tag:theconversation.com,2011:/africa/topics/antibiotic-alternatives-23013/articlesAntibiotic alternatives – The Conversation2023-11-15T19:04:23Ztag: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:
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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>
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<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">
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<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>
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<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>
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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>
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<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>
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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/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/1114602019-02-20T12:42:51Z2019-02-20T12:42:51ZBig data is being reshaped thanks to 100-year-old ideas about geometry<figure><img src="https://images.theconversation.com/files/259923/original/file-20190220-148523-1w06d1l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Elesey/Shutterstock</span></span></figcaption></figure><p>Your brain is made up of billions of neurons connected by trillions of synapses. And how they’re arranged gives rise to the brain’s functionality and to your personality. That’s why <a href="https://bluebrain.epfl.ch/">scientists in Switzerland</a> recently produced the first-ever digital <a href="https://bluebrain.epfl.ch/op/edit/page-158777.html">3D brain cell atlas</a>, a complete mapping of the brain of a mouse. While this is a colossal achievement, the great challenge now lies in learning to decipher the atlas. And it’s a huge one. </p>
<p>Science is full of this kind of problem: how to turn large amounts of information into useful insight. For many years, researchers relied on mathematics and statistics to explore data. The explosion of large datasets created by digital storage, the internet, and cheap sensors has led to the development of new techniques designed specifically to deal with this “<a href="https://theconversation.com/explainer-what-is-big-data-13780">big data</a>”. </p>
<p>And now there is an emerging new approach based on century-old ideas that’s producing superior tools for understanding certain types of big data. Using the mouse’s brain as an example, its physical shape determines its functionality. But a precise description of this shape, which we now have, doesn’t automatically reveal everything about how the brain works.</p>
<p>Behind the physical shape lies a more abstract shape formed by the interconnections within the brain. Capturing aspects of this shape by applying techniques from the study of what’s known as “topology” can help reveal a deeper understanding of the brain’s functioning. This same guiding principle of using topological techniques on big data also has applications in drug development and other cutting-edge endeavours. </p>
<h2>Topology</h2>
<p>Topology is a branch of modern geometry <a href="https://press.princeton.edu/titles/8722.html">with roots</a> going back to a foundational observation by the Swiss mathematician Leonhard Euler (1707-1783) about polyhedra, 3D shapes with flat faces, straight edges and sharp corners or “vertices”. In 1750, <a href="https://topologicalmusings.wordpress.com/2008/03/01/platonic-solids-and-eulers-formula-for-polyhedra">Euler discovered</a> that for any convex (with all its faces pointing outwards) polyhedron, the number of vertices minus the number of edges plus the number of faces <a href="https://redlegagenda.com/2015/09/23/eulers-polyhedron-formula/">always equals two</a>. </p>
<p>You can apply the same formula to other shapes to get what is known as their Euler characteristic. This number doesn’t change no matter how the shape is bent or deformed. And <a href="https://www.livescience.com/51307-topology.html">topology</a> is the study of these kind of constant properties of shapes.</p>
<p>Topology went through rapid development during the 20th century as a prominent subject in pure mathematics. The researchers who created the subject didn’t have real-world applications on their minds, they were just interested in what was mathematically true about shapes under certain conditions.</p>
<p>Yet some of these ideas from topology that have been around for over 100 years are now finding significant applications in data science. Because topology focuses on constant properties, its techniques make it insensitive to various data inaccuracies or “noise”. This makes it ideal for deciphering the true meaning behind the collected data.</p>
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<img alt="" src="https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/259929/original/file-20190220-148545-1g16rne.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">A knotty problem.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/female-hands-unravel-black-little-headphones-1184333146?src=_nMmjx-52kYA7yDjzv2OLg-2-54">VIKTORIIA NOVOKHATSKA/Shutterstock</a></span>
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<p>You are probably familiar with a common topological phenomenon. Wires placed neatly in your bag in the morning (your earphones or an adapter) have a tendency to produce a horrible mess by midday. A wire is a very simple shape. Whether or not it is knotted is a topological question, and the tendency to arrive at a topological nightmare in your bag is now <a href="https://www.thenakedscientists.com/articles/questions/why-do-wires-tangle">quite well understood</a>. </p>
<p>Millions of years ago, evolution was confronted with a similar problem. <a href="https://www.livescience.com/37247-dna.html">DNA</a> in cells is a molecule composed of two coiled up chains. Each chain is a very long wire, built up from a sequence of small molecules called nucleobases. When a cell divides, these wires unwind, replicate and then coil up again. But just like wires in a bag, the strands of DNA can become tangled, which prevents the cell from dividing and causes it to die.</p>
<p>Special enzymes in the cell called <a href="https://www.sciencedirect.com/topics/neuroscience/topoisomerase">topoisomerases</a> have the task of preventing such a catastrophe. And deliberately disrupting the topoisomerases of bacteria prevents them from spreading and so stops an infection. This means that a better understanding of how topoisomerases prevent the entanglement of DNA could help us design new antibiotics. And since entanglement is a purely topological feature, <a href="https://academic.oup.com/nar/article/36/11/3515/2410103">topological techniques</a> can <a href="https://academic.oup.com/nar/article/47/1/69/5204334">help us do that</a>.</p>
<h2>Drug development</h2>
<p>Topology can also be used to improve the creation of new drugs. Pharmaceutical drugs are chemicals designed to interact with certain cells in the body in a particular way. Specifically, cells have receptors on them that allow molecules of a certain shape to lock onto them, altering the behaviour of the cells. So producing drugs with these shaped molecules enables them to target and affect the right cells.</p>
<p>As it turns out, manufacturing a molecule to have a particular shape is a rather simple process. But the easiest way to get the drug to the target cells is to send them via the bloodstream, and for that, the drug must be water soluble. After a drug with a correct shape is produced, the million pound question is: does it dissolve in water? Unfortunately, this is a very difficult question to answer just from knowing the chemical structure of the molecule. Many drug discovery projects fail because of solubility issues.</p>
<p>This is where topology comes in. “Molecule space” refers to a way of thinking about an entire collection of molecules as a kind of mathematical entity that can be studied geometrically. Having a map of this space would be a tremendous tool for producing new drugs, particularly if the map included landmarks indicating higher chances of solubility.</p>
<p>In <a href="https://jcheminf.biomedcentral.com/articles/10.1186/s13321-018-0308-5">recent work</a>, researchers used topological data analysis tools as a first step to producing such a map. Analysing vast amounts of data linking molecule properties to water solubility, the new approach led to the discovery of new, previously unsuspected, indicators of solubility. This improved ability to produce water-soluble drugs has the potential to significantly shorten the time it takes to create a new treatment, and to make the whole process cheaper. </p>
<p>In more and more realms of science, researchers are finding themselves with more data than they can effectively make sense of. The response of modern mathematicians to meet the <a href="https://ima.org.uk/9104/3rd-ima-conference-on-the-mathematical-challenges-of-big-data/">mathematical challenges of big data</a> is still unfolding – and topology, a theory bound only by the imagination of its practitioners, is bound to help shape the future.</p><img src="https://counter.theconversation.com/content/111460/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ittay Weiss 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>Techniques from topology can help us understand DNA and improve drug development.Ittay Weiss, Lecturer in Mathematics, University of PortsmouthLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1086092018-12-25T19:31:33Z2018-12-25T19:31:33ZCurious Kids: how do ants make their own medicine?<figure><img src="https://images.theconversation.com/files/249916/original/file-20181211-76989-1osz6th.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1597%2C1063&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Not many people realise ants can make their own medicine. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/pimthida/14274220550/in/photolist-nKn7sS-7JD9RL-6FyRLq-nJttup-b9kkAv-pgKkxu-81NL4r-8t8HS3-PtpLVu-aaT5ju-3JMYfF-c2sdMy-2mpkGS-2RhYgP-9ZdNbD-cPtPWE-mcnJTG-edSzqc-7QaDuK-ahXzva-9wTrRL-6WsLLJ-8YDb1w-PPr4jZ-84A7fp-62aW4h-u25jFk-bSBgD8-c2rKpu-GCkP48-bVdnxP-iwfagp-2zCkHP-uFsqzq-a7vk4j-8tJfjz-9vt4Nn-96kb83-6frKUJ-dGMKTu-azJ8mo-HsgQ5-7XF2NZ-9mim9q-d7nL4m-a5KcxE-dDevqs-aqoo4v-L6UD19-7JPVm1">Flickr/Pimthida</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><em>This is an article from <a href="https://theconversation.com/au/topics/curious-kids-36782">Curious Kids</a>, a series for children. The Conversation is asking kids to send in questions they’d like an expert to answer. All questions are welcome: find out how to enter at the bottom. You might also like the podcast <a href="http://www.abc.net.au/kidslisten/imagine-this/">Imagine This</a>, a co-production between ABC KIDS listen and The Conversation, based on Curious Kids.</em> </p>
<hr>
<blockquote>
<p><strong>How do ants make their own medicine? Thank you. – Anuva, age 5, Montreal.</strong></p>
</blockquote>
<p>Wow, what a wonderful question!</p>
<p>Ants are amazing animals. Even though they have brains smaller than a grain of sand, they know how to use chemicals in their environment to make themselves feel better when they are ill. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-why-do-flies-vomit-on-their-food-98555">Curious Kids: Why do flies vomit on their food?</a>
</strong>
</em>
</p>
<hr>
<h2>How ants get sick</h2>
<p>If an ant touches the spores (which are like seeds) of a fungus called <em>Beauveria bassiana</em> the fungus begins to grow inside their bodies. Soon, they grow very sick.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/251153/original/file-20181218-27767-1a9gs3v.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">This moth got very sick and died because of a fungus called <em>Beauveria bassiana</em>, which is the white stuff.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/m_klimes/35401597205/in/photolist-VWjrtB-UGPxxc-eEwepc-sfWdjk">flickr/MK - fotky</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Ants can cure themselves by drinking small amounts of a chemical that kills the fungus. The chemical is called hydrogen peroxide. </p>
<p>Hydrogen peroxide is found in two things many ants love to eat: nectar and honey dew. Nectar comes from flowers and honeydew is a sweet liquid made by tiny insects called aphids. Ants even like to collect aphids and keep them in little aphid farms.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=863&fit=crop&dpr=1 600w, https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=863&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=863&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1085&fit=crop&dpr=1 754w, https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1085&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/251155/original/file-20181218-27764-1p191fn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1085&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 ants are tending to their aphids in their aphid farm.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/52450054@N04/7004744666/in/photolist-bEZ9xL-a5E2Er-6d5XYx-wb6M8J-28TGA-kzAtH-UMRivY-3aQgqf-3zPN4-4RixwY-9PP9Ld-9Bepe8-72WGFP-fqRWfj-eVxHxb-QPQZTB-ehScYY-WnBAGP-Lqy8V-NgsNzf-6q5g4u-Vhd4hJ-2rCNH-TdvJmW-jfG4dm-dHqzrg-i3yrt-nBYwYj-6q5os7-ctaecu-Mr3iG-bfoX2-d1RvCo-4BNYvy-4stNUT-nM7Ras-4Qs68P-9MYYc6-bfoYf-4QwhDC-6STG7Q-pa4eL4-4RMEH5-qvZPt4-drjeLq-6ob9iz-oj3CT2-fV5jP8-ojkive-pbM5rD">Flickr/Judy Gallagher</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Scientists think sick ants in nature sometimes choose to drink nectar or honeydew that contains higher amounts of hydrogen peroxide.</p>
<h2>A science experiment</h2>
<p>You might be wondering how scientists found out that ants can cure themselves by drinking hydrogen peroxide. After all, it is very hard to watch what happens inside a wild ant nest. </p>
<p>The scientists did a very clever experiment where they gave sick ants and healthy ants a choice between honey water that contained hydrogen peroxide and plain honey water. </p>
<p>Sick ants preferred to drink honey water mixed with hydrogen peroxide while healthy ants preferred to drink plain honey water. Sick ants that drank the hydrogen peroxide were more likely to get better than those that drank plain honey water. </p>
<p>This experiment showed that sick ants could choose to eat foods that contained chemicals that helped them fight off the infection.</p>
<h2>Leaf medicine for food fungus</h2>
<p>Leafcutter ants are another type of ant that can use medicine to treat diseases. Leafcutter ants are common in South American jungles, where they can be seen marching in long lines, carrying leaves over their heads like little green umbrellas. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=274&fit=crop&dpr=1 600w, https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=274&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=274&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=345&fit=crop&dpr=1 754w, https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=345&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/251151/original/file-20181218-27764-ngs20c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=345&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Here are some leafcutter ants.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/13007595@N05/2697196419/in/photolist-57kQwx-iUZ2tf-aALtJY-o5CQHQ-6D2T5b-nnjqF7-5Z2r5j-VABeKJ-6AHHai-9M2DfS-oR9wa-dPBzwT-qXRMbg-duueD8-66nwe-dPHcML-qfGtnD-a9Nrsb-Eev8J-64HyBH-4ZDTMN-dT1xRq-qFh7po-pAo4H2-7SZgzX-2Jn4Jy-exYEd-X7oDkX-2bs5NJ-2JhKUz-hXL39Z-j8BRJ6-2JhP14-5WQMyb-9mBgiM-frK4QD-6aCX9s-6RKF9v-mnewER-4mEm9s-4mAidH-5UeS6Z-X3WqWp-6FQNBo-wY7UW-UTzToi-dRbiVS-8WMuhC-U1osnJ-5LBVFw">Flickr/lana.japan</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The ants do not eat the leaves. Instead, they mash them up into a paste and use them to feed a special fungus they keep in little gardens. Fungus gardens are very important to the ant colony as they provide almost all of the colony’s food.</p>
<p>Sometimes the fungus gardens get sick; when this happens, gardener ants get rid of the sickness using a special chemical called an “antibiotic”. Antibiotics work by killing the germs that make animals (including humans) sick. </p>
<p>Of course, leafcutter ants can’t just walk to the doctor’s office or chemist to get their antibiotics. Instead, they grow a special type of bacteria on their bodies. The bacteria makes the antibiotic that cures the fungus when it gets sick. The friendly, antibiotic-making bacteria are white, so gardener ants look as though they have been sprinkled with white powder.</p>
<p>Next time you are sick, just think of the ants and their amazing ant-ibiotics!</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-where-do-flies-sleep-92175">Curious Kids: Where do flies sleep?</a>
</strong>
</em>
</p>
<hr>
<p><em>Hello, curious kids! Have you got a question you’d like an expert to answer? Ask an adult to send your question to us. You can:</em></p>
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<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p><em>Please tell us your name, age and which city you live in. You can send an audio recording of your question too, if you want. Send as many questions as you like! We won’t be able to answer every question but we will do our best.</em></p><img src="https://counter.theconversation.com/content/108609/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tanya Latty receives research grants from the Australian Research Council, AgriFutures Australia, and the Branco Weiss Society in Science fellowship.
</span></em></p>Hydrogen peroxide is a chemical that can kill germs. It is found in two things many ants love to eat: nectar and honey dew.Tanya Latty, Senior Lecturer, School of Life and Environmental Sciences, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/914122018-02-07T17:01:54Z2018-02-07T17:01:54ZAntibiotic resistance fight could get a little help from ants<figure><img src="https://images.theconversation.com/files/205318/original/file-20180207-74470-hweqft.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A giant ant carries a dead fellow in the name of cleanliness.</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Social_immunity#/media/File:Giant_Ant_(Camponotus_gigas)_carrying_a_dead_fellow_(15571767495).jpg">Dupont/Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The world is facing an <a href="https://theconversation.com/what-will-happen-when-antibiotics-stop-working-59938">antibiotics crisis</a>. Due to overuse, many once-powerful drugs are <a href="https://theconversation.com/is-the-antibiotic-apocalypse-nigh-51006">now useless</a> against certain strains of serious bacterial infections. So scientists are <a href="https://theconversation.com/new-class-of-antibiotics-discovered-and-why-there-may-be-more-to-come-36085">on the hunt</a> for new ways to attack harmful microbes.</p>
<p>One possibility is to investigate how other species have evolved ways to defend themselves. A <a href="http://rsos.royalsocietypublishing.org/lookup/doi/10.1098/rsos.171332">new study</a> highlights how most ants, even from small colonies, produce antimicrobial chemicals in their bodily secretions. It also suggests those ants that don’t make these substances are likely to have some other method of controlling bacteria that could be investigated. So perhaps the answer to antibiotic resistance is under our feet.</p>
<p>Like humans, the more than <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001805">12,000 species</a> of ants are all highly social. This behaviour increases the chance that they come into to contact with germs. Comparable to our towns and cities, ant colonies take communal living to the next level, with up to tens of millions of individuals cohabiting in a single nest.</p>
<p>Colony survival depends on worker ants going out into the environment to collect food. Workers return to their densely inhabited nests loaded with food, but also harmful microbes. Returning workers then share their food and their germs through mouth-to-mouth feeding – essentially vomiting <a href="http://www.wired.co.uk/article/ants-throwing-up-hormones-development">into each other’s mouths</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/mACmBbyj3TA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>If this wasn’t enough, the warm, moist conditions in ants’ nests make them ideal nurseries for disease-causing microbes. Finally, the members of almost all ants in a colony are related, so if one ant is susceptible to a germ, <a href="http://rspb.royalsocietypublishing.org/content/243/1306/55">it is likely that many others will be, too</a>.</p>
<p>Despite this longstanding threat of disease, ants are incredibly successful creatures. They dominate some environments and have diversified into thousands of species over <a href="https://phys.org/news/2006-04-ancient-ants-arose-million.html">150m years of evolution</a>. This suggests ants have found ways to deal with the high threat of disease. So what can we learn from them? </p>
<h2>How ants deal with disease</h2>
<p>Scientists have found that ants use a number of tricks to limit disease. Like humans, ants are exceptional cleaners. Many species have efficient waste-removal systems, ensuring diseased waste (including dead ants) is <a href="http://rspb.royalsocietypublishing.org/content/283/1831/20160625">removed from the nest or contained in special chambers</a>. They also regularly clean themselves and each other, and group together to <a href="http://rstb.royalsocietypublishing.org/content/370/1669/20140108">disinfect contaminated ants</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=606&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=606&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=606&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=761&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=761&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205319/original/file-20180207-74479-c26g2o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=761&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">You scratch my back…</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Social_Immunity#/media/File:Lasius_neglectus_grooming.jpg">Pull/Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>But even with good hygiene habits, disease can still be an issue. Ants have evolved ways around this by using their own form of medicine. For example, some ants, when infected, eat toxins such as hydrogen peroxide <a href="http://onlinelibrary.wiley.com/doi/10.1111/evo.12752/abstract">to fight disease</a>. Others collect conifer resin, which they incorporate into their nests <a href="https://www.sciencedirect.com/science/article/pii/S0003347207005660">as a preventative measure</a>. Some species of ant are able to produce formic acid, which combines with the resin to form a <a href="http://onlinelibrary.wiley.com/doi/10.1002/ece3.2834/pdf">potent antimicrobial</a> agent.</p>
<p>We also know that ants also produce their own antimicrobials <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2672.1992.tb01822.x/abstract;jsessionid=937BED2D39EA0DCAA544A751A052043C.f04t03">in bodily secretions</a>. Now researchers have tried to work out what affects how these chemicals are made. In a new study published in the journal <a href="http://rsos.royalsocietypublishing.org/lookup/doi/10.1098/rsos.171332">Royal Society Open Science</a>, researchers from Arizona State University investigated the antimicrobial activity of 20 ant species in the US living in nests with between 80 and 220,000 inhabitants.</p>
<p>The researchers predicted that larger nest species would produce more effective antimicrobials, because of a greater risk of coming into contact with disease. Testing external secretions against <em>Staphylococcus epidermidis</em>, a common bacterium not known to cause disease, showed that 60% of the ant species produced secretions with antimicrobial activity. But, surprisingly, 40% didn’t produce an antimicrobial that could kill the bacterium.</p>
<p>What’s more, species in larger colonies were no more likely to have antimicrobial activity than small colonies. This is surprising as it is generally thought that disease is more likely to be spread in larger colonies. The authors suggest that the 40% of ants without antimicrobial activity have other methods of controlling the spread of bacteria. But we also don’t know if these 40% produce antimicrobial agents that work against other microbes.</p>
<h2>Antibiotics for the future?</h2>
<p>This adds to the idea that ants could well be a good source of new antibiotics. Not only do ants produce their own antimicrobial agents, but they can also encourage other beneficial microbes to grow. For example, researchers recently discovered a bacterium living among one ant species that produces compounds capable of killing harmful bacteria <a href="http://pubs.rsc.org/en/content/articlepdf/2014/SC/C6SC04265A?page=search">resistant to conventional antibiotics</a>, including the common superbug MRSA.</p>
<p>Millions of years of evolution in a high-risk environment have made ants a potential source of vital antimicrobials. These substances still need to be turned into effective drugs and then trialled in humans. But the more we learn about the strategies ants use to fight disease, the more likely we are to uncover new ways to deal with the threat of resistant bacteria and disease.</p><img src="https://counter.theconversation.com/content/91412/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rob Hammond receives funding from NERC and BBSRC.</span></em></p><p class="fine-print"><em><span>Charlie Durant 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>Ants produce their own antimicrobial chemicals to fight bacteria.Charlie Durant, PhD Candidate, Department of Genetics and Genome Biology, University of LeicesterRob Hammond, Lecturer, Department of Genetics and Genome Biology, University of LeicesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/887262017-12-13T10:19:22Z2017-12-13T10:19:22ZReprogramming bacteria instead of killing them could be the answer to antibiotic resistance<figure><img src="https://images.theconversation.com/files/198546/original/file-20171211-27714-gc0b2x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Acinetobacter baumannii</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Changing someone’s genetic programming is easier than you might think. While techniques for <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">altering DNA at the molecular level</a> are becoming more widely used, it’s also possible to simply turn genes on or off without permanently changing the underlying genetic material. That means we can affect the genetic instructions that get sent to an organism’s body by changing its environment or with drugs.</p>
<p>This field of “epigenetics” is already <a href="https://www.theguardian.com/science/occams-corner/2014/apr/25/epigenetics-beginners-guide-to-everything">helping doctors understand</a> how certain diseases work, why exercise can be so beneficial, and how we might be able to alter the aging process. But my colleagues and I are trying to investigate the role of epigenetics in bacteria.</p>
<p>We <a href="https://doi.org/10.3389/fmolb.2017.00077">recently studied</a> a possible way to affect bacterial epigenetics that might be able to stop infections without using antibiotic drugs. And given that many bacteria are <a href="https://theconversation.com/what-will-happen-when-antibiotics-stop-working-59938">becoming resistant to existing antibiotics</a>, that could open up a vital new way of treating disease.</p>
<p>Our study looked at the bacterium <em>Acinetobacter baumannii</em>, which is a major cause of the infections people can catch in hospitals and which kills up to <a href="https://academic.oup.com/femspd/article/71/3/292/475786">70% of people who are infected with it</a>. Antibiotics no longer work on some strains of <em>A. baumannii</em> – and the World Health Organization recently ranked it as the greatest bacterial <a href="http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/">threat to human health</a>.</p>
<p>We do already have some so-called <a href="https://www.ncbi.nlm.nih.gov/pubmed/28337021">antivirulence drugs</a> that don’t kill bacteria but make them harmless so that the body’s immune system can clear them out without leaving any behind to become resistant to the drug. Coming up with a way to affect bacteria’s epigenetics rendering the bugs harmless could help us create new antivirulence drugs that would make a huge contribution to medicine.</p>
<p>To start this process this we first turned to human epigenetics. The <a href="https://www.theguardian.com/science/occams-corner/2014/apr/25/epigenetics-beginners-guide-to-everything">most common way</a> of affecting our epigenetics is to add a small molecular tag to our genetic material that turns on or off a related gene. In particular, we can add a tag known as an acetyl group to an important protein called histone .</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=464&fit=crop&dpr=1 600w, https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=464&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=464&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=583&fit=crop&dpr=1 754w, https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=583&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/198548/original/file-20171211-10977-1niu4ck.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=583&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Adding an acetyl tag to histone.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Figure_16_03_02.png">CNX OpenStax</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Histone organises our 2m-long DNA molecules so that they can fit neatly inside our 100 micrometre-long cells. Adding the acetyl tag is a natural mechanism used by cells to change the way histone interacts with DNA. Adding the acetyl tags normally activates certain genes, meaning they change the way the cell behaves. Failures in this histone modification process are <a href="http://www.sciencedirect.com/science/article/pii/S1874391916304407">linked to cancers</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075976/">cardiovascular diseases</a> and many <a href="https://www.nature.com/articles/nrn3427">neurodegenerative disorders</a>.</p>
<p>Bacterial cells have their own version of histone known as HU, which organises their DNA and is involved in making all its functions work. Bacteria that are referred to as “<a href="http://info.achs.edu/blog/bid/282924/Medical-Terminology-Gram-Positive-vs-Gram-Negative-Bacteria">Gram-positive</a>”, such as the ones in our digestive system that help us break down food, can’t survive without <a href="http://www.caister.com/cimb/v/v13/1.pdf">working HU</a>. And “Gram-negative bacteria”, which are typically the ones that make us ill such as <em>Salmonella enterica</em>, become much less harmful <a href="http://mic.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.046359-0">without HU</a>.</p>
<h2>New drugs</h2>
<p>In <a href="https://doi.org/10.3389/fmolb.2017.00077">our study</a>, we found that adding an acetyl tag to HU significantly affected the way it interacted with the DNA. This means it’s highly likely that such modification makes epigenetic changes, affecting how the bacteria grow and infect other organisms. So if we can create drugs that make these changes to bacterial proteins in this way, we could have a new way of stopping infections. </p>
<p>This is a really important challenge in medicine right now, because bacteria that are resistant to antibiotics kill <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">700,000 people a year worldwide</a>. If we don’t find new treatments, the annual death toll could rise to <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">10 million by 2050</a>.</p>
<p>Once we verify the link between specific epigenetic changes and bacterial infection, we can begin looking for substances that alter bacteria’s epigenetics in this way to make it less harmful. There are already several molecules targeting human epigenetics in a similar way under preclinical development or in <a href="https://blogs.biomedcentral.com/on-biology/2016/09/08/future-epigenetic-drugs/">clinical trials</a>. So a drug that “turns off” bacteria’s ability to cause infections may not be too far away.</p>
<p><em>This article was amended on 15 December 2017 to state that the annual death toll from antibiotic-resistant bactaeria coud rise to 10 million by 2050, not 2025 as originally stated.</em></p><img src="https://counter.theconversation.com/content/88726/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yu-Hsuan Tsai receives funding from Wellcome Trust (200730/Z/16/Z). </span></em></p>Researchers are using epigenetics to find ways to ‘turn off’ bacteria’s ability to cause infections.Yu-Hsuan Tsai, Lecturer in Organic Chemistry, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/765032017-04-24T21:55:21Z2017-04-24T21:55:21ZDiscovered in WWI, bacterial viruses may be our allies in a post-antibiotic age<figure><img src="https://images.theconversation.com/files/166234/original/file-20170421-12655-1u4qoni.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Many in the Western Front contracted haemorrhagic dysentery.</span> <span class="attribution"><span class="source">Wellcome Library, London</span></span></figcaption></figure><p>As we again reflect on the sacrifices our Anzac soldiers, nurses and doctors made during the first world war, another centenary goes by unnoticed by most Australians.</p>
<p>It celebrates a scientific discovery made behind the Western Front, one that might soon affect the health and life of many Australians. Bacteriophages (viruses that attack bacteria) – described by Felix d'Herelle in 1917 – may now be the answer to a world where antibiotics are losing effectiveness.</p>
<h2>Dysentery in the trenches</h2>
<p>Historians record WWI as the first conflict in which more military deaths were attributable to <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61790-6/abstract">hostile action than disease</a>. But the <a href="https://theconversation.com/flies-filth-and-bully-beef-life-at-gallipoli-in-1915-39321">filthy nature of trench warfare</a> on battlefronts like Gallipoli allowed infectious diseases like dysentery to spread widely among troops.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=764&fit=crop&dpr=1 600w, https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=764&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=764&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=960&fit=crop&dpr=1 754w, https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=960&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/166218/original/file-20170421-12633-1ipr8d1.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=960&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Felix d'Herelle led the investigation into the 1915 outbreak.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/en/d/df/Felix_d%27Herelle.png">From the book Gesund durch Viren by Thomas Häusler, 1910. Wikipedia Media</a></span>
</figcaption>
</figure>
<p>Only twice during the <a href="http://www.gallipoli.gov.au/north-beach-commemorative-site/sick-wounded-interpretative-panel.php">Gallipoli campaign</a> did the proportion of Anzac troops being evacuated with wounds exceed those being taken off due to some form of illness.</p>
<p>The situation was scarcely better on the Western Front. In August 1915, ten infantrymen in the French army had contracted severe haemorrhagic dysentery – described as diarrhoea with heavy blood loss. </p>
<p>Investigation of this outbreak was assigned to a young French-Canadian scientist Felix d'Herelle. Working in Paris at the prestigious Institut Pasteur, he quickly isolated and identified the Shigella bacterium as the cause of the infantrymen’s dysentery.</p>
<p>At this critical time during the war, many researchers at the Institut Pasteur practically lived in the laboratory, often working through the night on important scientific pursuits. <a href="http://yalebooks.com/book/9780300071276/felix-dherelle-and-origins-molecular-biology">D’Herelle would sneak in</a> inquisitive side experiments during his rare moments of free time. And it was in these moments he made his great discovery.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=197&fit=crop&dpr=1 600w, https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=197&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=197&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=247&fit=crop&dpr=1 754w, https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=247&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/166238/original/file-20170421-12650-1uezl8z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=247&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">D'Herelle identified the Shigella bacterium as the cause of the infantrymen’s dysentery.</span>
<span class="attribution"><a class="source" href="https://www.cdc.gov/shigella/index.html">Centres for Disease Control and Prevention</a></span>
</figcaption>
</figure>
<h2>Invisible agents</h2>
<p>D’Herelle had a hunch. Previous research had suggested the possibility an invisible agent (possibly a virus) could kill bacteria. To investigate this, he decided to mix filtered (bacteria-free) faeces from dysentery-infected soldiers with a layer of Shigella bacteria he grew in a petri dish. </p>
<p>A day later, d’Herelle saw saw evidence his invisible virus appeared to be killing the bacteria. In 1917, d’Herelle <a href="http://www.tandfonline.com/doi/pdf/10.4161/bact.1.1.14941">published an article</a> in the proceedings of the French Academy of Sciences. Its title translated from French was “On an invisible microbe antagonistic to dysentery bacilli”.</p>
<p>Suspecting a virus but unable to prove these agents killed the bacteria, d’Herelle gave the antagonistic agents the name <a href="http://bio.classes.ucsc.edu/bio105l/EXERCISES/PHAGE/dH.pdf">bacteriophage</a> (from the Greek “phagein”, meaning to eat).</p>
<h2>The rise and fall of bacteriophage therapy</h2>
<p>Before antibiotics were developed in 1945, bacterial infections such as pneumonia and tuberculosis were among the <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4829a1.htm">leading causes of death in industrialised societies</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/166222/original/file-20170421-12665-y0m138.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"></a>
<figcaption>
<span class="caption">Scientific understanding of bacteriophages and biology at the time was limited.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/ajc1/6242867833/in/photolist-avEk7i-dBJ99c-wYT9Q-qJvuek-u12SG-drFewt-bwwd9B-Pmv7L-o39zRq-7PfoQs-geCCe8-9vELdj-GLSvz-J4E9R-GtA4Y-2aY77G-osrTSf-6eStNk-EShVp-qGyJ1h-9RPVKW-8i9cg7-cAkkA3-mtZJCx-q5q8P9-jBZuRe-9eaXqf-Qr2yx-4BHpGL-bVg578-9CN8DV-iPViKR-wRa3kn-a89MBq-agubN5-9Td3aU-nfNUXu-Fdvktk-ng4QDj-EC7Es-4eFiQN-BybXZr-nw2nuA-neNggw-nfaFH6-ntXeN7-F8eN6-nf6in2-nw2Eis-J4dpa">AJC1/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>D’Herelle pioneered bacteriophage (phage) therapy in the 1920s and 1930s to <a href="http://europepmc.org/articles/PMC2542891">successfully treat</a> a range of bacterial infections. These included skin and eye infections, septicaemia and intestinal diseases. The therapy was administered to patients orally, by injection or even through the general water supply.</p>
<p>But the use of phage therapy did not persist. Scientific understanding of bacteriophages and biology at the time was limited. Perhaps the most notable problem was that viruses remained invisible to human eyes until the electron microscope was <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02250-9/abstract">developed in the late 1930s</a>. </p>
<p>It was also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542891">speculated</a> D’Herelle’s work on bacteriophages did not achieve greater prominence as he was regarded as a scientific outsider who allegedly had a tendency for hostility rather than persuasion.</p>
<p>Nevertheless, from the 1940s, d'Herelle’s bacteriophage techniques were used to unravel many molecular processes of genetics, leading to multiple Nobel prizes. But with the meteoric rise of antibiotics in treating bacterial diseases <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109405">from 1945 onwards</a>, use of bacteriophages to treat bacterial infections was largely forgotten.</p>
<h2>The post-antibiotic era</h2>
<p>We have now entered a new era in which the World Health Organisation <a href="http://www.who.int/mediacentre/news/statements/2011/whd_20110407/en/">has declared</a> antibiotic resistance a global health priority. Antibiotics can no longer be relied on to halt the spread of bacterial infections.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/166225/original/file-20170421-12629-qs6mos.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">The World Health Organisation has declared antibiotic resistance a global health priority.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/us-mission/6946430257/in/photolist-bzQgGV-a7DyaQ-787EzG-9Ji7mk-a7Amwe-8FgYP6-7jTFUo-nmDuL2-cPJT3w-7jTisA-6zgUXA-d79ZWm-phbmfo-fPxGqz-6JEhr3-9M2DUT-8YRkJP-7jTFDu-9J42FX-8Fk8Vj-eapSfS-34Gqaf-34C8sg-Rcsrzw-cgbt1-pLJmYM-d79SjE-9NGKrb-6JEhr7-9NEtYQ-5Tk4VE-d1VENG-qZVqNi-nmdjBX-9NJybd-9NDrQR-9NGabs-9NEwpU-ejTVyX-nCqdTV-46uZse-7jPDre-ab95jd-nqBv1N-Sa23t1-nmdwsG-9NAsCc-9dBhot-nM2D4K-8MneV3">United States Mission Geneva /flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The Australian government’s <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-amr.htm#tocstrategy">Antimicrobial Resistance Strategy</a> recognises “the single most powerful contributor to resistance is the global unrestrained use of antibiotics”.</p>
<p>As antibiotic resistance continues to spread, we are seeing the emergence of the century-old infections and diseases suffered by Anzac troops during WWI. </p>
<p>Bacterial infections routinely prescribed and treated with antibiotics are <a href="https://theconversation.com/explainer-what-are-superbugs-and-how-can-we-control-them-44364">transforming into superbugs</a> that threaten to send us back to a pre-antibiotic era. In recent years, strains of Shigella bacteria have re-emerged with broad-spectrum antibiotic resistance in industrialised societies such as <a href="https://www2.health.vic.gov.au/about/news-and-events/healthalerts/increased-antibiotic-resistance-for-shigellosis">Australia</a> and the <a href="https://www.cdc.gov/media/releases/2015/p0402-multidrug-resistant-shigellosis.html">United States</a>. </p>
<p>It’s worth noting that in the world’s poorest communities – where access to clean water and basic sanitation is lacking – dysentery was never defeated. <a href="https://wwwnc.cdc.gov/eid/article/16/11/09-0934_article">Shigella infects</a> hundreds of millions of people each year, and thousands die.</p>
<h2>Making a comeback</h2>
<p>But the future is not altogether bleak. Easy access to DNA sequencing technology is expanding our understanding of the microbial worlds that surround us. And there is a renewed interest in bacteria’s most ancient enemy, and d’Herelle’s important discovery, the bacteriophage. </p>
<p>Some of the original phage therapy techniques he developed have been <a href="https://theconversation.com/soviet-era-treatment-could-be-the-new-weapon-in-the-war-against-antibiotic-resistance-57836">maintained</a> in the former Soviet republic of Georgia, to treat recalcitrant infections such as Golden Staph caused by the bacterium <em>Staphylococcus aureus</em>. </p>
<p>These bacteriophage preparations <a href="https://www.phagetherapycenter.com/pii/PatientServlet?command=static_compassionate&secnavpos=6&language=0">can be imported</a> into Australia for personal use. Yet we previously had little use for them because antibiotics worked, and worked well.</p>
<p>This is changing as scientists, doctors and businesses are leveraging decades of bacteriophage research in a renewed attempt to combat antibiotic-resistant superbugs.</p>
<p>Australia is a growing hotspot for bacteriophage research, investment and <a href="http://www.ampliphibio.com">biotech companies</a>. Scientists at Flinders University are already <a href="http://news.flinders.edu.au/blog/2016/04/26/virus-therapy-to-attack-superbugs/">using bacteriophages</a> to combat bacterial diseases, including Golden Staph. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/166230/original/file-20170421-12650-fcg17q.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">Australia is a growing hotspot for bacteriophage research.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/success">from www.shutterstock.com</a></span>
</figcaption>
</figure>
<p><a href="https://thebarrlab.org">My laboratory</a> is expanding on a <a href="http://www.pnas.org/content/110/26/10771">2013 discovery</a> which described the role bacteriophage viruses play in protecting our bodies from disease-causing bugs. </p>
<p>This unlikely symbiotic partnership is explained for a mainstream audience in a graphic novel (which I co-authored) called <a href="https://theinvisiblewar.com.au">The Invisible War</a>. It is set in the trenches of the first world war, featuring dysentery-ridden nurses, warring microbes and heroic viruses.</p>
<h2>Lest we forget</h2>
<p>Scientists from all over the world are gathering <a href="http://www.bacteriophage100.org/">this week</a> at Paris’s Institut Pasteur to commemorate the 100-year anniversary of the discovery of bacteriophages, made behind the Western Front. </p>
<p>So when remembering our troops, doctors and nurses this Anzac Day, consider also tipping your hat or your glass to the vital role bacteriophages play in our world. One day our health might just depend on them.</p>
<hr>
<p><em>This article was co-written with Dr Gregory Crocetti from <a href="http://scalefreenetwork.com.au/">Scale Free Network</a>.</em></p><img src="https://counter.theconversation.com/content/76503/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy J. Barr receives funding from the Australia Research Council and is a member of the Australian Society for Microbiology.</span></em></p>When commemorating our troops, doctors and nurses this Anzac Day, consider also tipping your hat to the discovery of bacteriophages. In the post-antibiotic era, our health might just depend on them.Jeremy J. Barr, Lecturer in School of Biological Sciences, Microbiology, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/603152016-06-07T02:22:40Z2016-06-07T02:22:40Z‘Antibiotic stewardship’ to keep superbugs at bay just isn’t happening<figure><img src="https://images.theconversation.com/files/125296/original/image-20160606-25985-x0nrui.jpg?ixlib=rb-1.1.0&rect=0%2C193%2C816%2C565&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Everyone says the solution to antibiotic-resistant superbugs is to use antibiotics less often – but it's not happening.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/pennstatelive/5654410503/">Penn State/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><a href="https://www.washingtonpost.com/news/to-your-health/wp/2016/05/26/the-superbug-that-doctors-have-been-dreading-just-reached-the-u-s/">Panic has spread</a> with the discovery of a bacterium, <em><a href="http://aac.asm.org/content/early/2016/05/25/AAC.01103-16.full.pdf+html">Escherichia coli</a></em>, in the United States that is resistant to the last bastions of antibiotics.</p>
<p>This “superbug”, which causes many common infections such as urinary tract infections, cannot be treated with the antibiotic colistin. This is the treatment usually reserved for life-threatening bacterial infections that are resistant to other antibiotics in our arsenal.</p>
<h2>Why is this case so concerning?</h2>
<p>Bacteria <a href="http://www.ars.usda.gov/alternativestoantibiotics/PDF/publications/MolMechAntibiotResistNRM2014.pdf">have shown many cunning ways</a> of resisting the killing power of even our newest antibiotics. International health authorities and health-care providers have been tackling this growth in resistance for some time now. In 2014 the <a href="http://phys.org/tags/antibiotic+resistance/">World Health Organisation</a> labelled it “a major risk to public health”. </p>
<p>Since the <a href="https://www.niaid.nih.gov/topics/antimicrobialresistance/examples/mrsa/Pages/history.aspx">discovery of “superbugs”</a> in humans in 1968, the rise of the multi-resistant (resistant to most available antibiotics at the time) golden staph resulted in public outcry and the enhancement of efforts to use antibiotics more wisely. This is also the case for <a href="http://www.who.int/mediacentre/news/notes/2006/np23/en/">multi-resistant tuberculosis</a>. This disease requires very toxic antibiotics and, despite some success with new antibiotics, has a <a href="http://erj.ersjournals.com/content/44/1/23.short">high death rate</a>.</p>
<p>In the case of staph, there were concerted international efforts to find new antibiotics, which temporarily allowed these serious infections to be treated. Despite these advances, staph remains a major risk for hospital-acquired infections, especially in the setting of surgery or patients with immune suppression.</p>
<p>Since then, we have unfortunately seen antibiotic resistance spread to many other bacteria. In fact, for every antibiotic discovered since the early days of penicillin, the bacteria have found ways to overcome their effects. Many bacteria today have multiple resistance mechanisms.</p>
<p><em>Escherichia coli</em> belongs to a group of bacteria called “gram-negative organisms”. This group is responsible for many of the serious infections found in our most critically ill patients in intensive care. Gram-negative bacteria are particularly prone to developing and sharing resistance genes via “plasmids”, which bacteria use to share information.</p>
<h2>Why isn’t ‘stewardship’ of antibiotics happening?</h2>
<p><a href="https://en.wikipedia.org/wiki/Antimicrobial_stewardship">Anti-microbial stewardship</a> is the main solution that has been put forward for the last two decades. This involves the prudent use of antibiotics to ensure they are used only in cases where they are necessary and in the most efficient way so as to avoid overuse. While this sounds good in principle, it is more complex to implement in practice as there are many barriers to successful antibiotic stewardship. </p>
<p>The restricted use of certain antibiotics needs to spread to all sectors including farming, where the development of resistance in <a href="http://cid.oxfordjournals.org/content/early/2016/04/11/cid.ciw118.abstract">animals can spread to humans</a>. It also needs to be a global effort, as global traffic today makes it very plausible that resistant bacteria can travel too, often in patients who may not even be aware they are ill. </p>
<p>The public and medical community need to partner in the avoidance of antibiotics unless there is indication they are necessary. Often the fear of serious infections leads to the over-use of antibiotics. Adherence to the treatment program is also important. This concerted effort is what makes stewardship so difficult.</p>
<h2>How do we tackle this problem before it’s too late?</h2>
<p>The <a href="http://www.who.int/bulletin/volumes/93/4/15-030415/en/">World Health Organisation estimates</a> 50% of all antibiotics consumed globally are used to treat or prevent infections in animals. These antibiotics make their way into the public as residues in the food consumed or during preparation in contaminated food products. </p>
<p>In 1969, <a href="http://hansard.millbanksystems.com/commons/1969/nov/20/use-of-antibiotics-in-animal-husbandry">the Swann Report</a> raised the concern of the widespread use of antibiotics in farming. In 2003, the Institute of Medicine issued a warning that sub-therapeutic doses of antibiotics in animal feed can <a href="https://thebigceci.wordpress.com/tag/swann-report-1969/">cause resistant bacteria</a> to develop. </p>
<p>The problem is widespread. Chicken, pork and farmed fish receive antibiotics such as tetracyclines that are also used to treat infections in humans, and antibiotics like avoparcin that cause cross-resistance to similar antibiotics used in humans. </p>
<p>In October 1999, the Joint Expert Technical Advisory Committee on Antibiotic Resistance <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/health-pubs-jetacar-cnt.htm/$FILE/jetacar.pdf">report outlined</a> the size of the problem in Australia. After multiple committees, working groups, implementation groups and multiple summits, there has been only partial movement on some of the recommendations and no progress on <a href="http://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Finance_and_Public_Administration/Completed_inquiries/2010-13/jetacar/report/index">several key recommendations</a>. </p>
<p>In 2000, Denmark <a href="http://www.ahi.org/issues-advocacy/animal-antibiotics/the-antibiotic-ban-in-denmark-a-case-study-on-politically-driven-bans/">banned antibiotic use in agriculture</a>. There are lessons to be learnt from the Danes’ success.</p>
<p>More recently, there’s been policy noise from lobby groups looking to <a href="https://www.washingtonpost.com/news/to-your-health/wp/2015/12/17/fight-against-superbugs-gets-dramatic-funding-boost-under-spending-plan/">enhance public health efforts</a> and funding to develop new options to treat and prevent multi-resistant infections.</p>
<p>Researchers around the world are looking at innovative ways to tackle the problem. New antibiotics are unlikely to solve the problem unless new antibiotic classes are developed. This is unlikely if one looks at <a href="http://www.biocentury.com/antibioticsncepipeline.htm">current medications in development</a> by pharmaceutical companies. Only a handful of drugs will be reaching the market in the next decade, and most will be similar to existing antibiotics. </p>
<p>There are economic barriers to antibiotic development, with pharmaceutical companies opting instead for the lucrative markets of oncology and chronic diseases.</p>
<p>New approaches include enhancing the <a href="http://phys.org/news/2016-02-major-breakthrough-antibiotic-resistance.html">killing capacity of the immune system</a> for certain bugs. Lessons from cancer research have shown us the immune system can sometimes be “paralysed” by certain bacteria, such as Legionella. If the system can be tweaked with targeted drugs, then the body’s own immune system will help fight the infection.</p>
<p>Another option is to optimise the choice of antibiotic through more accurate and reliable testing in patients with suspected infections. This will allow doctors to choose their antibiotics more wisely. If doctors are able to use tests that pinpoint the bug causing a patient’s infection, they will be able to use the right antibiotic and thus reduce the chances of resistance.</p>
<p><a href="http://www.amr-review.org/">Innovative research</a> will require <a href="http://www.sciencemag.org/news/2016/05/long-awaited-report-outlines-how-fight-antimicrobial-resistance-and-how-pay-it">appropriate government support</a>.
So far we have been <a href="http://www.abc.net.au/news/2016-04-28/antibiotic-resistance-explained-why-your-decisions-matter/7339062">relatively spared</a> multi-resistant organisms, but for how long? This remains everyone’s problem to solve.</p><img src="https://counter.theconversation.com/content/60315/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sergio Diez Alvarez is affiliated with the Clinical Execellnce Commission Antimicrobial Stewardship Comittee</span></em></p>Panic has spread with the discovery of a bacterium in the United States that is resistant to the last bastions of antibiotic resistance.Sergio Diez Alvarez, Director Of Medicine, The Maitland and Kurri Kurri Hospital, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/538552016-03-21T10:12:46Z2016-03-21T10:12:46ZFighting superbugs with nanotechnology and light<figure><img src="https://images.theconversation.com/files/114996/original/image-20160314-11277-1jdarwf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A quantum dot: A high-resolution transmission electron micrograph of cadmium telluride nanoparticles. (The scale bar in the lower right is 2 nanometers long, or two millionths of a millimeter.)</span> <span class="attribution"><span class="source">Nagpal Group, University of Colorado</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>A new tool is emerging in the fight against antibiotic-resistant bacterial disease. Beyond the global efforts to limit overuse and abuse of antibiotic drugs, nanomedicine is finding additional ways to attack these superbugs.</p>
<p>Nanoparticles, a million times smaller than a millimeter, are proving to be stable, easy to deliver and readily incorporated into cells.</p>
<p>In recent work, a group of researchers at the University of Colorado, of which I am a member, has used nanoscale quantum dots – minuscule semiconductor particles with specific light-absorption properties – to <a href="http://www.nature.com/nmat/journal/vaop/ncurrent/full/nmat4542.html">kill drug-resistant superbugs</a> without harming the surrounding healthy tissue. </p>
<p>Once introduced into the body, the quantum dots do nothing until they are activated by having a light shined on them. Any visible light source (a lamp, room light or even sunlight) can be used for this. So far our research has focused on topical infections on the skin; deeper inside the body, brighter lights or more nanoparticles may be needed.</p>
<p>When activated by light, the quantum dots start generating electrons that attach to dissolved oxygen in the cells, creating radical ions. Those ions interrupt biochemical reactions which cells rely on for communication and basic life functions. In this way, we can target and kill very specific bacterial cells that cause illnesses.</p>
<h2>The superbug threat</h2>
<p>Antibiotics are used not just to treat active bacterial infections; they are also routinely given to patients undergoing surgery, and people with compromised immune systems from diseases like HIV and cancer.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=229&fit=crop&dpr=1 600w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=229&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=229&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=288&fit=crop&dpr=1 754w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=288&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=288&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">What a superbug looks like: A modified atomic-force micrograph of multi drug-resistant E. coli.</span>
<span class="attribution"><span class="source">Nagpal Group, University of Colorado</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Bacteria that are resistant to more than one antibiotic drug – or “superbugs,” as they are commonly called – infect <a href="http://www.cdc.gov/drugresistance/">more than 2 million Americans a year</a>, and kill 23,000 of them. Globally, they <a href="http://amr-review.org/">kill more than 700,000 people</a> each year.</p>
<p>Projections by a <a href="http://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf">United Kingdom government research panel</a> suggest that if unchecked, superbugs could <a href="http://www.scientificamerican.com/article/antibiotic-resistance-will-kill-300-million-people-by-2050/">kill more than 10 million people each year by 2050</a>. That would far outpace all other major causes of death – including diabetes, cancer, diarrhea and road accidents. The economic cost is estimated at <a href="http://amr-review.org/">US$100 trillion</a> by 2050.</p>
<h2>Focusing on a target</h2>
<p>There are other nano-scale medicines for fighting infectious bacteria. When exposed to light, they heat up, killing all cells around them – not just the <a href="http://www.etp-nanomedicine.eu/public/about-nanomedicine/nanomedicine-applications/nanomedicine-in-cancer">disease-causing ones</a>. They therefore require special tools such as proteins or antibodies that selectively stick to desired cell types, to deliver them to very specific locations. That in turn requires the ability to accurately identify target cells.</p>
<p>Our method is an improvement because it allows more specific targeting of cells to be treated. Quantum dots with different sizes and electrical properties can help create different disruptive ions. That can allow doctors to choose disruptors to kill invading bacteria without harming nearby healthy tissue.</p>
<p>The activated quantum dots upset the balance of chemical processes, called “reduction-oxidation” or “<a href="http://www.wiley.com/college/boyer/0470003790/reviews/redox/redox.htm">redox</a>” for short, in disease-causing bacteria in order to kill them.</p>
<p>Using this method and only a normal light bulb, we were able to eliminate a broad range of antibiotic-resistant bacteria. The bacteria were provided to us in the form of actual clinical samples from the <a href="http://www.ucdenver.edu/academics/colleges/medicalschool/Pages/somWelcome.aspx">University of Colorado School of Medicine</a>. They included some of the most dangerous drug-resistant infections: methicillin-resistant <em>Staphylococcus aureus</em>; extended-spectrum β-lactamase-producing <em>Klebsiella pneumoniae</em> and <em>Salmonella typhimurium</em>; multi-drug-resistant <em>Escherichia coli</em>; and carbapenem-resistant <em>Escherichia coli</em>. </p>
<p>We were also able to make nanoparticles with different reactions to light, including having no response or even improving cellular reproduction. Increasing the growth of superbugs is not desirable, but this discovery may allow us encourage the growth of useful bacteria, such as in <a href="http://www.biotopics.co.uk/microbes/penici.html">bioreactors</a>, which can help manufacture of biofuels and antibiotic drugs.</p>
<h2>Taking the next steps</h2>
<p>So far our work has been in test tubes in controlled labs; our next step is to study this technique in animals. If successful, this technology could boost the fight against multi-drug-resistant bacteria in the short term and well out into the future.</p>
<p>It might, for example, spur the creation of a new class of light-activated drugs, lead to development of special fabrics with LED lights for phototherapy, and even form the basis of self-disinfecting surfaces and medical equipment.</p>
<p>And while the bacteria will continue to evolve to seek survival, our ability to control the specific reaction of the quantum dots once activated could let us move more quickly in this fight where defeat is not an option.</p><img src="https://counter.theconversation.com/content/53855/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prashant Nagpal receives funding from National Science Foundation and William M. Keck Foundation.</span></em></p>Quantum dots - minuscule semiconductor particles with specific light-absorption properties - can kill drug-resistant superbugs without harming the surrounding healthy tissue.Prashant Nagpal, Assistant Professor of Chemical and Biological Engineering, University of Colorado BoulderLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/486552015-12-09T03:22:57Z2015-12-09T03:22:57ZUse them and lose them: finding alternatives to antibiotics to preserve their usefulness<figure><img src="https://images.theconversation.com/files/98047/original/image-20151012-17809-p4imw7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tea tree oil instead of antibiotics?</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/jcorduroy/2989463961/">Flickr/Jay Malone</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>For the past decade we’ve consistently heard antibiotics <a href="http://www.bbc.com/news/health-34857015">don’t work as well</a> as they used to. Bacteria are becoming increasingly resistant to their effects and <a href="http://www.theaustralian.com.au/news/world/antibiotic-resistance-is-humanitys-greatest-threat/story-fnb64oi6-1227624524215">we are approaching a time</a> when many bacteria could be <a href="http://www.nature.com/nrmicro/journal/v13/n1/abs/nrmicro3380.html">resistant to all the antibiotics</a> we have.</p>
<p><a href="http://www.theaustralian.com.au/news/world/antibiotic-resistance-is-humanitys-greatest-threat/story-fnb64oi6-1227624524215">Apocalyptic premonitions</a> of the post-antibiotic era aside, what is being done about it? The World Health Organisation recommends a number of different <a href="http://www.who.int/drugresistance/events/Oslomeeting/en/">measures</a>. High on the list is renewing efforts to discover and develop blockbuster agents that can combat these new “superbugs”.</p>
<p>Lower down the list are recommendations about how to use antibiotics more responsibly. This means having <a href="https://theconversation.com/we-need-more-than-just-new-antibiotics-to-fight-superbugs-44054">strategies in place</a> to help preserve the remaining effective antibiotics.</p>
<p>Any use of antibiotics encourages exposed bacteria to develop ways of becoming resistant. Exposing bacteria to antibiotics pressures them to adapt to the antibiotics in an “adapt or die” life and death saga. This is called <a href="http://www.niaid.nih.gov/topics/antimicrobialresistance/understanding/pages/causes.aspx">selection pressure</a>. </p>
<p>Bacteria under threat from antibiotics eventually come up with a way of overcoming their vulnerability. They may develop thicker or more repellent membranes to stop antibiotics from getting into the bacterial cell in the first place. Bacteria may switch on or turn up pumps to expel any antibiotic that does get into the cell. These are just some of the tricks they have to become antibiotic resistant.</p>
<p>Part of ensuring we preserve the antibiotics we have left is to reduce the development of resistance. One way to do this is by replacing antibiotics with agents that kill micro-organisms, but aren’t actually antibiotics. These are called non-antibiotic antimicrobials.</p>
<h2>Non-antibiotic bacteria killers</h2>
<p>Antibiotics are chemicals that can inhibit the growth of, or kill, bacteria. They generally have one way to inhibit or kill bacteria and can usually be taken internally, say orally or intravenously. They are toxic only to bacteria and not to the patient.</p>
<p>Like antibiotics, non-antibiotic antimicrobials also inhibit and kill bacteria. However, unlike antibiotics, they often have multiple ways of killing or inhibiting bacteria, and are often toxic if ingested. They are frequently limited to topical applications such as creams and ointments. Antiseptics are classic non-antibiotic agents.</p>
<p>Many antibiotics are used topically to prevent infections such as those on the skin. While they do this quite effectively, exposing bacteria to antibiotics encourages the processes that lead to antibiotic resistance. Using non-antibiotic antimicrobials instead of antibiotics can help reduce antibiotic resistance.</p>
<h2>Some non-antibiotics</h2>
<p><strong>Honey</strong></p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99254/original/image-20151021-15414-1txmy17.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">Honey - natural and effective.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/bionicgrrl/3535805377/in/photolist-6orVKF-9AKUR9-obrupc-nFtjjy-oiSH8M-8DMzjx-6egY9U-aZQswr-5T6Ysb-4Aq4Eu-e9dZGo-dZc5a8-nY2cQn-cb4WtC-fCADiP-rpEwWp-4p9z4w-oUPcaH-bMcKJ6-oavaJK-bVsrT-6tugy9-6fuSqF-o9TMLA-5fGrsM-pkYegn-tFqsrF-geqSxG-Mf3wF-cv5Mx7-6U3vQV-dGcBKE-7cwWnx-6FD55A-kW2Qv-dK5Ecp-5VHdxU-ad5wEx-5y9Crx-phMJVK-nEuoSm-7Y8nRa-fSmgUz-4UzSUs-bu2Uur-bFwxrV-79LXDr-bHvaEM-BTwgU-msVLvz">Bionicgrrrl/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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</figure>
<p>As part of <a href="http://www.hindawi.com/journals/ecam/2015/261425/">a larger study</a> into keeping dialysis patients healthy, researchers found medical-grade honey was as effective as a topical antibiotic cream they had used around catheter sites to stop infections starting. They also noted that the level of resistance to the antibiotic they previously used declined once they stopped using it.</p>
<p><strong>Mannose</strong></p>
<p>Recent trials in humans (see <a href="http://www.ncbi.nlm.nih.gov/pubmed/23633128">here</a> and <a href="http://onlinelibrary.wiley.com/doi/10.1111/bju.12492/full">here</a>) have suggested that mannose, a type of sugar similar to glucose, may be useful in the treatment of urinary tract infections. Mannose, found in many fruits and vegetables, was found to render bacteria incapable of attaching to the cells of the urinary tract.</p>
<p><strong>Trisodium citrate</strong></p>
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<a href="https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99255/original/image-20151021-15451-10rmhnt.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 simple salt.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/pagedooley/2769134850/">Kevin Dooley/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Doctors working with kidney dialysis patients in the 1990s identified a simple salt, trisodium citrate, that could help keep the patients’ catheters (thin tubes inserted into the skin to drain fluid or administer drugs) from becoming blocked. A secondary effect, serendipitously observed later, was that its use also led to lower rates of infection. </p>
<p>In the almost two decades since, and largely through the efforts of non-commercial interests, trisodium citrate has become one of the main strategies used globally for preventing catheter-related bloodstream infections in dialysis patients.</p>
<p><strong>Tea tree oil</strong></p>
<p>Tea tree oil <a href="http://cmr.asm.org/content/19/1/50.full.pdf+html">inhibits and kills</a> a wide range of bacteria and is safe for topical use. Tea tree oil has also been found to be effective against some antibiotic-resistant bacteria.</p>
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<a href="https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=451&fit=crop&dpr=1 600w, https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=451&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=451&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/98046/original/image-20151012-17831-1kpn6ck.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>
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<span class="caption"></span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/badlydrawn/4685088481/in/photolist-891izB-PJHm6-7cvviJ-phn6FE-7kgZrD-pgzhyD-pgykqe-pw2ag5-pw2a15-py2KfS-ubtxD6-dm2tQh-dm2gga-djzYqt-8Wtv4n-dm29DH-9UpVnC-dm2iDk-djzX6K-pw2FMq-pgzfmW-pxMWoa-4xt7kK-8zkpdv-dimcas-pgykZF-py3fKy-pgzPQg-py3g13-7kkUoG-pgzeJ3-pw2LFJ-py59ai-pgzfMA-pgyRND-uQSjVT-dm2r93-dm2hAK-7aoA5A-9gJMbv-dQDM7c-9WcE6B-hXXoDf-2eFCFp-4qDV7D-hLB1Fy-dQepEF-7yJVu4-dQfbMc-jzngwo">Angels/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p><strong>Vinegar</strong></p>
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<a href="https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/99259/original/image-20151022-15414-4wsvbq.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">Also good on chips.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/cjmartin/3985707835/">Chris Martin/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Peritoneal dialysis patients, who permanently have a catheter in their abdominal cavity, sometimes develop infections on the skin around the permanent catheter. If the infection is caused by the notoriously antibiotic-resistant bacterium <em>Pseudomonas aeruginosa</em>, it can be difficult to treat and lead to the loss of the catheter and the end of that type of dialysis for the patient.</p>
<p>Bathing the site with a dilute solution of vinegar <a href="http://www.hkjn-online.com/article/S1561-5413(09)60055-7/pdf">can help resolve</a> this otherwise difficult-to-treat infection. The acidity of the vinegar due to its acetic acid content is thought to be responsible for its effectiveness.</p>
<h2>Why aren’t we doing this?</h2>
<p>In order to be substituted for antibiotics, there must be evidence that the non-antibiotic agent is <em>as</em> effective as antibiotics and is safe. The evidence would come from laboaratory-based work and clinical trials, which cost money to generate. Usually this work is done by companies that patent the product, pay the costs of development and then benefit from the market monopoly the patent gives them. </p>
<p>Many non-antibiotic antimicrobial agents such as those discussed above are not products that can be patented. Thus no drug companies can make money from their use. Consequently, the work either happens very slowly or doesn’t get done at all.</p>
<p>So despite the potentially enormous health, social and economic benefits that may flow from their development and use, including the preservation of antibiotics, there is almost no commercial incentive to develop and test them and few efficient non-commercial pathways.</p>
<p>Antibiotics are a precious, rapidly waning resource that should be preserved for as long as possible. Substituting non-antibiotic agents for antibiotics, if proven safe and effective, would mean that bacteria would be less likely to develop resistance. Then if and when they are really needed, antibiotics would still work.</p><img src="https://counter.theconversation.com/content/48655/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christine Carson receives funding from federal government funding agencies and from industry to conduct research.</span></em></p>Bacteria are becoming increasingly resistant to antibiotics and we are approaching a time when there could be many bacteria resistant to all the antibiotics we have. So how do we stop over-using them?Christine Carson, Research Associate at the University of Western Australia &, Harry Perkins Institute of Medical ResearchLicensed as Creative Commons – attribution, no derivatives.