above the photosynthetic factories within their cells – ensuring they have just enough sunlight to photosynthesise, but not enough to burn.</p>
<p>Open Google Earth and as you zoom in on the Arctic, you may spot the large dark stripe that scars the western margin of the <a href="https://en.wikipedia.org/wiki/Greenland_ice_sheet">Greenland ice sheet</a>. This is the “dark zone”, but it’s not caused by dark <a href="https://www.nature.com/articles/s41467-020-20627-w">dust</a> or soot. It’s alive, <a href="https://www.nature.com/articles/ismej2012107">laden with algae</a> – and it has been darkening, and growing, as Greenland warms.</p>
<p>Between 2000 and 2014, the <a href="https://www.frontiersin.org/articles/10.3389/feart.2016.00043/full">dark zone’s area grew by 14%</a>. At 279,075 km² in 2012, it was already more than twice the <a href="https://www.britannica.com/summary/England#:%7E:text=Area%3A%2050%2C301%20sq%20mi%20(130%2C278,even%20with%20the%20entire%20kingdom.).%20This%20had%20a%20powerful%20impact%20on%20the%20rate%20of%20ice%20melt%20--%20areas%20blooming%20with%20algae%20%5Bmelt%20nearly%202cm%20more%20each%20day%5D(https://www.pnas.org/doi/abs/10.1073/pnas.1918412117">size of England</a> than bare ice.</p>
<p>Next morning, I am woken by the smell of chemicals, having slept beneath a coffee table. Nozomu is busy processing his samples: bags of melting ice pinned to a clothesline by bulldog clips. They resemble bunting around the crowded room, but this is no time for celebration. The tint of each bag adds a measurement which quantifies the link between these algae, their pigments, and the death of their icy home.</p>
<h2>The case becomes urgent</h2>
<p>By the summer of 2014, glaciologists all over the world have started to listen to the warnings of pioneering ecologists such as Nozomu. The glaciers are dying even as life blossoms on their darkening surfaces. The case has become urgent.</p>
<p>I am in a helicopter, flying with colleagues to a camp in the dark zone on the Greenland ice sheet – the largest mass of glacial ice in the northern hemisphere. Covering 1.7 million km², its ice holds the equivalent of the water required to raise global sea levels by 7.7 metres.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A landscape of dark ice intertwined with blue rivers of meltwater." src="https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532620/original/file-20230619-23-shc4a3.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A highly darkened surface of the Greenland ice sheet, rich in algae and incised with rivers of meltwater.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>As we warm our climate, the rate of water flowing from this reservoir increases, with each degree Celsius added to global temperatures opening the drainage valve even wider. Feedback processes such as biological darkening have the potential to multiply the number of drainage valves that are open, hastening dramatically the rate at which sea levels rise.</p>
<p>To monitor this effect, every day <a href="https://www.gla.ac.uk/schools/ges/staff/karencameron/">Karen Cameron</a>, the leader of our camp this summer, walks to undisturbed patches of ice carrying a £100,000 backpack which contains a spectrometer to measure the darkness of the ice, capturing how it absorbs the solar energy that causes melting. The glaciologists are desperate for ground truth, and their models need data.</p>
<p>Up to this point, none of their predictions of how the Greenland ice sheet would respond to our warming climate have included biological darkening. Even if the effect were modest, it could still topple the ice sheet from a predictable, straightline response to climate warming.</p>
<p>All the time we are in Greenland, the only lifeforms we encounter are the flies that hatch from the fresh fruit and peppers in our food rations. These and the few types of glacier algae and several hundred kinds of bacteria that are biologically darkening the ice: a living scum scarring the surface of the ice sheet.</p>
<p>My work focuses on how these tiny organisms adapt to their icy habitat, but the implications of their behaviour are now of global concern. A <a href="https://screenworks.org.uk/archive/baftss-practice-research-award-2017/timeline">filmmaker</a> at the camp is weaving a thread between the ice melt in Greenland and its consequences for people living in coastal communities all over the world – from villages near my home on the <a href="https://www.theguardian.com/environment/2019/may/18/this-is-a-wake-up-call-the-villagers-who-could-be-britains-first-climate-refugees">west coast of Wales</a>, to huge metropolises like Manhattan, Amsterdam and Mumbai, and even entire low-lying island nations in the Pacific.</p>
<p>As smaller glaciers fade, and the larger ice sheets of Greenland and Antarctica start to respond with full force to our warming climate, it is these communities, capitals and countries that will bear the brunt of the flooding, inundation and erosion that comes with rising sea levels.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two scientists inspecting an ice corer device dripping with meltwater." src="https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532622/original/file-20230619-28-oh4l8z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The author (left) and Joseph Cook high on the Greenland ice sheet, meltwater dripping from their ice corer.</span>
<span class="attribution"><span class="source">Sara Penrhyn Jones</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Before heading home, our helicopter takes us on a detour, high over the ice sheet. We fly over the brown-black-purple algae to brighter, higher elevations where the palette shrinks to the blue and white of water and ice, then snow and sky. Greenland makes its own weather and, in these higher elevations, we expect the ice to be frozen all year round. When we land and begin to collect snow samples and a small ice core, however, we find we are digging into slush. The ice has started to melt up here, too. </p>
<p>We heave up our ice corer, and meltwater dribbles out from its bottom. In periods of extreme warming, much of the surface of the ice sheet can experience melting episodes, <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2015.00225/full">disturbing the slumbering microbes</a> stored within the otherwise permanently frozen surface. It’s a sobering moment for us all.</p>
<p>Flying back to camp, I watch the streams become rivers and lakes as we head back over the dark zone, where melt and microbes dominate the icescape. I contemplate how much water, once locked in the ice, will become free to flow into the sea and into millions of homes by the end of the century.</p>
<h2>Popping a pingo</h2>
<p>The frozen lands of eight nations encircle the Arctic. Their soils store vast quantities of carbon: a third of the planet’s entire quantity of soil carbon resides in this frozen ground.</p>
<p>The carbon is a legacy of soils formed in past climates and preserved for millennia. However, human-induced climate change is reheating this leftover carbon, providing a luxuriant food source for microbes resident within the <a href="https://earthobservatory.nasa.gov/biome/biotundra.php">tundra</a>, which then emit it as greenhouse gases.</p>
<p>This is known as the <a href="https://en.wikipedia.org/wiki/Permafrost_carbon_cycle#:%7E:text=Carbon%20emissions%20from%20permafrost%20thaw,which%20increases%20permafrost%20thaw%20depths.">permafrost carbon</a> feedback loop. When even modest quantities of this vast carbon store reach the atmosphere, warming accelerates – resulting in faster thawing of the tundra and the release of yet more greenhouse gases.</p>
<p>Furthermore, not all greenhouse gases are equal in their impact. While carbon dioxide is relatively abundant and stable for centuries in the atmosphere, methane is less abundant and shorter-lived, but remarkably powerful as a greenhouse gas – nearly 30 times more damaging to the climate than carbon dioxide, for the same volume.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Scientist crouched on ice taking water samples." src="https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=307&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=307&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=307&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=386&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=386&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532615/original/file-20230619-1823-ekek0j.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=386&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Andy Hodson sampling methane from a freshly ‘popped’ pingo.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>For more than three decades, <a href="https://www.unis.no/staff/andy-hodson/">Andy Hodson</a> has worked at the frontier where microbes, carbon and the Arctic landscape meet. In 2018, we join him on a brisk spring day in Svalbard. It’s -26°C but the snowmobile commute is thankfully brief – then we work quickly against the cold.</p>
<p>Hodson’s plan is to “pop” one of the many <a href="https://en.wikipedia.org/wiki/Pingo">pingos</a> that populate the floor of this wide open valley. Think of pingos as the acne of the Arctic: they form as permafrost compresses unfrozen wet sediments, erupting as small hills blistering the skin of the tundra.</p>
<p>The story of these microbes’ lives is complicated. They only live beyond the reach of oxygen – where oxygen is more prevalent, methane-consuming microbes thrive instead, quenching the belches of methane from below. Similarly, should mineral sources of iron or sulphide be nearby, then microbes that use them outcompete the methanogens.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A small fountain of water in an opening in the ice, amid a snowy landscape." src="https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532614/original/file-20230619-15-6i78fv.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A popped pingo discharging supercooled water rich in methane.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>It all adds up to one of the greatest uncertainties for our civilisation: the extent and composition of greenhouse gases escaping from Arctic lands. <a href="https://www.cam.ac.uk/research/news/emissions-from-melting-permafrost-could-cost-43-trillion#:%7E:text=Increased%20greenhouse%20gas%20emissions%20from,and%20the%20University%20of%20Colorado.">Estimates of the economic impacts</a> from this permafrost carbon feedback tally in the tens of trillions of dollars to the global economy. We know it is bad news, but exactly how bad depends on the microbes in their microscopic mosaic.</p>
<p>Hodson’s field work shows that, during the Arctic winter, this pingo is probably the only source of methane in the immediate area, its chimney enabling the gas to escape from the depths of the ice before methane-consuming microbes can catch it. Annually, tens of kilograms of methane and more than a ton of carbon dioxide will escape from this pingo alone - one of <a href="https://doi.org/10.1016/j.geomorph.2023.108694">more than 10,000</a> scattered across the Arctic, in addition to its other methane-producing hotspots.</p>
<h2>A near-perfect ecosystem</h2>
<p>Arctic lands are a patchwork of permafrost carbon feedbacks, and our future depends on the uncertain fate of the microbes within. </p>
<p>While the ice melt enhances the growth of microbes in the short term, if it continues to the point of erasing habitats then the microbes will be lost with them. We recognise this danger for polar bears and walruses, but not the invisible biodiversity of the Arctic. Small does not mean insignificant though.</p>
<p>To appreciate this, we can head back to the dark zone on Greenland’s ice sheet and join <a href="https://www.rolex.org/rolex-awards/exploration/joseph-cook">Joseph Cook</a> during our summer 2014 field season. He’s lying on a mat improvised from a bath towel and a binbag wrapped in duct tape, peering into a dark, pothole-like depression in the ice. It’s a cryoconite hole, and millions of them are dotted over the edges of the ice sheet. Where pingos contribute to climate warming by emitting methane, cryoconite is a good sink of greenhouse gases, but this creates its own problems. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Crouching scientist takes samples in the Arctic snow." src="https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532618/original/file-20230619-27-4a5amn.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Joseph Cook measuring the carbon cycling activities of Greenland’s cryoconite holes.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2486.2008.01758.x">earliest estimate</a> of its ability to store carbon dioxide from the air on the ice surface of the world’s glaciers exceeded Finland’s total carbon emissions in the same year. Every cryoconite hole is a near-perfect ecosystem – with a singular flaw. Its inhabitants must melt ice to live. But the very act of melting the ice hastens the demise of their glacier habitat. </p>
<p>Despite being found in some of the harshest locations on Earth, cryoconite is home for thousands of different types of bacteria (including the all-important photosynthetic cyanobacteria), fungi, and <a href="https://microbiologysociety.org/why-microbiology-matters/what-is-microbiology/protozoa.html">protozoa</a>. Even <a href="https://www.theguardian.com/environment/2020/oct/17/tardigrade-ice-hole-arctic-greenland">tardigrades</a> thrive in cryoconite.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscope image of a single cryoconite granule." src="https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532623/original/file-20230619-21-7v4otj.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Microscope image of a cryoconite granule, showing biological darkening and cyanobacteria growing through it.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Cook is professionally besotted with the perfection of this near-frozen “microscopic rainforest”. Its inhabitants are shielded and nourished at just the right depth and in the right shape for a busy ecosystem to be engineered by the interaction of sunlight with cyanobacteria, dust and ice to the benefit of all its inhabitants. The cyanobacteria use sunshine to capture carbon dioxide from the air and convert it into the slimy cement that builds each granule of cryoconite</p>
<p>However, with vast numbers of cryoconite holes dotted across the ice surface, “swarms” of these holes help <a href="https://www.frontiersin.org/articles/10.3389/feart.2015.00078/full">shape and darken the ice surface</a>. This in turn influences the melting rate, as the surface is sculpted under the sun of 24-hour daylight.</p>
<p>Writing in the scientific journal <a href="https://www.nature.com/articles/029039a0">Nature in 1883</a>, Swedish polar explorer Adolf Erik Nordenskjöld, who discovered cryoconite, thanked the organisms within cryoconite for melting away the ancient ice that once covered Norway and Sweden:</p>
<blockquote>
<p>In spite of their insignificance, [they] play a very important part in nature’s economy, from the fact that their dark colour far more readily absorbs the Sun’s heat than the bluish-white ice, and thereby they contribute to the destruction of the ice sheet, and prevent its extension. Undoubtedly we have, in no small degree, to thank these organisms for the melting away of the layer of ice which once covered the Scandinavian peninsula.</p>
</blockquote>
<h2>Taking DNA analysis to strange new places</h2>
<p>We return to Greenland in winter 2018 to explore cryoconite’s singular flaw. Cook and I are joined by Melanie Hay, then a PhD student in Arctic bioinformatics.</p>
<p>Hay and I are taking DNA analysis to strange new places to learn more about the evolution and biology of cryoconite. Powerful advances in genomics are changing our view of the microbial world, but large DNA-sequencing instruments fare best in sophisticated labs.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Scientist sitting outside her tent with backpack, looking out at icy landscape." src="https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=442&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=442&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=442&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=555&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=555&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532619/original/file-20230619-17-uv14gu.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=555&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Melanie Hay camping and sampling on the Greenland ice sheet.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Instead, we are using a stapler-sized nanopore sequencer hooked up to the USB port of a winterised laptop. Outside the tent, it is –20°C – but the DNA sequencer must run at body temperature. The only sustainable source of warmth is body heat, so I have snuggled up with the sequencer in my sleeping bag every night and in my clothes all day.</p>
<p>That evening, we are caught in a storm of hurricane force. Becoming disorientated while moving between tents would be lethal, so we crawl in a human chain through the whiteout to our sleeping tents. Hay reaches her tent but Cook’s is lost, so we squeeze into my one-person tent. Somehow I sleep soundly, while Cook is exposed to the full force of the night’s terror.</p>
<p>In the morning, we excavate Hay, whose snow-laden tent had collapsed in the night. The sequencing is complete, but storm damage to our generator means the camp is losing power, so she must work quickly. She identifies the cyanobacteria building the cryoconite – it’s a short list dominated by one species: <em>Phormidesmis priestleyi</em>.</p>
<p>This species, found in cryoconite throughout the Arctic, seems to be the ecosystem engineer of cryoconite – a microscopic beaver building a dam of dust. But the flaw is the darkness of the near-perfect cryoconite ecosystems it creates. Like the neighbouring glacier algae we met earlier, <em>Phormidesmis priestleyi</em> is biologically darkening Arctic ice, and eventually hastening the demise of the thousands of different types of organism contained in cryoconite holes.</p>
<p>And so, this work shows us ever more clearly that the <a href="https://www.nature.com/articles/s41559-020-1163-0">loss of the planet’s glaciers</a> is as much a component of the global biodiversity crisis as it is a headline impact of climate change.</p>
<h2>Last line of defence against antibiotic resistance</h2>
<p>The loss of the Arctic’s microbial biodiversity matters in other ways too. Hay and Aliyah Debbonaire are both reformed biomedical scientists seeking cures from the Arctic in the form of new antibiotics. In the summer of 2018, we are in Svalbard looking for clues.</p>
<p>The world is running out of effective antibiotics, and the Arctic’s frontiers may be our last line of defence in this antibiotic resistance crisis. Countless species of microbes have evolved to live within its harsh habitats using all the tricks in the book, including making antibiotics as chemical weapons to kill off competitors. This means they may be sources of new antibiotics.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Scientists (one kneeling) taking samples in the snowy Arctic landscape." src="https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=413&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=413&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=413&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=519&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=519&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532631/original/file-20230619-1900-kr9gwx.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=519&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Aliyah Debbonaire (left) and Melanie Hay sampling a cryoconite hole.</span>
<span class="attribution"><span class="source">Arwyn Edwards</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>And this is not their only application. From cheeses to eco-friendly biological washing powders, entire shopping aisles of products have been derived from cold-adapted microbes. As climate warming threatens to disrupt entire Arctic habitats, our opportunity to use, learn from, and protect this biodiversity may be lost forever.</p>
<p>As our tiny plane returns to the nearest town, Longyearbyen, we fly low over the <a href="https://theconversation.com/after-svalbard-why-safety-of-world-seed-vaults-is-crucial-to-future-food-security-79586">Svalbard Global Seed Vault</a>, which contains the fruits of more than 12,000 years of agriculture in the form of seeds from a million different varieties of crop. Nearby, a similar facility inside a disused coal mine stores essential computer programmes on microfilm – the ultimate backup for our data-addicted world.</p>
<p>Within a snowy kilometre, you can walk between the the alpha and omega of human innovation in civilisation. Both facilities have chosen the fastest-warming town on the planet as the safest place to store these treasures of humanity. Yet no such facility is dedicated to the microbial biodiversity of the Arctic, despite its critical importance to the future of the world’s biotech and medical sectors.</p>
<p>Instead, it falls to microbiologists such as Debbonaire, racing against time to identify, nurture and screen the microbes of the melting Arctic. Her painstaking work accumulates towers of Petri dishes, each a temporary refuge for a different Arctic microbe.</p>
<p>Eventually, they will be stored in <a href="https://www.dellamarca.it/en/how-does-an-ultra-low-freezer-work/">ultra-freezers</a> in laboratories scattered across the world. Such work is unglamorous to funders, so it is done piecemeal on the edges of other projects. Yet it represents our only attempt to save the microbes of the Arctic.</p>
<h2>The battle is lost</h2>
<p>Most of all, the Arctic matters because it is the fastest-warming part of the planet, and its microbes are responding first. What happens there carries implications for everyone. It is the harbinger of change for everywhere.</p>
<p>Another Arctic microbiologist could strike plangent notes regarding permafrost or sea ice, but as an ecologist of glaciers I am drawn to glacial ice.</p>
<p>Over the first fifth of this century, Earth’s glaciers have discharged some ten quadrillion (ten to the power 25) tablespoons of melt a year – and within each tablespoon, the <a href="https://www.nature.com/articles/s43247-022-00609-0">tens of thousands of bacteria and viruses</a> that were once stored within that ice.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/meltwater-is-infiltrating-greenlands-ice-sheet-through-millions-of-hairline-cracks-destabilizing-its-structure-207468">Meltwater is infiltrating Greenland’s ice sheet through millions of hairline cracks – destabilizing its structure</a>
</strong>
</em>
</p>
<hr>
<p>What’s to come is sadly predictable. Even the most modest warming scenario of 1.5°C above the pre-industrial era will lead to the extinction of at least <a href="https://www.science.org/doi/10.1126/science.abo1324">half the Earth’s 200,000 glaciers</a> by the end of the century.</p>
<p>Depending on the urgency and effectiveness of our actions as a civilisation, this century could also represent the “peak melt” in our history. Yet the battle to save many of these precious icy habitats is already lost. Instead, for scientists like me, our field work is now largely a question of documenting these “crime scenes” – so at least the knowledge of life within ice can be preserved, before it melts away forever.</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><em>For you: more from our <a href="https://theconversation.com/uk/topics/insights-series-71218?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Insights series</a>:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/prehistoric-communities-off-the-coast-of-britain-embraced-rising-seas-what-this-means-for-todays-island-nations-147879?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Prehistoric communities off the coast of Britain embraced rising seas – what this means for today’s island nations
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<li><p><em><a href="https://theconversation.com/climate-scientists-concept-of-net-zero-is-a-dangerous-trap-157368?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Climate scientists: concept of net zero is a dangerous trap
</a></em></p></li>
<li><p><em><a href="https://theconversation.com/noise-in-the-brain-enables-us-to-make-extraordinary-leaps-of-imagination-it-could-transform-the-power-of-computers-too-192367?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Noise in the brain enables us to make extraordinary leaps of imagination. It could transform the power of computers too
</a></em></p></li>
<li><p><em><a href="https://theconversation.com/beyond-gdp-changing-how-we-measure-progress-is-key-to-tackling-a-world-in-crisis-three-leading-experts-186488?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Beyond GDP: changing how we measure progress is key to tackling a world in crisis – three leading experts
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<p><em>To hear about new Insights articles, join the hundreds of thousands of people who value The Conversation’s evidence-based news. <a href="https://theconversation.com/uk/newsletters/the-daily-newsletter-2?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK"><strong>Subscribe to our newsletter</strong></a>.</em></p><img src="https://counter.theconversation.com/content/207785/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arwyn Edwards receives funding from UK Research & Innovation - Natural Environment Research Council, as well as the Research Council of Norway, the Leverhulme Trust, and the Royal Geographical Society. </span></em></p>To fully understand the extent of climate-related dangers the Arctic – and our planet – is facing, we must focus on organisms too small to be seen with the naked eye.Arwyn Edwards, Reader in Biology, Department of Life Sciences, Aberystwyth UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2069322023-06-04T11:19:08Z2023-06-04T11:19:08ZRemoving antimicrobial resistance from the WHO’s ‘pandemic treaty’ will leave humanity extremely vulnerable to future pandemics<figure><img src="https://images.theconversation.com/files/529846/original/file-20230602-27-nnu80l.png?ixlib=rb-1.1.0&rect=17%2C80%2C1680%2C1219&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antimicrobial resistance is now a leading cause of death worldwide due to drug-resistant infections, including drug-resistant strains of tuberculosis, pneumonia and Staph infections like the methicillin-resistant Staphylococcus aureus shown here.</span> <span class="attribution"><span class="source">(NIAID, cropped from original)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/removing-antimicrobial-resistance-from-the-who-s--pandemic-treaty--will-leave-humanity-extremely-vulnerable-to-future-pandemics" width="100%" height="400"></iframe>
<p>In late May, the latest version of the draft Pandemic Instrument, also referred to as the “pandemic treaty,” was shared with Member States at the <a href="https://www.who.int/about/governance/world-health-assembly">World Health Assembly</a>. The text was made available online via <a href="https://healthpolicy-watch.news/wp-content/uploads/2023/05/DRAFT_INB_Bureau-text_22-May.pdf">Health Policy Watch</a> and it quickly became apparent that all mentions of addressing antimicrobial resistance in the Pandemic Instrument were at risk of removal.</p>
<p>Work on the Pandemic Instrument began in December 2021 after the World Health Assembly agreed to a global process to draft and negotiate an international instrument — under the Constitution of the World Health Organization (WHO) — to protect nations and communities from future pandemic emergencies.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/drug-resistant-superbugs-a-global-threat-intensified-by-the-fight-against-coronavirus-135790">Drug-resistant superbugs: A global threat intensified by the fight against coronavirus</a>
</strong>
</em>
</p>
<hr>
<p>Since the beginning of negotiations on the Pandemic Instrument, there have been calls from civil society and leading experts, including the <a href="https://www.amrleaders.org/docs/librariesprovider20/default-document-library/amr-as-substantive-element-of-the-international-instument-of-pandemic-prevention-preparedness-and-response.pdf?sfvrsn=300292c8_5&download=true">Global Leaders Group on Antimicrobial Resistance</a>, to include the so-called “silent” pandemic of antimicrobial resistance in the instrument.</p>
<p>Just three years after the onset of a global pandemic, it is understandable why Member States negotiating the Pandemic Instrument have focused on preventing pandemics that resemble COVID-19. But not all pandemics in the past have been caused by viruses and not all pandemics in the future will be caused by viruses. Devastating past pandemics of bacterial diseases have included <a href="https://www.who.int/news-room/fact-sheets/detail/plague">plague</a> and <a href="https://www.who.int/news-room/fact-sheets/detail/cholera">cholera</a>. The next pandemic could be caused by bacteria or other microbes.</p>
<h2>Antimicrobial resistance</h2>
<figure class="align-right ">
<img alt="Yellow particles on purple spikes" src="https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Microscopic view of Yersinia pestis, the bacteria that cause bubonic plague, on a flea. Plague is an example of previous devastating pandemics of bacterial disease.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Antimicrobial resistance (AMR) is the process by which infections caused by microbes become resistant to the medicines developed to treat them. Microbes include bacteria, fungi, viruses and parasites. Bacterial infections alone cause <a href="https://www.tropicalmedicine.ox.ac.uk/gram/news/bacterial-infections-linked-to-one-in-eight-global-deaths-according-to-gram-study">one in eight deaths</a> globally.</p>
<p>AMR is fueling the rise of drug-resistant infections, including <a href="https://www.cdc.gov/tb/publications/factsheets/drtb/xdrtb.htm">drug-resistant tuberculosis</a>, <a href="https://www.cdc.gov/drugresistance/pdf/threats-report/strep-pneumoniae-508.pdf">drug-resistant pneumonia</a> and drug-resistant Staph infections such as <a href="https://www.cdc.gov/mrsa/index.html">methicillin-resistant Staphylococcus aureus</a> (MRSA). These infections are killing and debilitating millions of people annually, and <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">AMR is now a leading cause of death worldwide</a>. </p>
<p>Without knowing what the next pandemic will be, the “pandemic treaty” must plan, prepare and develop effective tools to respond to a wider range of pandemic threats, not solely viruses.</p>
<p>Even if the world faces another viral pandemic, <a href="https://theconversation.com/when-covid-19-or-flu-viruses-kill-they-often-have-an-accomplice-bacterial-infections-187056">secondary bacterial infections</a> will be a serious issue. During the COVID-19 pandemic for instance, large percentages of those hospitalized with COVID-19 required treatment for secondary bacterial infections. </p>
<p>New research from Northwestern University suggests that many of the deaths among hospitalized COVID-19 patients <a href="https://news.feinberg.northwestern.edu/2023/05/05/secondary-bacterial-pneumonia-drove-many-covid-19-deaths/">were associated with pneumonia — a secondary bacterial infection that must be treated with antibiotics</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An illustrative diagram that shows the difference between a drug resistant bacteria and a non-resistant bacteria." src="https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=558&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=558&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=558&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=701&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=701&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=701&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Antimicrobial resistance means infections that were once treatable are much more difficult to treat.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Treating these bacterial infections requires effective antibiotics, and with AMR increasing, <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">effective antibiotics are becoming a scarce resource</a>. Essentially, safeguarding the remaining effective antibiotics we have is critical to responding to any pandemic.</p>
<p>That’s why the potential removal of measures that would help mitigate AMR and better safeguard antimicrobial effectiveness is so concerning. Sections of the text which may be removed include measures to prevent infections (caused by bacteria, viruses and other microbes), such as:</p>
<ul>
<li> better access to safe water, sanitation and hygiene; </li>
<li> higher standards of infection prevention and control; </li>
<li> integrated surveillance of infectious disease threats from human, animals and the environment; and </li>
<li> strengthening <a href="https://www.cdc.gov/antibiotic-use/core-elements/index.html">antimicrobial stewardship</a> efforts to optimize how antimicrobial drugs are used and prevent the development of AMR.</li>
</ul>
<p>The exclusion of these measures would hinder efforts to protect people from future pandemics, and appears to be part of a <a href="https://www.nature.com/articles/d41586-023-01805-4">broader shift to water-down the language in the Pandemic Instrument</a>, making it easier for countries to opt-out of taking recommended actions to prevent future pandemics. </p>
<h2>Making the ‘pandemic treaty’ more robust</h2>
<p>Measures to address AMR could be easily included and addressed in the “pandemic treaty.”</p>
<p>In September 2022, I was part of a group of civil society and research organizations that specialize in mitigating AMR who were invited the WHO’s <a href="https://inb.who.int/">Intergovernmental Negotiating Body</a> (INB) to provide an <a href="https://amrpolicy.org/resources/recommendations-to-the-intergovernmental-negotiating-body-inb-concerning-amr-the-pandemic-instrument/">analysis on how AMR should be addressed</a>, within the then-draft text. </p>
<p>They outlined that including bacterial pathogens in the definition of “pandemics” was critical. They also identified specific provisions that should be tweaked to track and address both viral and bacterial threats. These included AMR and recommended harmonizing national AMR stewardship rules.</p>
<p>In March 2023, I joined other leading academic researchers and experts from various fields in publishing a special edition of the <a href="https://www.cambridge.org/core/journals/journal-of-law-medicine-and-ethics/issue/DC40B54126C7B273BD62EBEED9641D2A"><em>Journal of Medicine, Law and Ethics</em>,</a> outlining why the Pandemic Instrument must address AMR. </p>
<p>The researchers of this special issue argued that the Pandemic Instrument was overly focused on viral threats and ignored AMR and bacterial threats, including the need to manage antibiotics as a common-pool resource and revitalize research and development of novel antimicrobial drugs. </p>
<h2>Next steps</h2>
<p>While <a href="https://apps.who.int/gb/inb/pdf_files/inb4/A_INB4_3-en.pdf">earlier drafts of the Pandemic Instrument</a> drew on guidance from AMR policy researchers and civil society organizations, after the first round of closed-door negotiations by Member States, all of these insertions, are now at risk for removal.</p>
<p>The Pandemic Instrument is the best option to mitigate AMR and safeguard lifesaving antimicrobials to treat secondary infections in pandemics. AMR exceeds the capacity of any single country or sector to solve. Global political action is needed to ensure the international community works together to collectively mitigate AMR and support the conservation, development and equitable distribution of safe and effective antimicrobials.</p>
<p>By missing this opportunity to address AMR and safeguard antimicrobials in the Pandemic Instrument, we severely undermine the broader goals of the instrument: to protect nations and communities from future pandemic emergencies.</p>
<p>It is important going forward that Member States recognize the core infrastructural role that antimicrobials play in pandemic response and strengthen, rather than weaken, measures meant to safeguard antimicrobials. </p>
<p>Antimicrobials are an essential resource for responding to pandemic emergencies that must be protected. If governments are serious about pandemic preparedness, they must support bold measures to conserve the effectiveness of antimicrobials within the Pandemic Instrument.</p><img src="https://counter.theconversation.com/content/206932/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Susan Rogers Van Katwyk is a member of the WHO Collaborating Centre on Global Governance of Antimicrobial Resistance at York University. She receives funding from the Wellcome Trust and the Social Sciences and Humanities Research Council of Canada. </span></em></p>Drug-resistant microbes are a serious threat for future pandemics, but the new draft of the WHO’s international pandemic agreement may not include provisions for antimicrobial resistance.Susan Rogers Van Katwyk, Adjunct Professor, School of Global Health and Managing Director, AMR Policy Accelerator, York University, CanadaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2020842023-05-08T12:18:30Z2023-05-08T12:18:30ZGain-of-function research is more than just tweaking risky viruses – it’s a routine and essential tool in all biology research<figure><img src="https://images.theconversation.com/files/523909/original/file-20230502-4095-u8oni1.jpg?ixlib=rb-1.1.0&rect=0%2C94%2C1500%2C1221&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gain-of-function experiments in the lab can help researchers get ahead of viruses naturally gaining the ability to infect people in the wild.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/molecule-illustration-royalty-free-illustration/1423893041">KTSDesign/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The term “gain of function” is often taken to refer to research with viruses that puts society at risk of an infectious disease outbreak for questionable gain. Some research on emerging viruses can result in variants that gain the ability to infect people but this does not necessarily mean the research is dangerous or that it is not fruitful. Concerns have focused on lab research on the <a href="https://www.theguardian.com/world/2012/mar/28/bird-flu-mutant-strains">virus that causes bird flu</a> in 2012 and on the <a href="https://theconversation.com/why-gain-of-function-research-matters-162493">virus that causes COVID-19</a> since 2020. The National Institutes of Health had previously implemented a <a href="https://www.science.org/content/article/nih-lifts-3-year-ban-funding-risky-virus-studies">three-year moratorium</a> on gain-of-function research on certain viruses, and some U.S. legislatures have <a href="https://www.washingtonexaminer.com/news/senate/texas-state-ban-gain-function-research-covid-pandemic">proposed bills prohibiting</a> gain-of-function research on “potentially pandemic pathogens.”</p>
<p>The possibility that a genetically modified virus could escape the lab needs to be taken seriously. But it does not mean that gain-of-function experiments are inherently risky or the purview of mad scientists. In fact, gain-of-function approaches are a fundamental tool in biology used to study much more than just viruses, contributing to many, if not most, modern discoveries in the field, including <a href="https://doi.org/10.3201%2Feid2305.161556">penicillin</a>, <a href="https://theconversation.com/anti-cancer-car-t-therapy-reengineers-t-cells-to-kill-tumors-and-researchers-are-expanding-the-limited-types-of-cancer-it-can-target-196471">cancer immunotherapies</a> and <a href="https://www.sciencedaily.com/releases/2015/02/150204134119.htm">drought-resistant crops</a>.</p>
<p>As <a href="https://scholar.google.com/citations?user=IXDoiY4AAAAJ&hl=en">scientists who</a> <a href="https://scholar.google.com/citations?user=GBQiazwAAAAJ&hl=en">study viruses</a>, we believe that misunderstanding the term “gain of function” as something nefarious comes at the cost of progress in human health, ecological sustainability and technological advancement. Clarifying what gain-of-function research really is can help clarify why it is an essential scientific tool.</p>
<h2>What is gain of function?</h2>
<p>To study how a living thing operates, scientists can change a specific part of it and then observe the effects. These changes sometimes result in the organism’s gaining a function it didn’t have before or losing a function it once had. </p>
<p>For example, if the goal is to enhance the tumor-killing ability of immune cells, researchers can take a sample of a person’s immune cells and modify them to express a protein that specifically targets cancer cells. This mutated immune cell, called a <a href="https://theconversation.com/anti-cancer-car-t-therapy-reengineers-t-cells-to-kill-tumors-and-researchers-are-expanding-the-limited-types-of-cancer-it-can-target-196471">CAR-T cell</a> thereby “gains the function” of being able to bind to cancerous cells and kill them. The advance of similar immunotherapies that help the immune system attack cancer cells is based on the exploratory research of scientists who synthesized such “<a href="https://doi.org/10.1007/BF00820662">Frankenstein” proteins</a> in the 1980s. At that time, there was no way to know how useful these chimeric proteins would be to cancer treatment today, some 40 years later. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/mXADrg_ckhI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">CAR-T cell therapy involves giving a patient’s immune cells an increased ability to target cancer cells.</span></figcaption>
</figure>
<p>Similarly, by adding specific genes into rice, corn or wheat plants that increase their production in diverse climates, scientists have been able to produce plants that are able to grow and thrive in geographical regions they previously could not. This is a critical advance to maintain food supplies in the face of climate change. Well-known examples of food sources that have their origins in gain-of-function research <a href="https://www.sciencenews.org/article/rice-agriculture-feeds-world-climate-change-drought-flood-risk">include rice plants</a> that can grow in high flood plains or in drought conditions or that contain vitamin A to reduce malnutrition.</p>
<h2>Medical advances from gain-of-function research</h2>
<p>Gain-of-function experiments are ingrained in the scientific process. In many instances, the benefits that stem from gain-of-function experiments are not immediately clear. Only decades later does the research bring a new treatment to the clinic or a new technology within reach. </p>
<p>The development of most antibiotics have relied on the <a href="https://doi.org/10.3389/fcimb.2021.684515">manipulation of bacteria or mold</a> in gain-of-function experiments. Alexander Fleming’s initial discovery that the mold <em>Penicillium rubens</em> could produce a compound toxic to bacteria was a profound medical advance. But it wasn’t until scientists experimented with <a href="https://www.sciencemuseum.org.uk/objects-and-stories/how-was-penicillin-developed">growth conditions and mold strains</a> that therapeutic use of penicillin became feasible. Using a specific growth medium allowed the mold to gain the function of increased penicillin production, which was essential for its mass production and widespread use as a drug. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Worker monitoring penicillin capsules coming down production line" src="https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=759&fit=crop&dpr=1 600w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=759&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=759&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=954&fit=crop&dpr=1 754w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=954&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/523678/original/file-20230501-1518-hmu9o0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=954&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Gain-of-function research played a key role in the development and mass production of penicillin.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/penicillin-capsules-being-checked-as-they-come-off-the-news-photo/2667016">Wesley/Stringer/Hulton Archive via Getty Images</a></span>
</figcaption>
</figure>
<p>Research on <a href="https://doi.org/10.1128%2FAAC.02381-18">antibiotic resistance</a> also relies heavily on gain-of-function approaches. Studying how bacteria <a href="https://theconversation.com/looming-behind-antibiotic-resistance-is-another-bacterial-threat-antibiotic-tolerance-200226">gain resistance</a> against drugs is essential to developing new treatments microbes are unable to evade quickly.</p>
<p>Gain-of-function research in virology has also been critical to the advancement of science and health. <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2018/oncolytic-viruses-to-treat-cancer">Oncolytic viruses</a> are genetically modified in the laboratory to infect and kill cancerous cells like melanoma. Similarly, the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/overview-COVID-19-vaccines.html">Johnson & Johnson COVID-19 vaccine</a> contains an adenovirus altered to produce the spike protein that helps the COVID-19 virus infect cells. Scientists developed <a href="https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1654(199910/12)9:4%3C237::AID-RMV252%3E3.0.CO;2-G">live attenuated flu vaccines</a> by adapting them to grow at low temperatures and thereby lose the ability to grow at human lung temperatures. </p>
<p>By giving viruses new functions, scientists were able to develop new tools to treat and prevent disease.</p>
<h2>Nature’s gain-of-function experiments</h2>
<p>Gain-of-function approaches are needed to advance understanding of viruses in part because these processes already occur in nature.</p>
<p>Many viruses that infect such nonhuman animals as bats, pigs, birds and mice have the potential to <a href="https://theconversation.com/what-is-spillover-bird-flu-outbreak-underscores-need-for-early-detection-to-prevent-the-next-big-pandemic-200494">spill over into people</a>. Every time a virus copies its genome, it makes mistakes. Most of these mutations are detrimental – they reduce a virus’s ability to replicate – but some may allow a virus to replicate faster or better in human cells. Variant viruses with these rare, beneficial mutations will spread better than other variants and therefore come to dominate the viral population – that is <a href="https://www.amnh.org/exhibitions/darwin/evolution-today/natural-selection-vista">how natural selection works</a>.</p>
<p>If these viruses can replicate even a little bit within people, they have the potential to adapt and thereby thrive in their new human hosts. That is nature’s gain-of-function experiment, and <a href="https://doi.org/10.1093/ve/veaa016">it is</a> <a href="https://doi.org/10.1016/j.chom.2020.08.011">happening constantly</a>.</p>
<p>Gain-of-function experiments in the lab can help scientists <a href="https://doi.org/10.1126%2Fscience.1222526">anticipate the changes</a> viruses may undergo in nature by understanding what specific features allow them to transmit between people and infect them. In contrast to nature’s experiments, these are conducted in <a href="https://www.cdc.gov/labs/BMBL.html">highly controlled lab conditions</a> designed to limit infection risk to laboratory personnel and others, including air flow control, personal protective equipment and waste sterilization.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="People in protective clothing collecting dead pelicans on a beach" src="https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/523674/original/file-20230501-20-lxf4la.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Researchers and public health officials are concerned that the bird flu virus is evolving to more readily infect people.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/BirdFluMutations/6895d38a33de468c93c14da427b4dfff">Guadalupe Pardo/AP Photo</a></span>
</figcaption>
</figure>
<p>It is important that researchers carefully observe lab safety to minimize the theoretical risk of infecting the general population. It is equally important that virologists continue to apply the tools of modern science to gauge the risk of natural viral spillovers before they become outbreaks. </p>
<p>A <a href="https://theconversation.com/as-bird-flu-continues-to-spread-in-the-us-and-worldwide-whats-the-risk-that-it-could-start-a-human-pandemic-4-questions-answered-200204">bird flu outbreak</a> is currently raging across multiple continents. While the H5N1 virus is primarily infecting birds, some people have gotten sick too. More spillover events can change the virus in ways that would allow it to <a href="https://doi.org/10.1126/science.adi1013">transmit more efficiently among people</a>, potentially leading to a pandemic. </p>
<p>Scientists have a better appreciation of the tangible risk of bird flu spillover because of <a href="https://doi.org/10.1126/science.1213362">gain-of-function experiments</a> <a href="https://doi.org/10.1038/nature10831">published a decade ago</a>. Those lab studies showed that bird flu viruses could be transmitted through the air between ferrets within a few feet of one another. They also revealed multiple features of the evolutionary path the H5N1 virus would need to take before it becomes transmissible in mammals, informing what signatures researchers need to look out for during surveillance of the current outbreak.</p>
<h2>Oversight on gain of function</h2>
<p>Perhaps this sounds like a semantic argument, and in many respects it is. <a href="https://www.statnews.com/2021/12/23/gain-of-function-research-advances-knowledge-and-saves-lives/">Many researchers</a> would likely agree that gain of function as a general tool is an important way to study biology that should not be restricted, while also arguing that it should be curtailed for research on specific dangerous pathogens. The problem with this argument is that pathogen research needs to include gain-of-function approaches in order to be effective – just as in any area of biology.</p>
<p><a href="https://doi.org/10.1128/jvi.00089-23">Oversight of gain-of-function research</a> on potential pandemic pathogens already exists. Multiple layers of safety measures at the institutional and national levels minimize the risks of virus research.</p>
<p>While updates to current oversight are not unreasonable, we believe that <a href="https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-report-national-science-advisory-board-biosecurity">blanket bans or additional restrictions</a> on gain-of-function research do not make society safer. They may instead slow research in areas ranging from cancer therapies to agriculture. Clarifying which specific research areas are of concern regarding gain-of-function approaches can help identify how the current oversight framework can be improved.</p><img src="https://counter.theconversation.com/content/202084/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Seema Lakdawala receives funding from National Institutes of Health and the Flu Lab. </span></em></p><p class="fine-print"><em><span>Anice Lowen receives research funding from the National Institutes of Health and Flu Lab. </span></em></p>From cancer immunotherapy and antibiotics to GMO crops and pandemic surveillance, gain of function is a cornerstone of basic research.Seema Lakdawala, Associate Professor of Microbiology and Immunology at Emory University and Adjunct Professor Microbiology and Molecular Genetics, University of PittsburghAnice Lowen, Associate Professor of Microbiology and Immunology, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2048882023-05-04T19:06:29Z2023-05-04T19:06:29ZReconstructing ancient bacterial genomes can revive previously unknown molecules – offering a potential source for new antibiotics<figure><img src="https://images.theconversation.com/files/523906/original/file-20230502-2182-swsnio.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8256%2C5499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ancient DNA preserved in the tooth tartar of human fossils encodes microbial metabolites that could be the next antibiotic.</span> <span class="attribution"><a class="source" href="https://www.eurekalert.org/multimedia/983784?">Werner/Siemens Foundation</a></span></figcaption></figure><p>Microorganisms – in particular bacteria – are skillful chemists that can produce an impressive diversity of chemical compounds known as <a href="https://theconversation.com/nature-is-the-worlds-original-pharmacy-returning-to-medicines-roots-could-help-fill-drug-discovery-gaps-176963">natural products</a>. These metabolites provide the microbes major evolutionary advantages, such as allowing them to interact with one another or their environment and helping defend against different threats. Because of the diverse functions bacterial natural products have, many have been <a href="https://doi.org/10.1021/acs.jnatprod.5b01055">used as medical treatments</a> such as antibiotics and anti-cancer drugs.</p>
<p>The microbial species alive today represent only a tiny fraction of the vast diversity of microbes that have inhabited Earth over the past <a href="https://theconversation.com/were-viruses-around-on-earth-before-living-cells-emerged-a-microbiologist-explains-197880">3 billion years</a>. Exploring this microbial past presents exciting opportunities to recover some of their lost chemistry. </p>
<p>Directly studying these metabolites in archaeological samples is virtually impossible because of their <a href="https://doi.org/10.1007/s11306-017-1270-3">poor preservation</a> over time. However, reconstructing them using the genetic blueprints of long-dead microbes could provide a path forward. </p>
<p>We are a team of <a href="https://scholar.google.com/citations?user=cDFcc3cAAAAJ&hl=en">anthropologists</a>, <a href="https://scholar.google.de/citations?user=trnMQ7MAAAAJ&hl=en">archaeogeneticists</a> and <a href="https://scholar.google.com/citations?user=26MgwRgAAAAJ&hl=en">biochemists</a> who study ancient microbes. By <a href="https://www.science.org/doi/10.1126/science.adf5300">generating previously unknown chemical compounds</a> from the reconstructed genomes of ancient bacteria, our newly published research provides a proof of concept for the potential use of fossil microbes as a source of new drugs.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Researcher weighing tooth fossil on a scale" src="https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=565&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=565&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=565&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=710&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=710&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524480/original/file-20230504-17-ivzxrf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=710&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A single ancient tooth preserves the genomes of millions of ancient bacteria.</span>
<span class="attribution"><span class="source">Felix Wey/Werner Siemens Foundation</span></span>
</figcaption>
</figure>
<h2>Reconstructing ancient genomes</h2>
<p>The cellular machinery producing bacterial natural products is encoded in genes that are typically in close proximity to one another, forming what are called <a href="https://doi.org/10.1016/j.tim.2016.07.006">biosynthetic gene clusters</a>. Such genes are difficult to detect and reconstruct from ancient DNA because very old genetic material breaks down over time, fragmenting into thousands or even millions of pieces. The end result is numerous tiny DNA fragments <a href="https://doi.org/10.1038/s43586-020-00011-0">less than 50 nucleotides long</a> all mixed together like a jumbled jigsaw puzzle.</p>
<p>We sequenced billions of such ancient DNA fragments, then improved a bioinformatic process called <a href="https://doi.org/10.1007/s40484-019-0166-9">de novo assembly</a> to digitally order the ancient DNA fragments in stretches of up to 100,000 nucleotides long – a 2,000-fold improvement. This process allowed us to identify not only what genes were present, but also their order in the genome and the ways they differ from bacterial genes known today – key information to uncovering their evolutionary history and function. </p>
<p>This method allowed us to take an unprecedented look at the genomes of microbes living up to 100,000 years ago, including species not known to exist today. Our findings push back the <a href="https://doi.org/10.1038/s41586-021-03532-0">previously oldest</a> <a href="https://doi.org/10.1186/s40168-021-01132-8">reconstructed microbial genomes</a> by more than 90,000 years.</p>
<p>In the microbial genomes we reconstructed from DNA extracted from ancient tooth tartar, we found a gene cluster that was shared by a high proportion of Neanderthals and anatomically modern humans living during the <a href="https://www.britannica.com/event/Stone-Age/Middle-Paleolithic">Middle and Upper Paleolithic</a> that lasted from 300,000 to 12,000 years ago. This cluster bore the <a href="https://doi.org/10.1038/s43586-020-00011-0">molecular hallmarks of very ancient DNA</a> and belonged to the bacterial genus <em>Chlorobium</em>, a group of green sulfur bacteria capable of photosynthesis.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Chemical structure of paleofurans produced using ancient microbial DNA." src="https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=280&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=280&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=280&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=351&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=351&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524154/original/file-20230503-26-5xqprb.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=351&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">These paleofurans were produced from ancient microbial DNA.</span>
<span class="attribution"><span class="source">Pierre Stallforth</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We inserted a synthetic version of this gene cluster into a “modern” bacterium called <em>Pseudomona protegens</em> so it could produce the chemical compounds encoded in the ancient genes. Using this method, we were able to isolate two previously unknown compounds we named <a href="https://www.science.org/doi/10.1126/science.adf5300">paleofuran A and B</a> and determine their chemical structure. Resynthesizing these molecules in the lab from scratch confirmed their structure and allowed us to produce larger quantities for further analysis.</p>
<p>By reconstructing these ancient compounds, our findings highlight how archaeological samples could serve as new sources of natural products. </p>
<h2>Mining ancient natural products</h2>
<p>Microbes are constantly evolving and adapting to their surrounding environment. Because the environments they inhabit today differ from those of their ancestors, microbes today likely produce different natural products than ancient microbes from tens of thousands of years ago.</p>
<p>As recently as <a href="https://www.doi.org/10.1007/978-1-4613-1145-4_1">25,000 to 10,000 years ago</a>, the Earth underwent a major climate shift as it transitioned from the colder and more volatile <a href="https://www.britannica.com/science/Pleistocene-Epoch">Pleistocene Epoch</a> to the warmer and more temperate <a href="https://www.britannica.com/science/Holocene-Epoch">Holocene Epoch</a>. Human lifestyles also dramatically changed over this transition as people began living outside of caves and increasingly experimented with food production. These changes brought them into contact with different microbes through agriculture, animal husbandry and their new built environments. Studying Pleistocene-era bacteria may yield insights into bacterial species and biosynthetic genes no longer associated with humans today, and perhaps even microbes that have gone extinct.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/JfX06NINZpk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Changes in human lifestyles changed our genomes.</span></figcaption>
</figure>
<p>While the amount of data collected by scientists on biological organisms has exponentially increased over the past few decades, the <a href="https://theconversation.com/antibiotic-resistance-is-at-a-crisis-point-government-support-for-academia-and-big-pharma-to-find-new-drugs-could-help-defeat-superbugs-169443">number of new antibiotics has stagnated</a>. This is particularly problematic when bacteria are able to evade existing antibiotic treatments faster than researchers can develop new ones. </p>
<p>By reconstructing microbial genomes from archaeological samples, scientists can tap into the hidden diversity of natural products that would have otherwise been lost over time, increasing the number of potential sources from which they can discover new drugs.</p>
<h2>Scaling up ancient molecules</h2>
<p>Our study has shown that it is possible to access natural products from the past. To tap into the vast diversity of chemical compounds encoded in ancient DNA, we now need to streamline our methodology to be less labor-intensive. </p>
<p>We are currently optimizing and automating our process to identify biosynthetic genes in ancient DNA more quickly and reliably. We are also implementing robotic liquid handling systems to complete the time-consuming pipetting and bacterial cultivation steps in our methods. Our goal is to scale up the process to be able to translate a vast amount of data on ancient microbes into the discovery of new therapeutic agents. </p>
<p>Although we can recreate ancient molecules, their biological and ecological roles are difficult to decipher. Since the bacteria that originally produced these compounds no longer exist, we cannot culture or genetically manipulate them. Further study will need to rely on similar bacteria that can be found today. Whether or not the functions of these compounds have remained the same in the modern relatives of ancient microbes remains to be tested. Although the original functions of these compounds for ancient microbes may be unknown, they still have the potential to be repurposed to treat modern diseases.</p>
<p>Ultimately, we aim to shed new light on microbial evolution and fight the current antibiotic crisis by providing a new time axis for antibiotic discovery.</p><img src="https://counter.theconversation.com/content/204888/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christina Warinner receives funding from the Werner Siemens Foundation, the Francis Goelet Charitable Trust, the European Research Council, the United States National Science Foundation, and the Deutsche Forschungsgemeinschaft. She is affiliated with the Max Planck Institute for Evolutionary Anthropology, the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI), and the Biological Faculty of Friedrich Schiller University Jena. </span></em></p><p class="fine-print"><em><span>Alexander Hübner receives funding from the Werner Siemens Foundation, the European Research Council, and the Deutsche Forschungsgemeinschaft. He is affiliated with with the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI).</span></em></p><p class="fine-print"><em><span>Pierre Stallforth receives funding from the Werner Siemens Foundation, the Deutsche Forschungsgemeinschaft, and the Leibniz Association. He is affiliated with with the Leibniz Institute of Natural Product Research and Infection Biology (Leibniz-HKI) and the Friedrich Schiller University, Jena, Germany.</span></em></p>Ancient microbes likely produced natural products their descendants today do not. Tapping into this lost chemical diversity could offer a potential source of new drugs.Christina Warinner, Associate Professor of Anthropology, Harvard UniversityAlexander Hübner, Postdoctoral Researcher in Archaeogenetics, Max Planck Institute for Evolutionary AnthropologyPierre Stallforth, Professor of Bioorganic Chemistry and Paleobiotechnology, Friedrich-Schiller-Universität JenaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2002262023-04-11T12:04:46Z2023-04-11T12:04:46ZLooming behind antibiotic resistance is another bacterial threat – antibiotic tolerance<figure><img src="https://images.theconversation.com/files/519955/original/file-20230407-28-ddggzn.jpg?ixlib=rb-1.1.0&rect=0%2C3%2C2309%2C1292&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tolerant bacteria are dormant until an antibiotic threat has passed, then reemerge to conduct business as usual.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pseudomonas-aeruginosa-bacterium-illustration-royalty-free-image/1201441647">Christoph Burgstedt/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Have you ever had a nasty infection that just won’t seem to go away? Or a runny nose that keeps coming back? You may have been dealing with a bacterium that is tolerant of, though not yet resistant to, antibiotics. </p>
<p>Antibiotic resistance is a huge problem, contributing to <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">nearly 1.27 million deaths worldwide in 2019</a>. But antibiotic tolerance is a covert threat that researchers have only recently begun to explore. </p>
<p><a href="https://doi.org/10.1371/journal.ppat.1008892">Antibiotic tolerance</a> happens when a bacterium manages to survive for a long time after being exposed to an antibiotic. While <a href="https://doi.org/10.1128/microbiolspec.VMBF-0016-2015">antibiotic-resistant</a> bacteria flourish even in the presence of an antibiotic, tolerant bacteria often exist in a dormant state, neither growing nor dying but putting up with the antibiotic until they can “reawaken” once the stress is gone. Tolerance has been <a href="https://www.doi.org/10.1126/science.aaj2191">linked to the spread of antibiotic resistance</a>.</p>
<p>I am a <a href="https://doerr.wicmb.cornell.edu/current-lab-members/">microbiologist</a> who studies antibiotic tolerance, and I seek to uncover what triggers tolerant bacteria to enter a protective dormant slumber. By understanding why bacteria have the ability to become tolerant, researchers hope to develop ways to avoid the spread of this ability. The exact mechanism that sets tolerance apart from resistance has been unclear. But one possible answer may reside in a process that has been overlooked for decades: how bacteria <a href="https://doi.org/10.3389/fmicb.2020.577564">create their energy</a>.</p>
<h2>Cholera and antibiotic tolerance</h2>
<p>Many antibiotics are designed to <a href="https://doi.org/10.1039/C6MD00585C">break through the bacteria’s outer defenses</a> like a cannonball through a stone fortress. Resistant bacteria are immune to the cannonball because they can either destroy it before it damages their outer wall or change their own walls to be able to withstand the impact. </p>
<p>Tolerant bacteria can remove their wall entirely and avoid damage altogether. No wall, no target for the cannonball to smash. If the threat goes away before too long, the bacterium can rebuild its wall to protect it from other environmental dangers and resume normal functions. However, it is still unknown how bacteria know the antibiotic threat is gone, and what exactly triggers their reawakening. </p>
<p>My colleagues and I at the <a href="https://doerr.wicmb.cornell.edu/">Dörr Lab at Cornell University</a> are trying to understand processes of activation and reawakening in the tolerant bacteria responsible for cholera, <em>Vibrio cholerae</em>. <em>Vibrio</em> is <a href="https://doi.org/10.3389/fitd.2021.691604">rapidly evolving resistance</a> against various types of antibiotics, and doctors are concerned. As of 2010, <em>Vibrio</em> is already <a href="https://doi.org/10.1016/j.vaccine.2019.06.031">resistant to 36 different antibiotics</a>, and this number is expected to continue rising.</p>
<p>To study how <em>Vibrio</em> develops resistance, we chose a strain that is tolerant to a class of antibiotics <a href="https://doi.org/10.3389/fpubh.2016.00231">called beta-lactams</a>. Beta-lactams are the cannonball sent to destroy the bacteria’s fortress, and <em>Vibrio</em> adapts by activating two genes that temporarily remove its cell wall. I witnessed this phenomenon using a microscope. After removing its cell wall, the bacteria activate even more genes that morph it into fragile globs that can survive the effects of the antibiotic. Once the antibiotic is removed or degraded, <em>Vibrio</em> returns to its normal rod shape and continues to grow. </p>
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<figcaption><span class="caption">Normally rod-shaped <em>Vibrio cholerae</em> remove their cell walls and turn into globs in the presence of penicillin, enabling them to survive longer.</span></figcaption>
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<figcaption><span class="caption"><em>Vibrio cholerae</em> revert back to their rod-shaped structure once the antibiotic threat is removed.</span></figcaption>
</figure>
<p>In people, this process of tolerance is seen when a doctor prescribes an antibiotic, typically doxycycline, to a patient infected with cholera. The antibiotic temporarily seems to stop the infection. But then the symptoms start back up again because the antibiotics never fully cleared the bacteria in the first place.</p>
<p>The ability to revert back to normal and grow after the antibiotic is gone is the key to tolerant survival. Exposing <em>Vibrio</em> to an antibiotic for a long enough time would eventually kill it. But a standard course of antibiotics often isn’t long enough to get rid of all the bacteria even in their fragile state.</p>
<p>However, taking a medicine for a prolonged period can harm healthy bacteria and cells, causing further discomfort and illness. Additionally, <a href="https://doi.org/10.3389/fcimb.2020.572912">misuse and extended exposure</a> to antibiotics can increase the chances of other bacteria residing in the body becoming resistant.</p>
<h2>Other bacteria developing tolerance</h2>
<p><em>Vibrio</em> isn’t the only species to exhibit tolerance. In fact, researchers have recently identified many infectious bacteria that have developed tolerance. A bacteria family called <a href="https://doi.org/10.1371/journal.pbio.1001928">Enterobacteriaceae</a>, which include major food-borne disease pathogens <a href="https://doi.org/10.1371/journal.pbio.1001928"><em>Salmonella</em></a>, <a href="https://doi.org/10.1128/AAC.01282-08"><em>Shigella</em></a> and <a href="https://doi.org/10.1038/s41598-021-85509-7"><em>E. coli</em></a>, are just a few of the many types of bacteria that are capable of antibiotic tolerance.</p>
<p>As every bacterium is unique, the way one develops tolerance seems to be as well. Some bacteria, like <em>Vibrio</em>, <a href="https://doi.org/10.1128/AAC.00756-19">erase their cell walls</a>. Others can <a href="https://doi.org/10.1038/nchembio.1754">alter their energy sources, increase their ability to move or simply pump out</a> the antibiotic.</p>
<p>I recently found that a <a href="https://doi.org/10.1128/jb.00476-22">bacterium’s metabolism</a>, or the way it breaks down “food” to make energy, may play a significant role in its ability to become tolerant. Different structures within a bacterium, including its outer wall, are made of specific building blocks like proteins. Stopping the bacterium’s ability to craft these pieces weakens its wall, making it more likely to take damage from the outside environment before it can take the wall down.</p>
<h2>Tolerance and resistance are connected</h2>
<p>Although there has been considerable research on how bacteria develop tolerance, a key piece of the puzzle that has been neglected is how tolerance leads to resistance.</p>
<p>In 2016, researchers discovered how to <a href="https://doi.org/10.1038/nmicrobiol.2016.20">make bacteria tolerant in the laboratory</a>. After repeated exposure to different antibiotics, <em>E. coli</em> cells were able to adapt and survive. DNA, the genetic material containing instructions for cell function, is a fragile molecule. When DNA is damaged rapidly by stress, such as antibiotic exposure, the cell’s repair mechanisms tend to mess up and cause mutations that can create resistance and tolerance. Because <em>E. coli</em> is similar to many different types of bacteria, these researchers’ findings revealed that, ironically, essentially any bacteria can develop tolerance if pushed to their limits by the antibiotics meant to kill them. </p>
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<figcaption><span class="caption">Bacteria form large communities in biofilms.</span></figcaption>
</figure>
<p>Another recent key discovery was that the longer bacteria remain tolerant, the more likely they are to <a href="https://doi.org/10.1073/pnas.2209043119">develop mutations leading to resistance</a>. Tolerance allows bacteria to develop a resistance mutation that reduces their chances of being killed during antibiotic treatment. This is especially relevant to bacterial communities often seen in <a href="https://doi.org/10.2147/IDR.S379502">biofilms that tend to coat high-touch surfaces in hospitals</a>. Biofilms are slimy layers of bacteria that ooze a protective jelly that makes antibiotic treatment difficult and DNA sharing between microbes easy. They can induce bacteria to evolve resistance. These conditions are thought to mimic what could be happening during antibiotic-treated infections, in which many bacteria are living next to one another and sharing DNA. </p>
<p>Researchers are calling for more research into antibiotic tolerance with the hope that it will lead to <a href="https://doi.org/10.1128/mBio.02095-19">more robust treatments</a> in both infectious diseases and cancers. And there is reason to be hopeful. In one promising development, a mouse study found that <a href="https://doi.org/10.1126/science.1211037">decreasing tolerance also reduced resistance</a>. </p>
<p>Meanwhile, there are steps everyone can take to aid in the battle against antibiotic tolerance and resistance. You can do this by <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">taking an antibiotic exactly as prescribed</a> by a doctor and finishing the entire bottle. Brief, inconsistent exposure to a medicine primes bacteria to become tolerant and eventually resistant. Smarter use of antibiotics by everyone can stop the evolution of tolerant bacteria.</p><img src="https://counter.theconversation.com/content/200226/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Keller receives funding from the National Science Foundation Graduate Research Fellowship Program and the National Institutes of Health (NSF GRFP #DGE-1650441 and NIH R01-AI143704)</span></em></p>Antibiotic resistance has contributed to millions of deaths worldwide. Research suggests that any bacteria can develop antibiotic tolerance, and possibly resistance, when pushed to their limits.Megan Keller, Ph.D. Candidate in Microbiology, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2032052023-04-06T12:07:20Z2023-04-06T12:07:20ZDeadly fungus Candida auris is spreading across US hospitals - a physician answers 5 questions about rising fungal infections<figure><img src="https://images.theconversation.com/files/519667/original/file-20230405-14-l85lwf.jpg?ixlib=rb-1.1.0&rect=215%2C32%2C6186%2C3847&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Candida auris is a fungal yeast that can infect humans.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/candida-yeast-and-hyphae-stages-illustration-royalty-free-illustration/1296293760?phrase=candida%20auris&adppopup=true">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p><em>In late March 2023, the U.S. Centers for Disease Control and Prevention highlighted the <a href="https://www.cdc.gov/media/releases/2023/p0320-cauris.html">threat posed by a rapidly spreading fungus</a> called Candida auris that is causing infections and deaths among hospital patients across the country. The unexpected rise of this recently discovered pathogen is part of a larger trend of increasing fungal infections in the U.S.</em></p>
<p><em><a href="https://directory.hsc.wvu.edu/Individual/Index/31722">Arif R. Sarwari</a> is a physician and professor of infectious diseases at West Virginia University. Amid rising concerns among doctors and public health officials, Sarwari helped explain what Candida auris is, how it is spreading and how worried people in the U.S. should be.</em></p>
<h2>1. What is Candida auris?</h2>
<p><em>Candida auris</em> is a recently identified, single-cell fungus that can infect humans and is moderately <a href="https://www.cdc.gov/fungal/candida-auris/index.html">resistant to existing antifungal drugs</a>. You might be familiar with superficial fungal infections – like athlete’s foot or vaginal yeast infections – which are quite common and don’t pose significant risks to most people. In contrast, <em>Candida auris</em> and other related fungi can <a href="https://doi.org/10.2174/1389450120666190924155631">cause infections within a person’s body</a> and are <a href="https://doi.org/10.3390%2Fjof7010031">much more dangerous</a>.</p>
<p><em>Candida auris</em> is a type of yeast that was first identified in 2009 and is one of a number of species in the candida family that can infect people. In the past, most invasive candida infections were <a href="https://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html">caused by <em>Candida albicans</em></a>. Recently, though, infections with species of candida that are much more resistant to drugs than <em>Candida albicans</em> – <a href="https://www.cdc.gov/media/releases/2023/p0320-cauris.html">like <em>Candida auris</em></a> – have shot up, with a nearly <a href="https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html">fivefold increase since 2019</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A person holding an IV line with a patient's arm." src="https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Candida fungi can get into a person’s bloodstream through a contaminated IV line and cause a blood infection.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/checking-a-cannula-royalty-free-image/622263704?phrase=IV%20catheter&adppopup=true">Richard Bailey/Corbis Documentary via Getty Images</a></span>
</figcaption>
</figure>
<h2>2. How dangerous are candida infections?</h2>
<p>For the most part, healthy people do not have to worry about invasive candida infections. There are two groups of people who are <a href="https://doi.org/10.1056/NEJMra1315399">most at risk for dangerous candida infections</a>: first are patients in intensive care units who also have central intravenous catheters and are receiving broad spectrum antibiotics. Patients with weak immune systems, such as cancer patients on chemotherapy or patients with human immunodeficiency virus, are also at high risk of candida infection.</p>
<p>Nearly all people have candida fungi growing in their guts and on their skin as part of their microbiome. When a person is healthy, candida numbers are low, but the fungi can proliferate rapidly and overcome a person’s immune system when a patient is <a href="https://doi.org/10.1016/0195-6701(95)90036-5">sick and on antibiotics</a>. </p>
<p>If candida cells on a person’s skin contaminate an intravenous line, the fungus can get into a patient’s bloodstream and cause often deadly bloodstream infections. Candida species are the fourth most-common cause of <a href="https://doi.org/10.1086/421946">hospital associated bloodstream infections</a>. </p>
<p>There are three classes of antifungal drugs that can be used to <a href="https://doi.org/10.1016/j.idc.2021.03.005">fight invasive candida infections</a>. <em>Candida albicans</em> is susceptible to all three and easier to treat than <em>Candida auris</em>, which is moderately <a href="https://doi.org/10.3947/ic.2022.0008">resistant to all three classes of antifungals</a>.</p>
<h2>3. How common are invasive fungal infections?</h2>
<p>The CDC estimates that in the U.S., around <a href="https://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html">25,000 patients get candida bloodstream infections</a> every year. </p>
<p>Candida bloodstream infections are best understood as a tale of two eras. In the past, they were almost always caused by drug-susceptible <em>Candida albicans</em> that arose endogenously from a patient’s own microbiome. There was no concern about infections spreading to other patients.</p>
<p>The recent emergence of drug-resistant and more transmissible <em>Candida auris</em> is <a href="https://www.cdc.gov/media/releases/2023/p0320-cauris.html">raising alarms</a> among health professionals. Because this species can contaminate surfaces and easily spread from patient to patient, the fungus is causing outbreaks both <a href="https://doi.org/10.1016/j.micpath.2018.09.014">within and between hospitals</a>. </p>
<p><iframe id="H18dQ" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/H18dQ/2/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>4. Why are fungal infections increasing?</h2>
<p>Fungal infections have been rising in the U.S. in recent years, especially infections caused by <em>Candida auris</em>. The pathogen only caused a few infections each year between 2013 and 2016, but starting in 2017, infections began to rise rapidly with <a href="https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html">2,377 confirmed cases recorded in 2022</a> according to the CDC. Deaths caused by all candida infections are rising, too, from 1,010 in 2018 <a href="https://www.cdc.gov/fungal/cdc-and-fungal/burden.html">to nearly 1,800 in 2021</a>.</p>
<p>The reasons for this increase are complicated, but I think there are two main drivers: more, sicker patients in hospitals and a stressed health system, both of which got worse during the COVID-19 pandemic.</p>
<p>Hospitals are seeing more very sick patients with weak immune systems, especially as the population ages. This means there are more susceptible patients at hospitals to begin with. </p>
<p>Additionally, any time the health system is stressed – like during a pandemic – drug-resistant <a href="https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf">bacterial and fungal infections increase</a>. This is because very sick patients are usually in crowded wards and exposed to many antibiotics. In addition, loss of hospital staff and increased workload results in lower quality sanitation - causing more spread of resistant pathogens.</p>
<p>I view the rise of drug-resistant fungi like <em>Candida auris</em> through the same lens as <a href="https://theconversation.com/antibiotic-resistance-is-at-a-crisis-point-government-support-for-academia-and-big-pharma-to-find-new-drugs-could-help-defeat-superbugs-169443">worsening antibiotic resistance</a>. The more antibiotics people use, the greater the chances a resistant strain will become dominant.</p>
<h2>5. What can the medical community do about it?</h2>
<p>There are a few options for fighting the rise of drug-resistant <em>Candida auris</em>. </p>
<p>The most effective measures are <a href="https://www.ncbi.nlm.nih.gov/books/NBK563297/">good infection control practices</a>. These behaviors and protocols include practicing good hand hygiene before and after each patient contact, wearing isolation gowns and gloves that are carefully discarded in a patient’s room, and taking measures to detect <em>Candida auris</em> infections early and isolate patients to prevent the spread. Though relatively simple, these actions are key to preventing the spread of all antibiotic-resistant pathogens, not just fungi.</p>
<p>The second option is to develop better drugs to treat new, antifungal-resistant strains of candida. Many new antifungal drugs are <a href="https://doi.org/10.3390%2Fjof8111144">already under development</a>. However, prevention through sound infection control will always remain foundational, as further drug development is akin to an arms race.</p><img src="https://counter.theconversation.com/content/203205/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arif R. Sarwari does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Candida auris is a relatively new addition to a family of fungi that can infect people. Most of these infections occur in sick, hospitalized patients and can be deadly.Arif R. Sarwari, Professor of Infectious Diseases, West Virginia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1977832023-02-28T13:26:32Z2023-02-28T13:26:32ZOne easy way to fight antibiotic resistance? Good hand hygiene<figure><img src="https://images.theconversation.com/files/512265/original/file-20230224-2018-lwzgz6.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Washing your hands reduces your risk of transmitting and contracting harmful bacteria from other people and the environment.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/female-doctor-uses-hand-santizer-royalty-free-image/1254704741">SDI Productions/E+ via Getty Images</a></span></figcaption></figure><p>Can washing your hands help stop the evolution of antibiotic resistance? Mathematically, <a href="https://doi.org/10.1093/emph/eoac038">it’s possible</a>.</p>
<p><a href="https://medlineplus.gov/antibiotics.html">Antibiotics</a> save lives by killing bacteria that cause infections. But antibiotics don’t just kill infection-causing bacteria or stay in the area of the body where the infection is occurring. Instead, antibiotics spread across the body and inhibit or kill any sensitive bacteria they encounter.</p>
<p>While bacteria that are more sensitive to the antibiotics are killed off, those that are able to survive will continue to reproduce with less competition. This results in increasing abundance of resistant bacteria that can <a href="https://www.cdc.gov/drugresistance/about/how-resistance-happens.html">undermine the effectiveness of the antibiotic</a>. </p>
<p><a href="https://scholar.google.com/citations?user=WcKtVOkAAAAJ&hl=en">I am a researcher</a> who studies the evolution of antibiotic resistance. During my medical training, I was taught about the importance of hospital hygiene practices like <a href="https://www.cdc.gov/drugresistance/protect-yourself-family.html">hand-disinfection</a>. It is well established that good hygiene can help prevent transmission of harmful bacteria from other people or from the environment. I came to wonder how hygiene affects the evolution of antibiotic resistance.</p>
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<a href="https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Nurse washing hands with foamy hand sanitizer from dispenser." src="https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Hand-washing is an essential component of hospital hygiene practices.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/using-hand-sanitizer-royalty-free-image/182440832">nano/E+ via Getty Images</a></span>
</figcaption>
</figure>
<p>So I teamed up with my colleagues <a href="https://portal.research.lu.se/en/persons/magnus-aspenberg">Magnus Aspenberg</a>, <a href="https://portal.research.lu.se/en/persons/sara-maad-sasane">Sara Maad Sasane</a>, <a href="https://scholar.google.se/citations?user=M2HsaIsAAAAJ&hl=sv">Fredrik Nilsson</a> and <a href="https://scholar.google.com/citations?user=ZgN-OgMAAAAJ&hl=en">Sam Brown</a>, experts in mathematics, statistics and microbial evolution, to answer this question. </p>
<p>We built a <a href="https://doi.org/10.1093/emph/eoac038">mathematical model of antibiotic resistance evolution</a>. In this model, resistant and sensitive bacteria compete in the microbial communities living in patients and transmit from one patient to another. We studied the effects of two parameters: hygiene (or use of an alcohol-based hand rub), which limits how much bacteria spreads between patients, and antibiotic use, which selects for resistant bacteria by killing sensitive ones.</p>
<p>We found that hygiene and antibiotic use interact. Antibiotic use had less of an effect on the evolution of antibacterial resistance as hygiene levels increased. This is because evolution toward resistance depends on variation in bacterial sensitivity to antibiotics. By affecting the distribution of resistant and sensitive bacterial strains across patients, hygiene limits the bacterial diversity needed to evolve resistance.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/ZvhFeGEDFC8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The effectiveness of antibiotics is under threat from bacteria rapidly evolving resistance against them.</span></figcaption>
</figure>
<p>Research on the evolution of antimicrobial resistance has focused more on evolutionary selection than hygiene. Most studies investigate, for example, whether a <a href="https://doi.org/10.1371/journal.pcbi.1004689">high or a low dose of a drug</a> is better to prevent resistance. Incorporating hygiene and other interventions into research on antibiotic resistance could help build a more comprehensive understanding of how bacteria evolve to become resistant.</p>
<p>The <a href="https://www.cdc.gov/drugresistance/protect-yourself-family.html">role of good hygiene</a> in preventing illness is already well accepted in practice. Our findings underscore its importance by highlighting the role it plays in the evolutionary process of bacterial resistance.</p><img src="https://counter.theconversation.com/content/197783/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The work was supported by grants from the Wenner-Gren Foundations, the Royal Physiographic Society of Lund (the Fund of the Hedda and John Forssman Foundation), the Sten K Johnsson Foundation, the Crafoord Foundation, the Cystic Fibrosis Foundation, and the Centers for Disease Control and Prevention (BAA 2017-OADS-01).</span></em></p>Using a mathematical model, researchers found that good hygiene can reduce the harmful effects of antibiotic use.Kristofer Wollein Waldetoft, Postdoctoral Fellow in Infection Medicine, Georgia Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2002242023-02-23T21:32:26Z2023-02-23T21:32:26ZThe fungus zombies in ‘The Last of Us’ are fictional, but real fungi can infect people, and they’re becoming more resistant<figure><img src="https://images.theconversation.com/files/511892/original/file-20230223-22-69v4bj.jpeg?ixlib=rb-1.1.0&rect=250%2C14%2C1667%2C1063&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In the HBO series ‘The Last of Us,’ the parasitic fungus cordyeps mutates, and jumps from insects to humans and quickly spreads around the world, rendering its victims helpless to control their thoughts and actions.</span> <span class="attribution"><span class="source">(HBO)</span></span></figcaption></figure><p>Many of the people watching <a href="https://www.hbo.com/the-last-of-us"><em>The Last of Us</em></a> are likely there for the zombies.</p>
<p>I love the zombies too, but I’m really there for the fungus.</p>
<p>I’ve been studying fungi since my PhD work in the 1980s, and I grow more fascinated by these amazing organisms with every passing year.</p>
<p>In the HBO series and the <a href="https://www.playstation.com/en-ca/games/the-last-of-us-part-i/">video game that inspired it</a>, a parasitic fungus — a fictitious mutation of the <a href="https://www.nationalgeographic.com/animals/article/cordyceps-zombie-fungus-takes-over-ants">very real cordyceps</a> — jumps from insects to humans and quickly spreads around the world, rendering its victims helpless to control their thoughts and actions. Far-fetched fungal fear-mongering? It’s definitely fictional, but maybe not as preposterous as it might seem.</p>
<h2>Fascinating fungi</h2>
<p>From microscopic mould spores to <a href="https://www.scientificamerican.com/article/strange-but-true-largest-organism-is-fungus/">kilometres-long mycelium</a> under the forest floor, members of this distinct biological kingdom — neither plant nor animal — are incredible, and highly worthy of more attention.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An ant with fungal growths growing from its head and abdomen, on a green leaf" src="https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512053/original/file-20230223-16-mssl7i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">An ant infected with parasitic cordyceps fungus.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>Most of us may not think about them beyond the mushroom slices on our pizza, but fungi figure prominently in our everyday lives. Do you eat bread? Thank <a href="https://www.britannica.com/science/yeast-fungus">the fungus we call yeast</a>. Do you enjoy beer, wine or whisky? Raise a glass to your <a href="https://doi.org/10.3390%2Fmicroorganisms8081142">fungal friends responsible for the fermentation</a> that brings them to life.</p>
<p>Every time a round of antibiotics helps you recover from some form of infection, remember that <a href="https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html">a mould gave us the compounds that became penicillin</a> and its many derivatives.</p>
<p>Fungi are incredible chemists. They make many compounds that humans cannot easily replicate in the lab. Some make compounds that can affect behaviour. </p>
<p>Look at <a href="https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/lsd">lysergic acid diethylamide</a>, commonly known as LSD, or “acid.” Its well-known psychedelic effects originate from a grain mould. Similarly, “magic” mushrooms are the source of <a href="https://www.canada.ca/en/health-canada/services/substance-use/controlled-illegal-drugs/magic-mushrooms.html">psilocybin</a>. LSD and magic mushrooms are both illegal recreational drugs but are also under study for their therapeutic value.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/albertas-new-policy-on-psychedelic-drug-treatment-for-mental-illness-will-canada-lead-the-psychedelic-renaissance-195061">Alberta’s new policy on psychedelic drug treatment for mental illness: Will Canada lead the psychedelic renaissance?</a>
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<h2>Fungal infections</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pink flower-like blooms on translucent stems" src="https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=566&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=566&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=566&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=711&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=711&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511900/original/file-20230223-2553-wdgm71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=711&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Microscopic image of the fungus Aspergillus fumigatus.</span>
<span class="attribution"><span class="source">(CDC)</span></span>
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<p>Fungi also have an aggressive side. Apart from breaking down dead plants and animals, some forms attack living creatures, including humans. Whole pharmacy shelves are stocked with remedies for <a href="https://www.cdc.gov/healthywater/hygiene/disease/athletes_foot.html">athlete’s foot</a>, <a href="https://www.cdc.gov/fungal/diseases/candidiasis/index.html">yeast infections</a> and <a href="https://www.cdc.gov/fungal/diseases/ringworm/treatment.html">jock itch</a>, all of them nasty fungal infections. Even <a href="https://doi.org/10.1016/j.jaad.2004.10.211">dandruff is caused by a fungus</a>.</p>
<p>Yet while we can access an array of medications to cure bacterial infections such as pneumonia and strep throat, there are only <a href="https://www.healthline.com/health/fungal-infection/antifungal">four known compounds</a> available to rid ourselves of fungal infections. Three are available in the various over-the-counter powders, sprays and ointments we use to treat common fungal infections. </p>
<p>The fourth and newest class, echinocandins, is reserved for hospital settings, where the consequences of fungal infections can be deadly.</p>
<p><a href="https://www.thewrightlab.com/">My team’s research lab</a> at McMaster is part of the university’s broader <a href="https://globalnexus.mcmaster.ca/">Global Nexus for Pandemics and Biological Threats</a>, and also works with the global research organization CIFAR’s <a href="https://cifar.ca/research-programs/fungal-kingdom/">Fungal Kingdom: Threats and Opportunities</a> program. </p>
<p>We are working to find ways to limit the potential harm humans face from fungal infections. We also seek to understand how we can use their abundant and as-yet barely tapped potential to make new antibiotics <a href="https://theconversation.com/antibiotic-resistant-infections-could-destroy-our-way-of-life-new-report-126670">before we lose the waning power of penicillin and its derivatives</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/future-infectious-diseases-recent-history-shows-we-can-never-again-be-complacent-about-pathogens-177746">Future infectious diseases: Recent history shows we can never again be complacent about pathogens</a>
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<h2>Fungi adapt and evolve</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Blue organisms growing from a translucent stalk" src="https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=414&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=414&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=414&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=520&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=520&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512055/original/file-20230223-28-etvxfk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=520&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Microscopic image of the fungal organism, Epidermophyton floccosum, which is a cause of infections such as athlete’s foot and jock itch.</span>
<span class="attribution"><span class="source">(CDC/Libero Ajello)</span></span>
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</figure>
<p>I was first attracted to fungus research as a student about to begin my PhD studies about 35 years ago. At that time, <a href="https://www.hiv.gov/hiv-basics/overview/history/hiv-and-aids-timeline">HIV-AIDS was still emerging</a>, shutting down the immune systems of otherwise healthy people, leaving them vulnerable to opportunistic infections, <a href="https://www.cdc.gov/fungal/infections/hiv-aids.html">including fungal infections</a>.</p>
<p>I wanted to understand more about how fungi worked.</p>
<p>Like bacteria and viruses, fungi are always evolving and adapting, <a href="https://www.who.int/news/item/25-10-2022-who-releases-first-ever-list-of-health-threatening-fungi">finding ways to survive under hostile conditions</a>. We are seeing many forms of fungi adapting to live at ever-higher temperatures, including body temperature, which has long been humans’ first line of defence.</p>
<p>We are also seeing growing antimicrobial resistance among some causes of fungal infection, yeasts such as <a href="https://cifar.ca/cifarnews/2019/04/30/tackling-a-global-superbug/">Candida auris</a> and moulds such as <a href="https://www.cdc.gov/fungal/diseases/aspergillosis/index.html">Aspergillus</a>, both of which can be causes of in-hospital infections.</p>
<h2>Potential for a fungal pandemic</h2>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/E5tSO9aR2Ds?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">In the HBO Max drama ‘The Last of Us,’ a fungal infection turns its victims into fungus-sprouting zombies.</span></figcaption>
</figure>
<p>While <em>The Last of Us</em> is a strictly dramatic projection of what might happen in a deadly fungal outbreak, it is at least based, if not in reality, in logic.</p>
<p>Fungi are able to influence perceptions and behaviour through chemistry. Are they getting closer? You bet. Do they make zombies? Not that we know of, but the thought is darkly entertaining, and that keeps me watching.</p>
<p>The show does do an excellent service by reminding us that we need to adapt to stay ahead of the possibility of a fungal pandemic.</p>
<p>In the same way the movie <em><a href="https://mediashift.org/2017/04/reading-presidents-men-age-trump/">All The President’s Men</a></em> once inspired a generation of journalists, and <em><a href="https://news.harvard.edu/gazette/story/2012/10/the-paper-chase-at-40/">The Paper Chase</a></em> later channelled many eager students toward law school, I am hopeful that <em>The Last of Us</em> may trigger new interest in studying fungi.</p>
<p>The more minds we can focus on unlocking the true magic in mushrooms, the better off we’ll all be.</p><img src="https://counter.theconversation.com/content/200224/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerry Wright receives funding for antifungal research from the Canadian Institutes of Health Research and the Canadian Institute for the Advanced Research and is a consultant for Kapoose Creek, a Canadian biotechnology firm.</span></em></p>While ‘The Last of Us’ is a dramatic projection of a deadly fungal outbreak, it is based, if not in reality, in logic. And it’s a reminder that fungal infections are growing more resistant.Gerry Wright, Professor of Biochemistry and Biomedical Sciences, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1994802023-02-15T15:51:33Z2023-02-15T15:51:33ZAntibiotics are being inappropriately prescribed for COVID, increasing the threat of antimicrobial resistance – research<figure><img src="https://images.theconversation.com/files/510283/original/file-20230215-4579-ie0u3v.jpg?ixlib=rb-1.1.0&rect=25%2C0%2C2800%2C1861&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotics are for bacterial infections – they shouldn't be prescribed to treat viruses.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmasict-serving-customer-drug-store-1857327172">PH888/Shutterstock</a></span></figcaption></figure><p>Antibiotics are drugs designed to treat infections caused by bacteria (for example, skin infections). They don’t work on infections caused by other microbes such as viruses (including COVID and flu) or fungi (for example, thrush).</p>
<p>Beyond treating bacterial infections, antibiotics also have other important uses, like preventing infection <a href="https://www.ecdc.europa.eu/en/publications-data/directory-guidance-prevention-and-control/prudent-use-antibiotics/peri-operative">during major surgery</a>.</p>
<p>Bacteria have existed for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413235/">billions of years</a> and are adept at survival. Since the early 20th century when antibiotics <a href="https://www.sciencedirect.com/science/article/pii/S1369527419300190">were introduced</a> as medicines to fight infections, bacteria have worked out several ways to protect themselves and avoid being killed. </p>
<p>When antibiotics are misused or overused, more opportunities arise for bacteria to develop and improve these protective tools. This contributes to a problem called antibiotic or <a href="https://theconversation.com/antimicrobial-resistance-now-causes-more-deaths-than-hiv-aids-and-malaria-worldwide-new-study-175351">antimicrobial resistance</a>, where bacteria evolve over time so that antibiotics no longer work against them. This makes infections more difficult to treat as doctors have fewer antibiotics to choose from, in turn <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">increasing the risk</a> of serious illness and death. </p>
<p>But how has the COVID pandemic affected antibiotic use, and the problem of antibiotic resistance? A <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00025-1/fulltext">recent study</a> which analysed pharmaceutical sales data from 71 countries suggests that as COVID cases went up, so did antibiotics sales.</p>
<p>The researchers examined <a href="https://www.iqvia.com/solutions/commercialization/brand-strategy-and-management/market-measurement/midas">sales</a> of four antibiotic families commonly prescribed in respiratory infections (cephalosporins, penicillins, macrolides and tetracyclines) from March 2020 to May 2022.</p>
<p>They sourced monthly sales data for these antibiotics per 1,000 people, and from a <a href="https://ourworldindata.org/coronavirus">separate database</a> also gathered data on COVID infections. For comparison, the researchers used global antibiotic sales trends from 2018.</p>
<p>Not surprisingly, they found antibiotics sales fell sharply over April and May 2020. This drop was likely a result of fewer infections spreading while people were under strict lockdown measures, and perhaps some people <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834942/">avoiding healthcare</a>. </p>
<p>However, antibiotic sales gradually increased thereafter. The resurgence of non-COVID respiratory viral infections <a href="https://theconversation.com/qanda-is-the-common-cold-really-much-worse-this-year-170338">with the easing of lockdowns</a> may have contributed to increased antibiotics sales from 2021 onward. By May 2022, sales had returned to just below pre-pandemic levels. </p>
<p>Using statistical models, the researchers found an association between increasing COVID rates and higher antibiotic sales. </p>
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Read more:
<a href="https://theconversation.com/covid-is-caused-by-a-virus-so-why-are-researchers-treating-it-with-antibiotics-171897">COVID is caused by a virus – so why are researchers treating it with antibiotics?</a>
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<h2>COVID and antibiotics</h2>
<p>Research has <a href="https://pubmed.ncbi.nlm.nih.gov/35263322/">previously identified</a> <a href="https://pubmed.ncbi.nlm.nih.gov/35237702/">seasonal spikes</a> in <a href="https://pubmed.ncbi.nlm.nih.gov/22752512/">antibiotic use</a> correlating with the winter virus season. This is concerning because antibiotics are designed to target bacteria, and <a href="https://theconversation.com/why-you-shouldnt-take-antibiotics-for-colds-and-flu-105520">have no effect on viruses</a> such as those which cause colds or flu.</p>
<p>Many antibiotic prescriptions in these cases <a href="https://www.bmj.com/content/364/bmj.k5092">are inappropriate</a>. However, distinguishing viral from bacterial infection can be difficult clinically, especially in the initial stages of infection. This may explain why patients are sometimes started on antibiotics while waiting for laboratory test results.</p>
<p>In certain situations, antibiotics are appropriate. For example, viral lung infections can damage airways and compromise the normal <a href="https://pubmed.ncbi.nlm.nih.gov/32712106/">protective immune responses</a>. This can allow bacteria to attach to airway cells and invade, causing a secondary bacterial infection. </p>
<p>Early in the COVID pandemic, antibiotic prescribing was probably based on previous experience with flu, where rates of secondary bacterial infection had been reported to be <a href="https://pubmed.ncbi.nlm.nih.gov/27232677/">as high as 65%</a>. But as the pandemic progressed, data indicated bacterial co-infection in COVID was <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00025-1/fulltext">less than 10%</a>. Specific antibiotic prescribing guidelines for patients with COVID <a href="https://pubmed.ncbi.nlm.nih.gov/33010444/">were published</a>.</p>
<p>Yet despite increasing evidence that bacterial co-infection in COVID <a href="https://pubmed.ncbi.nlm.nih.gov/32820807/">is low</a>, research has shown antibiotic prescribing among COVID patients has <a href="https://pubmed.ncbi.nlm.nih.gov/35913964/">remained high</a>. This latest study provides further evidence that antibiotics are commonly prescribed to COVID patients. </p>
<figure class="align-center ">
<img alt="A young male pharmacist makes notes on a clipboard." src="https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The study analysed pharmaceutical sales data from 71 countries.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-african-american-man-pharmacist-standing-1456452941">SofikoS/Shutterstock</a></span>
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<h2>Some limitations</h2>
<p>Similar to other large studies on antibiotic consumption, this study uses antibiotic sales data as a proxy for antibiotic use. This sales data is already captured in databases from a number of countries, and is more readily accessible than data on antibiotic prescriptions in many countries, which may not be captured electronically. But because of the nature of the data, we can’t draw any conclusions as to how many of the antibiotics purchased were appropriately prescribed.</p>
<p>Further, data on non-COVID infections, which can impact antibiotic prescribing and rates of resistance, was not included. The pausing of routine childhood vaccination programmes <a href="https://www.sciencedirect.com/science/article/pii/S2214109X2100512X">during the pandemic</a> probably increased bacterial infection risk in some countries, necessitating increased antibiotic prescriptions. This may have contributed to the trends seen. </p>
<p>When interpreting these findings, it’s also important to note that not all continents were represented equally. Some large countries such as Bangladesh were excluded. </p>
<p>Finally, testing protocols vary between countries, so there may have been some inconsistencies in the COVID case data. And access to antibiotics <a href="https://pubmed.ncbi.nlm.nih.gov/26603919/">is inconsistent globally</a>, especially in low- and middle-income countries, which likely impacted some countries’ sales rates. </p>
<h2>The challenge of antibiotic resistance</h2>
<p>Antibiotic resistance is a <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00502-2/fulltext">global threat to public health</a>, impacting humans, animals and the environment.</p>
<p>Inappropriate antibiotic prescribing in COVID could be contributing to the problem. To address this, we need to see more alignment in guidelines and protocols for clinicians, especially linking diagnosis of viral respiratory infections with antibiotic prescribing guidelines. Support for the development of <a href="https://pubmed.ncbi.nlm.nih.gov/31229593/">rapid diagnostics</a> to confirm or rule out <a href="https://www.nature.com/articles/s41598-021-03741-7">co-infection</a> would also give clinicians confidence to avoid antibiotics in some patients. </p>
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Read more:
<a href="https://theconversation.com/coronavirus-pandemic-is-paving-the-way-for-an-increase-in-superbugs-135389">Coronavirus pandemic is paving the way for an increase in superbugs</a>
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<p>More broadly, tackling the issue of <a href="https://fems-microbiology.org/one-health-10-ways-to-tackle-antibiotic-resistance/">antibiotic resistance</a> requires increased public awareness of the issue, enhanced global surveillance of antibiotic use and resistance, improved infection control policies, and better sanitation. </p>
<p>This rests on <a href="https://www.frontiersin.org/articles/10.3389/fcimb.2021.771510/full">a coordinated</a> “<a href="https://www.ecdc.europa.eu/en/publications-data/antimicrobial-resistance-eueea-one-health-response">One Health</a>” approach – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047147/">a joint global effort</a> across a range of sectors to provide solutions for human, animal and environmental health. This strategy should address health inequalities and will require bespoke interventions, especially in lower- and middle-income countries.</p><img src="https://counter.theconversation.com/content/199480/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deirdre Fitzgerald Hughes receives funding from Science Foundation Ireland and the Irish Research Council.</span></em></p><p class="fine-print"><em><span>Fidelma Fitzpatrick does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Antibiotics are a cornerstone of modern medicine, but resistance is a big challenge – and it’s possibly being exacerbated by the COVID pandemic.Fidelma Fitzpatrick, Consultant Microbiologist, Beaumont Hospital, Dublin, Ireland and Professor and Head of Department, Clinical Microbiology, RCSI University of Medicine and Health SciencesDeirdre Fitzgerald Hughes, Senior Lecturer, Clinical Microbiology, RCSI University of Medicine and Health SciencesLicensed as Creative Commons – attribution, no derivatives.