tag:theconversation.com,2011:/nz/topics/bacterial-biofilm-27932/articlesBacterial biofilm – The Conversation2024-01-29T14:53:48Ztag:theconversation.com,2011:article/2215112024-01-29T14:53:48Z2024-01-29T14:53:48ZFrom mud and vinegar to 3D printing skin, the way we treat wounds still challenges humanity<p>Whether it’s the sting of a paper cut or the trauma of battle injury, wounds are woven into the tapestry of human experience. And since ancient times, we’ve fought the enemy that lurks within them – infection. </p>
<p>The constant threat of injury on the battlefield led to the search for new ways to combat wound infection. But early surgical procedures lacked the sterile instruments available today, meaning that for many years, surgery came with the added risk of post-operative <a href="https://cha.com/wp-content/uploads/2017/11/AJIC-2012-Infection-Control-Through-the-Ages.pdf">wound infection</a>, resulting in high numbers of deaths. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601883/">Ancient practices</a>, such as using oils, mud, turpentine, or honey to treat wounds, were common around 2000BC. The Greek physician Hippocrates (460-377BC) <a href="https://www.dermatologytimes.com/view/acetic-acid-and-wound-healing">used vinegar</a> to clean wounds, followed by bandaging to keep dirt at bay.</p>
<p>While the first hospitals were <a href="https://scientificsurgery.bjs.co.uk/article/the-surgery-of-theodoric-ca-a-d-1267-translated-from-the-latin-by-eldridge-campbell-m-d-and-james-colton-m-a-volume-i-books-i-and-ii-8-38-x-5-12-in-pp-223-xi-with-coloured-front/">established</a> in Europe in the middle ages, they were dangerous and brutal places. Wound infection rates were high because of unsanitary conditions and the use of cautery, which involved pushing a burning iron into a patient’s wound until it reached the bone.</p>
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<img alt="A drawing of a pot containing a fire with several medical instruments poking out of it." src="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A receptacle for burning coal to heat cautery instruments.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/gcg933n2/images?id=jghkdnp4">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>By the 1860s, the pioneering surgeon Joseph Lister had revolutionised wound infection treatment by introducing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895849/">carbolic-acid-soaked bandages</a>. And Robert Wood Johnson, who founded Johnson & Johnson, <a href="https://wounds-uk.com/journal-articles/sterilised-gauze-and-baby-powder-robert-wood-johnson-i-and-frederick-barnett-kilmer/">produced</a> the first sterile gauze bandages by 1890. The combination of antiseptic and sterile bandage marked a turning point in the evolution of wound treatment and infection control.</p>
<p>The discovery of penicillin by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">Alexander Fleming</a> in 1928 was also a pivotal moment in the treatment of wound infections. By the 1940s, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369031/">penicillin</a> was being used to treat second world war soldiers who had wound infections that would have been deemed fatal in previous years. For less serious wounds, Lister’s approach of using a dressing and an antiseptic was still used.</p>
<p>Substances like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756674/">silver</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/12914356/">iodine</a> have also been recognised for their antimicrobial properties since the 1800s. Iodine, though effective, caused pain and skin discolouration until safer and less painful formulations were developed in 1949. <a href="https://bnf.nice.org.uk/wound-management/antimicrobial-dressings/">These formulations</a> endure in modern wound dressings.</p>
<p>For everyday cuts and scrapes, a simple cleaning with water and application of antiseptic cream is usually enough. This helps to prevent the inadvertent introduction of bacteria into the wound, minimising the risk of additional pain and swelling. </p>
<p>But while most wounds nowadays heal without issue, some become become infected. Research published in 2021 showed that <a href="https://wounds-uk.com/wp-content/uploads/sites/2/2023/02/68803cd147c4d81a02b9cc56823f19a1.pdf">3.8 million</a> people were having their wounds managed by the NHS between 2017 and 2018, up 71% from between 2012 and 2013. They included surgical wounds, leg ulcers and burns. This shows how hard it can be to care for wounds that are difficult to heal and particularly susceptible to infections.</p>
<h2>Modern-day challenges</h2>
<p>One of the biggest challenges in the modern-day treatment of wound infection is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">antibiotic resistance</a>. This happens when bacteria develop the ability to defeat the drugs designed to kill them. Resistant infections can be difficult, and sometimes impossible, to treat. </p>
<p>Many bacteria have also become resistant to the antimicrobial ingredients used in wound dressings. This is the case for <a href="https://www.sciencedirect.com/science/article/pii/S0195670104005201">silver-based</a> wound dressings, which are often used to treat chronic wound infections. This type of wound characteristically <a href="https://www.nature.com/articles/s41572-022-00377-3">fails to heal</a>, and can remain an open, infected wound for many months – or even years. As well as the devastating effect on people’s quality of life, this also places a huge financial burden on the NHS.</p>
<p>The constant fight against wound infections drives extensive research for new, safe and effective treatments. While progress is being made, a crucial hurdle lies in the <a href="https://academic.oup.com/jacamr/article/3/1/dlab027/6186407">limitations</a> of laboratory testing methods. These tests, while necessary for regulatory approval, often fail to capture the nuanced realities of wounds in the human body. </p>
<p>No two people are the same and no two wounds are the same either. This can lead to situations where treatments shine in the lab but ultimately prove ineffective in real patients.</p>
<h2>Creating wound models</h2>
<p>In response to this, scientists are tackling the limitations of lab tests by creating more realistic synthetic wound models. Some are even <a href="https://pubmed.ncbi.nlm.nih.gov/30172300/">3D printing</a> human skin (using leftovers from surgical procedures), or animal skin, complete with artificial body fluids, such as pus. The aim is to create a model environment that mimics real wounds more accurately. </p>
<p>Recently, my own <a href="https://pubmed.ncbi.nlm.nih.gov/36678466/">research group</a> has made strides in developing lab models that act like real chronic wounds when treated with antimicrobial dressings. While not perfect, our models are a step in the right direction, contributing to the development of formulations with promising potential for treating wound infections in the future.</p>
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Read more:
<a href="https://theconversation.com/we-built-a-human-skin-printer-from-lego-and-we-want-every-lab-to-use-our-blueprint-203170">We built a human-skin printer from Lego and we want every lab to use our blueprint</a>
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<p>As we navigate the complexities of wound care, the quest for new, effective and safe treatments continues, driven by the efforts of scientists worldwide. We are working towards a future where the management of difficult-to-heal wounds and infections improves, enhancing both individual wellbeing and the efficiency of health systems.</p><img src="https://counter.theconversation.com/content/221511/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Maddocks does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Keeping wounds clean and infection free has challenged people for thousands of years.Sarah Maddocks, Lecturer in Microbiology, Cardiff Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2002262023-04-11T12:04:46Z2023-04-11T12:04:46ZLooming behind antibiotic resistance is another bacterial threat – antibiotic tolerance<figure><img src="https://images.theconversation.com/files/519955/original/file-20230407-28-ddggzn.jpg?ixlib=rb-1.1.0&rect=0%2C3%2C2309%2C1292&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tolerant bacteria are dormant until an antibiotic threat has passed, then reemerge to conduct business as usual.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pseudomonas-aeruginosa-bacterium-illustration-royalty-free-image/1201441647">Christoph Burgstedt/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Have you ever had a nasty infection that just won’t seem to go away? Or a runny nose that keeps coming back? You may have been dealing with a bacterium that is tolerant of, though not yet resistant to, antibiotics. </p>
<p>Antibiotic resistance is a huge problem, contributing to <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">nearly 1.27 million deaths worldwide in 2019</a>. But antibiotic tolerance is a covert threat that researchers have only recently begun to explore. </p>
<p><a href="https://doi.org/10.1371/journal.ppat.1008892">Antibiotic tolerance</a> happens when a bacterium manages to survive for a long time after being exposed to an antibiotic. While <a href="https://doi.org/10.1128/microbiolspec.VMBF-0016-2015">antibiotic-resistant</a> bacteria flourish even in the presence of an antibiotic, tolerant bacteria often exist in a dormant state, neither growing nor dying but putting up with the antibiotic until they can “reawaken” once the stress is gone. Tolerance has been <a href="https://www.doi.org/10.1126/science.aaj2191">linked to the spread of antibiotic resistance</a>.</p>
<p>I am a <a href="https://doerr.wicmb.cornell.edu/current-lab-members/">microbiologist</a> who studies antibiotic tolerance, and I seek to uncover what triggers tolerant bacteria to enter a protective dormant slumber. By understanding why bacteria have the ability to become tolerant, researchers hope to develop ways to avoid the spread of this ability. The exact mechanism that sets tolerance apart from resistance has been unclear. But one possible answer may reside in a process that has been overlooked for decades: how bacteria <a href="https://doi.org/10.3389/fmicb.2020.577564">create their energy</a>.</p>
<h2>Cholera and antibiotic tolerance</h2>
<p>Many antibiotics are designed to <a href="https://doi.org/10.1039/C6MD00585C">break through the bacteria’s outer defenses</a> like a cannonball through a stone fortress. Resistant bacteria are immune to the cannonball because they can either destroy it before it damages their outer wall or change their own walls to be able to withstand the impact. </p>
<p>Tolerant bacteria can remove their wall entirely and avoid damage altogether. No wall, no target for the cannonball to smash. If the threat goes away before too long, the bacterium can rebuild its wall to protect it from other environmental dangers and resume normal functions. However, it is still unknown how bacteria know the antibiotic threat is gone, and what exactly triggers their reawakening. </p>
<p>My colleagues and I at the <a href="https://doerr.wicmb.cornell.edu/">Dörr Lab at Cornell University</a> are trying to understand processes of activation and reawakening in the tolerant bacteria responsible for cholera, <em>Vibrio cholerae</em>. <em>Vibrio</em> is <a href="https://doi.org/10.3389/fitd.2021.691604">rapidly evolving resistance</a> against various types of antibiotics, and doctors are concerned. As of 2010, <em>Vibrio</em> is already <a href="https://doi.org/10.1016/j.vaccine.2019.06.031">resistant to 36 different antibiotics</a>, and this number is expected to continue rising.</p>
<p>To study how <em>Vibrio</em> develops resistance, we chose a strain that is tolerant to a class of antibiotics <a href="https://doi.org/10.3389/fpubh.2016.00231">called beta-lactams</a>. Beta-lactams are the cannonball sent to destroy the bacteria’s fortress, and <em>Vibrio</em> adapts by activating two genes that temporarily remove its cell wall. I witnessed this phenomenon using a microscope. After removing its cell wall, the bacteria activate even more genes that morph it into fragile globs that can survive the effects of the antibiotic. Once the antibiotic is removed or degraded, <em>Vibrio</em> returns to its normal rod shape and continues to grow. </p>
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<figcaption><span class="caption">Normally rod-shaped <em>Vibrio cholerae</em> remove their cell walls and turn into globs in the presence of penicillin, enabling them to survive longer.</span></figcaption>
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<figcaption><span class="caption"><em>Vibrio cholerae</em> revert back to their rod-shaped structure once the antibiotic threat is removed.</span></figcaption>
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<p>In people, this process of tolerance is seen when a doctor prescribes an antibiotic, typically doxycycline, to a patient infected with cholera. The antibiotic temporarily seems to stop the infection. But then the symptoms start back up again because the antibiotics never fully cleared the bacteria in the first place.</p>
<p>The ability to revert back to normal and grow after the antibiotic is gone is the key to tolerant survival. Exposing <em>Vibrio</em> to an antibiotic for a long enough time would eventually kill it. But a standard course of antibiotics often isn’t long enough to get rid of all the bacteria even in their fragile state.</p>
<p>However, taking a medicine for a prolonged period can harm healthy bacteria and cells, causing further discomfort and illness. Additionally, <a href="https://doi.org/10.3389/fcimb.2020.572912">misuse and extended exposure</a> to antibiotics can increase the chances of other bacteria residing in the body becoming resistant.</p>
<h2>Other bacteria developing tolerance</h2>
<p><em>Vibrio</em> isn’t the only species to exhibit tolerance. In fact, researchers have recently identified many infectious bacteria that have developed tolerance. A bacteria family called <a href="https://doi.org/10.1371/journal.pbio.1001928">Enterobacteriaceae</a>, which include major food-borne disease pathogens <a href="https://doi.org/10.1371/journal.pbio.1001928"><em>Salmonella</em></a>, <a href="https://doi.org/10.1128/AAC.01282-08"><em>Shigella</em></a> and <a href="https://doi.org/10.1038/s41598-021-85509-7"><em>E. coli</em></a>, are just a few of the many types of bacteria that are capable of antibiotic tolerance.</p>
<p>As every bacterium is unique, the way one develops tolerance seems to be as well. Some bacteria, like <em>Vibrio</em>, <a href="https://doi.org/10.1128/AAC.00756-19">erase their cell walls</a>. Others can <a href="https://doi.org/10.1038/nchembio.1754">alter their energy sources, increase their ability to move or simply pump out</a> the antibiotic.</p>
<p>I recently found that a <a href="https://doi.org/10.1128/jb.00476-22">bacterium’s metabolism</a>, or the way it breaks down “food” to make energy, may play a significant role in its ability to become tolerant. Different structures within a bacterium, including its outer wall, are made of specific building blocks like proteins. Stopping the bacterium’s ability to craft these pieces weakens its wall, making it more likely to take damage from the outside environment before it can take the wall down.</p>
<h2>Tolerance and resistance are connected</h2>
<p>Although there has been considerable research on how bacteria develop tolerance, a key piece of the puzzle that has been neglected is how tolerance leads to resistance.</p>
<p>In 2016, researchers discovered how to <a href="https://doi.org/10.1038/nmicrobiol.2016.20">make bacteria tolerant in the laboratory</a>. After repeated exposure to different antibiotics, <em>E. coli</em> cells were able to adapt and survive. DNA, the genetic material containing instructions for cell function, is a fragile molecule. When DNA is damaged rapidly by stress, such as antibiotic exposure, the cell’s repair mechanisms tend to mess up and cause mutations that can create resistance and tolerance. Because <em>E. coli</em> is similar to many different types of bacteria, these researchers’ findings revealed that, ironically, essentially any bacteria can develop tolerance if pushed to their limits by the antibiotics meant to kill them. </p>
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<figcaption><span class="caption">Bacteria form large communities in biofilms.</span></figcaption>
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<p>Another recent key discovery was that the longer bacteria remain tolerant, the more likely they are to <a href="https://doi.org/10.1073/pnas.2209043119">develop mutations leading to resistance</a>. Tolerance allows bacteria to develop a resistance mutation that reduces their chances of being killed during antibiotic treatment. This is especially relevant to bacterial communities often seen in <a href="https://doi.org/10.2147/IDR.S379502">biofilms that tend to coat high-touch surfaces in hospitals</a>. Biofilms are slimy layers of bacteria that ooze a protective jelly that makes antibiotic treatment difficult and DNA sharing between microbes easy. They can induce bacteria to evolve resistance. These conditions are thought to mimic what could be happening during antibiotic-treated infections, in which many bacteria are living next to one another and sharing DNA. </p>
<p>Researchers are calling for more research into antibiotic tolerance with the hope that it will lead to <a href="https://doi.org/10.1128/mBio.02095-19">more robust treatments</a> in both infectious diseases and cancers. And there is reason to be hopeful. In one promising development, a mouse study found that <a href="https://doi.org/10.1126/science.1211037">decreasing tolerance also reduced resistance</a>. </p>
<p>Meanwhile, there are steps everyone can take to aid in the battle against antibiotic tolerance and resistance. You can do this by <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">taking an antibiotic exactly as prescribed</a> by a doctor and finishing the entire bottle. Brief, inconsistent exposure to a medicine primes bacteria to become tolerant and eventually resistant. Smarter use of antibiotics by everyone can stop the evolution of tolerant bacteria.</p><img src="https://counter.theconversation.com/content/200226/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Keller receives funding from the National Science Foundation Graduate Research Fellowship Program and the National Institutes of Health (NSF GRFP #DGE-1650441 and NIH R01-AI143704)</span></em></p>Antibiotic resistance has contributed to millions of deaths worldwide. Research suggests that any bacteria can develop antibiotic tolerance, and possibly resistance, when pushed to their limits.Megan Keller, Ph.D. Candidate in Microbiology, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1410532020-07-23T19:52:25Z2020-07-23T19:52:25ZAs if space wasn’t dangerous enough, bacteria become more deadly in microgravity<figure><img src="https://images.theconversation.com/files/347007/original/file-20200713-42-1k8juza.jpg?ixlib=rb-1.1.0&rect=162%2C62%2C5013%2C2848&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>China <a href="https://spaceflightnow.com/2020/07/21/china-moves-massive-rocket-into-place-for-ambitious-mars-shot/">has launched</a> its Tianwen-1 mission to Mars. A rocket holding an orbiter, lander and rover took flight from the country’s Hainan province yesterday, with hopes to deploy the rover on Mars’s surface by early next year.</p>
<p>Similarly, the launch of the <a href="https://www.space.com/uae-hope-emirates-mars-mission-launch-webcast.html">Emirates Mars Mission</a> on Sunday marked the Arab world’s foray into interplanetary space travel. And on July 30, we expect to see NASA’s Mars Perseverance rover <a href="https://www.space.com/mars-rover-perseverance-launch-delay-july-30-2020.html">finally</a> take off from Florida.</p>
<p>For many nations and their people, space is becoming the ultimate frontier. But although we’re gaining the ability to travel smarter and faster into space, much remains unknown about its effects on biological substances, including us. </p>
<p>While the possibilities of space exploration seem endless, so are its dangers. And one particular danger comes from the smallest life forms on Earth: bacteria. </p>
<p>Bacteria live <a href="https://kids.frontiersin.org/article/10.3389/frym.2017.00035">within us and all around us</a>. So whether we like it or not, these microscopic organisms tag along wherever we go – including into space. Just as space’s unique environment has an impact on us, so too does it impact bacteria.</p>
<h2>We don’t yet know the gravity of the problem</h2>
<p>All life on Earth evolved with gravity as an ever-present force. Thus, Earth’s life has not adapted to spend time in space. When gravity is removed or greatly reduced, processes influenced by gravity behave differently as well. </p>
<p>In space, where there is minimal gravity, sedimentation (when solids in a liquid settle to the bottom), convection (the transfer of heat energy) and buoyancy (the force that makes certain objects float) <a href="https://iss.jaxa.jp/en/kiboexp/seu/categories/microgravity/index.html">are minimised</a>.</p>
<p>Similarly, forces such as liquid <a href="https://www.usgs.gov/special-topic/water-science-school/science/surface-tension-and-water?qt-science_center_objects=0#qt-science_center_objects">surface tension</a> and capillary forces (when a liquid flows to fill a narrow space) <a href="https://iopscience.iop.org/article/10.1088/0143-0807/35/5/055010">become more intense</a>. </p>
<p>It’s not yet fully understood how such changes impact lifeforms.</p>
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<a href="https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/347008/original/file-20200713-22-1a7jbvj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">NASA’s Perseverance Mars rover will be launched later this month. Among other tasks, it will seek out past microscopic life and collect samples of Martian rock and regolith (broken rock and dust) to later be returned to Earth.</span>
<span class="attribution"><span class="source">NASA/Cover Images</span></span>
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<h2>How bacteria become more deadly in space</h2>
<p>Worryingly, research from space flight missions has shown bacteria become more deadly and resilient when exposed to microgravity (when only tiny gravitational forces are present).</p>
<p>In space, bacteria seem to become <a href="https://link.springer.com/article/10.1007%2Fs00248-013-0193-4">more resistant to antibiotics</a> and <a href="https://www.nature.com/articles/s41526-019-0091-2">more lethal</a>. They also stay this way for a short time after <a href="https://www.npr.org/templates/story/story.php?storyId=14653292">returning to Earth</a>, compared with bacteria that never left Earth. </p>
<p>Adding to that, bacteria also seem to <a href="https://www.nature.com/articles/s41526-017-0020-1">mutate quicker</a> in space. However, these mutations are predominately for the bacteria to <a href="https://msystems.asm.org/content/4/1/e00281-18">adapt to the new environment</a> – not to become super deadly. </p>
<p>More research is needed to examine whether such adaptations do, in fact, allow the bacteria to cause more disease. </p>
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<a href="https://theconversation.com/bacteria-found-to-thrive-better-in-space-than-on-earth-56740">Bacteria found to thrive better in space than on Earth</a>
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<h2>Bacterial team work is bad news for space stations</h2>
<p>Research has shown space’s microgravity promotes <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062437">biofilm formation of bacteria</a>.</p>
<p>Biofilms are densely-packed cell colonies that produce a matrix of polymeric substances allowing bacteria to stick to each other, and to stationary surfaces. </p>
<p>Biofilms increase bacteria’s resistance to antibiotics, promote their survival and improve their ability to cause infection. We have seen biofilms <a href="https://pubmed.ncbi.nlm.nih.gov/31719234/">grow and attach to equipment</a> on space stations, causing it to biodegrade. </p>
<p>For example, biofilms have affected the <a href="https://history.nasa.gov/SP-4225/mir/mir.htm">Mir</a> space station’s navigation window, air conditioning, oxygen electrolysis block, water recycling unit and thermal control system. The prolonged exposure of such equipment to biofilms can lead to malfunction, which can have devastating effects.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/347010/original/file-20200713-42-pl734s.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">Microorganisms that form biofilms include bacteria, fungi and protists.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Another affect of microgravity on bacteria involves <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581483/">their structural distortion</a>. Certain bacteria have shown reductions in cell size and increases in cell numbers when grown in microgravity. </p>
<p>In the case of the former, bacterial cells with smaller surface area have fewer molecule-cell interactions, and this reduces the effectiveness of antibiotics against them.</p>
<p>Moreover, the absence of effects produced by gravity, such as sedimentation and buoyancy, could alter the way bacteria take in nutrients or drugs intended to attack them. This could result in the increased drug resistance and infectiousness of bacteria in space.</p>
<p>All of this has serious implications, especially when it comes to long-haul space flights where gravity would not be present. Experiencing a bacterial infection that cannot be treated in these circumstances would be catastrophic.</p>
<h2>The benefits of performing research in space</h2>
<p>On the other hand, the effects of space also result in a unique environment that can be positive for life on Earth. </p>
<p>For example, <a href="https://courses.lumenlearning.com/introchem/chapter/molecular-crystals/">molecular crystals</a> in space’s microgravity grow much <a href="https://upward.issnationallab.org/microgravity-molecular-crystal-growth/">larger and more symmetrically</a> than on Earth. Having more uniform crystals allows the formulation of <a href="https://www.nasa.gov/mission_pages/station/research/news/lmm_biophysics">more effective drugs</a> and treatments to combat various diseases including cancers and Parkinson’s disease. </p>
<p>Also, the crystallisation of molecules helps determine <a href="https://theconversation.com/explainer-what-is-x-ray-crystallography-22143">their precise structures</a>. Many molecules that cannot be crystallised on Earth can be in space. </p>
<p>So, the structure of such molecules <a href="https://www.issnationallab.org/blog/designing-better-drugs-piecing-together-protein-function-through-structure/">could be determined</a> with the help of space research. This, too, would aid the development of higher quality drugs.</p>
<p>Optical fibre cables can also be made to a <a href="https://www.nasa.gov/mission_pages/station/research/news/b4h-3rd/eds-mis-building-better-optical-fiber/#:%7E:text=Made%20in%20Space%E2%80%94Building%20a%20Better%20Optical%20Fiber,the%20AMF%20on%20the%20ISS.&text=Combined%20zirconium%2C%20barium%2C%20lanthanum%2C,and%20degrade%20an%20optical%20signal.">much better standard</a> in space, due to the optimal formation of crystals. This greatly increases data transmission capacity, making networking and telecommunications faster. </p>
<p>As humans spend more time in space, an environment riddled with known and unknown dangers, further research will help us thoroughly examine the risks – and the potential benefits – of space’s unique environment.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/with-or-without-you-the-role-of-the-moon-on-life-11501">With or without you: the role of the moon on life</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/141053/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Vikrant Minhas is a co-founder of the space research company ResearchSat</span></em></p>Bacteria can become more deadly and antibiotic-resilient in space. And while more research is needed to figure out how severe the risks are, they could be catastrophic.Vikrant Minhas, PhD candidate, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1026982018-10-16T10:40:01Z2018-10-16T10:40:01ZHow scientists are fighting infection-causing biofilms<figure><img src="https://images.theconversation.com/files/236757/original/file-20180917-158243-7f66pd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An artist depiction of a biofilm harboring antibiotic-resistant rod-shaped and spherical bacteria.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/360degree-spherical-panorama-view-inside-biofilm-449656513?src=EossfLJ3eo9oOQb0QrDj7A-1-9">Kateryna Kon/Shutterstock.com</a></span></figcaption></figure><p>The surfaces people interact with every day may seem rather mundane, but at the molecular scale, there is more activity than meets the eye. </p>
<p>Every surface we touch has its own unique chemical properties. It’s because of these properties that some materials stick to surfaces, while others slide off. For a person, a sticky surface may be a minor annoyance, but for a bacterial cell, surface attachment can be a matter of life and death. Bacteria have evolved their own surfaces to be sticky, like Velcro. </p>
<p>When bacteria colonize a surface, they create a community called a biofilm, which can be a source of infection on medical devices or implants. Growing concerns over these infections has led a number of researchers to develop materials to block these sometimes dangerous films.</p>
<p>As biophysical chemists, <a href="https://www.chemistry.msstate.edu/people/faculty/nicholas-fitzkee/">my research group</a> and I are trying to understand the molecular forces that allow biological molecules – like those on bacteria – to attach to surfaces during the earliest phases of biofilm formation. By understanding this early attachment stage, we can reduce the risks that a biofilm will form on implanted medical devices and pose a threat to humans.</p>
<h2>Bacterial colonies</h2>
<p>Biofilms are densely packed <a href="https://theconversation.com/unlocking-the-secrets-of-bacterial-biofilms-to-use-against-them-59148">communities</a> of bacteria or other microorganisms living on a surface. Like a city, growing within a biofilm has certain advantages. For example, it provides structural support, like the floors of a high rise, and microbes can share nutrients. Compared to free-floating bacteria, bacteria in a biofilm are shielded, allowing them to evade our immune system and resist antibiotics. </p>
<p>When biofilms form on medical devices or implants, they can serve as a persistent source of hard-to-treat <a href="http://doi.org/10.1126/science.284.5418.1318">infections</a>. These cost not only <a href="https://dx.doi.org/10.1586%2Ferp.09.53">billions of dollars</a> to treat, but claim <a href="https://doi.org/10.1177%2F003335490712200205">thousands of lives</a> each year in the U.S. alone.</p>
<p>Scientists are trying to understand how biofilms form and how to prevent them. Molecular biologists are working out how bacterial DNA encodes for the <a href="https://iai.asm.org/content/67/10/5427">machinery</a> that allows cells to attach to surfaces and one another. Microbiologists and medicinal chemists are looking for <a href="https://theconversation.com/triclosan-often-maligned-may-have-a-good-side-treating-cystic-fibrosis-infections-98063">drugs</a> that can penetrate and disrupt biofilms. And biophysical chemists like myself are trying to sleuth out the molecular interactions that make these biofilms challenging to prevent.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/236762/original/file-20180917-158225-tjo9f3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"><em>Staphylococcus aureus</em> biofilm on the surface of a catheter.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Staphylococcus_aureus_biofilm_01.jpg">Rodney M. Donlan, Janice Carr /CDC</a></span>
</figcaption>
</figure>
<h2>Surface complexity</h2>
<p><em>Staphylococcus aureus</em> and <em>S. epidermidis</em> are two bacterial species that normally pose little problem for our bodies. However, when a staphylococcal biofilm forms on the surface of a medical implant like an artificial hip, these cells can cause disease. Staphylococcal biofilms are held together by sugars or <a href="https://iai.asm.org/content/73/10/6868">polysaccharides</a>, <a href="https://doi.org/10.1046/j.1365-2958.1997.4101774.x">proteins</a> and <a href="https://doi.org/10.5301/ijao.5000051">nucleic acids</a>, the molecular building blocks of all living organisms. These components enable the bacterial cells to stick not only to <a href="https://doi.org/10.1073/pnas.1208134110">each other</a>, but also to natural and implanted surfaces in the body – like a heart valve.</p>
<p>The surfaces of medical devices are complex, especially once they have been exposed to the body. <a href="https://doi.org/10.1093/infdis/158.4.693">Human blood proteins</a> rapidly coat the surface of medical implants, altering the character as both the patient and the device age. When a bacterial cell attaches to one of these surfaces, the components of the cell interact with the surface of the medical implant, forming a complex network of interactions. In our research, we are investigating the bacterial surface proteins that are involved in surface attachment. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=438&fit=crop&dpr=1 600w, https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=438&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=438&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=551&fit=crop&dpr=1 754w, https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=551&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/236759/original/file-20180917-158216-thegt0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=551&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Biofilms pervade all elements of our lives. For example the plaque that forms on your teeth is a biofilm that shelters bacteria. If the plaque isn’t removed, the tissue around the tooth will become inflamed.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/dental-plaque-inflammation-healthy-tooth-on-324725045?src=EossfLJ3eo9oOQb0QrDj7A-1-60">Nita_Nita/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Studying these interactions is challenging. Typically, chemistry experiments are carried out in solution, but biofilm experiments must be done on a surface. Detecting the molecules at the surface is a challenge. That’s because there are fewer of those molecules compared to the overall volume of the material, just as the skin of the tomato is tiny fraction of the mass of the entire tomato.</p>
<h2>Introducing the nanoscale</h2>
<p>To overcome this limitation, we are investigating how proteins present on the bacterial surface interact with <a href="https://doi.org/10.1038/nmat2442">nanoparticle surfaces</a>. Specifically, we are using nanoparticles designed to mimic the surface of medical devices, and we are targeting proteins involved in staphylococcal infections, a major source of hospital related illness. </p>
<p>Nanoparticles have a diameter much smaller than a bacterial cell. But while a typical cell would dwarf a nanoparticle, the nanoparticle is still much bigger than the molecules on the surface of a cell. By using many nanoparticles it is easier to observe how the bacterium and particle interact and observe the bacterial molecules involved in biofilm formation. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/235705/original/file-20180910-123113-1h4kzh8.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">Randika Perera places a nanoparticle sample into an NMR spectrometer, one of the instruments used to study protein-surface interactions.</span>
<span class="attribution"><span class="source">Sarah Tewolde, MSU Office of Public Affairs</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Specifically, we are trying to understand the structure and orientation of proteins on different types of surfaces. While we are not the first or the only group to be interested in this topic, our work has begun to reveal the <a href="http://doi.org/10.1021/jp411543y">molecular details</a> of how proteins interact with nanoparticle surfaces. </p>
<p>We can probe how tightly the bacteria are clinging to a surface – and we can examine how protein molecules <a href="https://doi.org/10.1021/acs.jpcc.6b08469">compete</a> for the same surface. For example, given a collection of bacterial proteins, which of these will ultimately attach to the surface of a medical implant?</p>
<p>As we discover the answers to these questions we will be able to identify the important elements involved in early biofilm formation. This will be useful for scientists attempting to inhibit those interactions <a href="https://doi.org/10.1046/j.1365-2958.2002.02827.x">therapeutically</a>, or those seeking to design new <a href="https://doi.org/10.1016/j.biomaterials.2013.07.089">biofilm-resistant surfaces</a>.</p><img src="https://counter.theconversation.com/content/102698/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicholas Fitzkee receives funding from the National Institutes of Health and the National Science Foundation. </span></em></p>Smooth surfaces often provide nooks and crannies for bacteria to hold onto and create a colony. New research with nanoparticles is revealing the secrets of surfaces that prevent bacterial attachment.Nicholas Fitzkee, Associate Professor of Chemistry, Mississippi State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/980632018-07-11T11:15:22Z2018-07-11T11:15:22ZTriclosan, often maligned, may have a good side — treating cystic fibrosis infections<figure><img src="https://images.theconversation.com/files/226366/original/file-20180705-122274-zwsz42.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotic-resistant bacteria inside a biofilm.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibiotic-resistant-bacteria-inside-biofilm-3d-733165693?src=S-PIB9t8jY1oDGnWwDSB3w-1-0">Kateryna Kon/Shutterstock.com</a></span></figcaption></figure><p>Maybe you’ve had the experience of wading in a stream and struggling to keep your balance on the slick rocks, or forgetting to brush your teeth in the morning and feeling a slimy coating in your mouth. These are examples of <a href="http://www.biofilm.montana.edu/biofilm-basics/index.html">bacterial biofilms</a> that are found anywhere a surface is exposed to bacteria in a moist environment.</p>
<p>Besides leading to falls in streams or creating unhealthy teeth, <a href="https://theconversation.com/unlocking-the-secrets-of-bacterial-biofilms-to-use-against-them-59148">biofilms</a> can cause large problems when they infect people. Biofilms, multicellular communities of bacteria that can grow on a surface encased in their own self-produced matrix of slime, <a href="https://www.sciencedirect.com/science/article/pii/B9780128002629000019?via%3Dihub">can block immune cells</a> from engulfing and killing the bacteria or prevent antibodies from binding to their surface. </p>
<p>On top of this, bacteria in a biofilm <a href="http://www.jbc.org/content/291/24/12565.long">resist being killed</a> by antibiotics due to the sticky nature of the matrix and activation of inherent resistant mechanisms, such as slow-growing cells or the ability to pump antibiotics out of the cell. </p>
<p>Biofilms are one of the primary growth modes of bacteria, but all antibiotics currently used clinically were developed against <a href="http://www.mdpi.com/1420-3049/20/4/5286/htm">free-swimming planktonic bacteria</a>. This is why they do not work well against biofilms. </p>
<p><a href="https://msu.edu/%7Ewatersc3/">My laboratory</a> studies how and why bacteria make biofilms, and we develop new therapeutics to target them. Because <a href="https://www.nature.com/articles/s41579-018-0019-y">antibiotic resistance</a> is the most problematic aspect of biofilms during infections, we set out to identify novel molecules that could enhance antibiotic activity against these communities. </p>
<p>We discovered that an antimicrobial that has recently obtained a bad reputation for overuse in many household products could be the secret sauce to kill biofilms.</p>
<h2>The hunt for antibiotic superchargers</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=472&fit=crop&dpr=1 600w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=472&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=472&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=593&fit=crop&dpr=1 754w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=593&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=593&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dr. Alessandra Agostinho Hunt measures biofilm formation of <em>Psuedomonas aerugionsa</em> by pipetting in the purple dye crystal violet to stain the microbial structure.</span>
<span class="attribution"><span class="source">Derrick Turner/Michigan State University</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>To find such compounds, we developed an <a href="https://www.medicinenet.com/script/main/art.asp?articlekey=8412">assay</a> to grow plates of 384 tiny <a href="http://aac.asm.org/content/62/6/e00146-18.long">biofilms</a> of the bacterium <a href="https://www.tandfonline.com/doi/abs/10.1517/14728220903454988?journalCode=iett20"><em>Pseudomonas aeruginosa</em></a>. We did this to screen for molecules that enhance killing by the antibiotic <a href="https://www.rxlist.com/consumer_tobramycin_nebcin/drugs-condition.htm">tobramycin</a>. We chose this bacterium and this antibiotic as our test subjects because they are commonly associated with <a href="https://www.cff.org/Life-With-CF/Daily-Life/Germs-and-Staying-Healthy/What-Are-Germs/Pseudomonas/">cystic fibrosis lung infections</a> and treatment.</p>
<p>People with cystic fibrosis (CF) are at particular risk from <a href="https://www.ncbi.nlm.nih.gov/pubmed/19374653">biofilm-based infections</a>. These infections often become chronic in the lungs of cystic fibrosis patients and are often never cleared, even with aggressive antibiotic therapy.</p>
<p>After we screened 6,080 small molecules in the presence of tobramycin, we found multiple compounds that showed the antibiotic enhancement activity we were searching for. Of particular interest was the antimicrobial <a href="https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm205999.htm">triclosan</a> because it has been widely used in household products like toothpaste, soaps and hand sanitizers for decades, indicating that it had potential to be safely used in CF patients. <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jat.1660">Triclosan</a> has also garnered a <a href="https://theconversation.com/why-you-should-dispense-with-antibacterial-soaps-65297">bad reputation</a> due to its overuse, and states like Minnesota have banned it from these products. The <a href="https://theconversation.com/why-you-should-dispense-with-antibacterial-soaps-65297">Food and Drug Administration banned</a> its use from hand soaps in September 2016. This ruling was not based on safety concerns, but rather because the companies that made these products did not demonstrate higher microbial killing when triclosan was added, compared to the base products alone.</p>
<p>Another fact that piqued our interest is that <em>P. aeruginosa</em> is resistant to triclosan. Indeed, treatment with either tobramycin or triclosan alone had very little activity against <em>P. aeruginosa</em> biofilms, but we found that the combination was 100 times more active, killing over 99 percent of the bacteria.</p>
<p>We further studied this combination and found that it worked against <em>P. aeruginosa</em> and other bacterial species that had been isolated from the lungs of CF patients. The combination also significantly enhanced the speed of killing so that at two hours of treatment, virtually all of the biofilm is eradicated. </p>
<p>Our efforts are now focused on pre-clinical development of the <a href="https://www.tobipodhaler.com/index.jsp?usertrack.filter_applied=true&NovaId=2935377102246013691">tobramycin-triclosan combination</a>. For CF, we envision patients will inhale these antimicrobials as a combination therapy, but it could also be used for other applications such as diabetic non-healing wounds. </p>
<p>Although questions about the safety of triclosan have emerged in the mainstream media, there are actually dozens of studies, including in humans, <a href="https://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_166.pdf">concluding that it is well tolerated</a>, summarized in this extensive EU report from 2009. My laboratory completely agrees that triclosan has been significantly overused, and it should be reserved to combat life-threatening infections.</p>
<p>The next steps for development are to initiate safety, efficacy and pharmacological studies. And thus far, our own studies indicate that <a href="http://aac.asm.org/content/early/2018/04/10/AAC.00146-18.full.pdf+html">triclosan is well tolerated</a> when directly administered to the lungs. We hope that in the near future we will have enough data to initiate clinical trials with the FDA to test the activity of this combination in people afflicted with biofilm-based infections.</p>
<p>We think our approach of enhancing biofilm activity with the addition of novel compounds will increase the usefulness of currently used antibiotics. Learning about how these compounds work will also shed light on how bacterial biofilms resist antibiotic therapy.</p><img src="https://counter.theconversation.com/content/98063/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Waters receives funding from the NIH, NSF, Michigan State University, and Hunt for a Cure Foundation to support this research.</span></em></p>Triclosan, an ingredient in soap and many household cleansers, has gained a bad reputation. A recent study looking for a way to boost an antibiotic, however, found that tricloscan did a great job.Chris Waters, Associate Professor of Microbiology, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/642842016-10-19T01:02:27Z2016-10-19T01:02:27ZHow many genes does it take to make a person?<figure><img src="https://images.theconversation.com/files/142060/original/image-20161017-12463-1xoaj7s.jpg?ixlib=rb-1.1.0&rect=1161%2C0%2C5604%2C4000&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Do we contain the most elaborate set of instructions?</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-481861843.html">Genome image via www.shutterstock.com.</a></span></figcaption></figure><p>We humans like to think of ourselves as on the top of the heap compared to all the other living things on our planet. Life has evolved over three billion years from simple one-celled creatures through to multicellular plants and animals coming in all shapes and sizes and abilities. In addition to growing ecological complexity, over the history of life we’ve also seen the evolution of intelligence, complex societies and technological invention, until we arrive today at people flying around the world at 35,000 feet discussing the in-flight movie.</p>
<p>It’s natural to think of the history of life as progressing <a href="https://www.wired.com/2014/08/where-animals-come-from/">from the simple to the complex</a>, and to expect this to be reflected in increasing gene numbers. We fancy ourselves leading the way with our superior intellect and global domination; the expectation was that since we’re the most complex creature, we’d have the most elaborate set of genes.</p>
<p>This presumption seems logical, but the more researchers figure out about various genomes, the more flawed it seems. About a half-century ago the estimated number of human genes was in the millions. <a href="http://doi.org/10.1186/gb-2010-11-5-206">Today we’re down to about 20,000</a>. We now know, for example, that bananas, with their <a href="http://doi.org/10.1038/nature11241">30,000 genes</a>, have 50 percent more genes than we do. </p>
<p>As researchers devise new ways to count not just the genes an organism has, but also the ones it has that are superfluous, there’s a clear convergence between the number of genes in what we’ve always thought of as the simplest lifeforms – viruses – and the most complex – us. It’s time to rethink the question of how the complexity of an organism is reflected in its genome.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=325&fit=crop&dpr=1 600w, https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=325&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=325&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=408&fit=crop&dpr=1 754w, https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=408&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/136179/original/image-20160901-30772-1ngr36h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=408&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 converging estimated number of genes in a person versus a giant virus. Human line shows average estimate with dashed line representing estimated number of genes needed. Numbers shown for viruses are for MS2 (1976), HIV (1985), giant viruses from 2004 and average T4 number in the 1990s.</span>
<span class="attribution"><span class="source">Sean Nee</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Counting up the genes</h2>
<p>We can think of all our genes together as the recipes in a cookbook for us. They’re written in the letters of the bases of DNA – abbreviated as ACGT. The genes provide instructions on how and when to assemble the proteins that you’re made of and that carry out all the functions of life within your body. A <a href="http://doi.org/10.1093/nar/gki615">typical</a> gene requires about 1000 letters. Together with the environment and experience, genes are responsible for what and who we are – so it’s interesting to know how many genes add up to a whole organism. </p>
<p>When we’re talking about numbers of genes, we can display the actual count for viruses, but only the estimates for human beings for an important reason. One <a href="http://doi.org/10.1038/nrg3117">challenge</a> counting genes in <a href="https://youtu.be/bo0QHAS-x8A">eukaryotes</a> – which include us, bananas and yeast like Candida – is that our genes are not lined up like ducks in a row. </p>
<p>Our genetic recipes are arranged as if the cookbook’s pages have all been ripped out and mixed up with three billion other letters, about <a href="http://book.bionumbers.org/how-many-genes-are-in-a-genome/">50 percent</a> of which actually describe inactivated, dead viruses. So in eukaryotes it’s hard to count up the genes that have vital functions and separate them from what’s extraneous.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=620&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=620&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=620&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=779&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=779&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142062/original/image-20161017-12443-15i77k1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=779&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Megavirus has over a thousand genes, Pandoravirus has even more.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Megavirus.jpg">Chantal Abergel</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In contrast, counting genes in viruses – and bacteria, which can have <a href="http://doi.org/10.1093/gbe/evs117">10,000</a> genes – is relatively easy. This is because the raw material of genes – nucleic acids – is relatively expensive for tiny creatures, so there is strong selection to delete unnecessary sequences. In fact, the real challenge for viruses is discovering them in the first place. It is startling that all <a href="http://doi.org/10.1098/rsos.160235">major virus discoveries</a>, including HIV, have not been made by sequencing at all, but by old methods such as magnifying them visually and looking at their morphology. <a href="http://doi.org/10.5501/wjv.v4.i3.265">Continuing advances</a> in molecular technology have taught us the remarkable <a href="http://doi.org/10.1038/nrmicro1750">diversity of the virosphere</a>, but can only help us count the genes of something we already know exists.</p>
<h2>Flourishing with even fewer</h2>
<p>The number of genes we actually need for a healthy life is probably even lower than the current estimate of 20,000 in our entire genome. One author of a recent study has reasonably extrapolated that the count for essential genes for human beings <a href="http://www.qmul.ac.uk/media/news/items/smd/171926.html">may be much lower</a>. </p>
<p>These researchers looked at thousands of healthy adults, <a href="http://doi.org/10.1126/science.aac8624">looking for naturally occurring “knockouts,”</a> in which the functions of particular genes are absent. All our genes come in two copies – one from each parent. Usually, one active copy can compensate if the other is inactive, and it is difficult to find people with <em>both</em> copies inactivated because inactivated genes are naturally rare. </p>
<p>Knockout genes are fairly easy to study with lab rats, using modern genetic engineering techniques to inactivate both copies of particular genes of our choice, or even remove them altogether, and see what happens. But human studies require populations of people living in communities with 21st century medical technologies and known pedigrees suited to the genetic and statistical analyses required. <a href="https://www.genome.gov/27561444/iceland-study-provides-insights-into-disease-paves-way-for-largescale-genomic-studies/">Icelanders are one useful</a> population, and the British-Pakistani people of this study are another. </p>
<p>This research found over 700 genes which can be knocked out with no obvious health consequences. For instance, one surprising discovery was that the PRDM9 gene – which plays a crucial role in the fertility of mice – can also be knocked out in people with no ill effects.</p>
<p>Extrapolating the analysis beyond the human knockouts study <a href="http://www.independent.co.uk/news/science/human-genome-study-finds-many-genes-have-no-effect-on-human-health-a6914446.html">leads to an estimate</a> that only 3,000 human genes are actually needed to build a healthy human. This is in the same ballpark as the number of genes in “<a href="http://www.giantvirus.org/">giant viruses</a>.” <a href="http://doi.org/10.1038/nature.2013.13410">Pandoravirus</a>, recovered from 30,000-year-old Siberian ice in 2014, is the largest virus known to date and <a href="http://doi.org/10.1073/pnas.1320670111">has 2,500 genes</a>.</p>
<p>So what genes do we need? We don’t even know what a quarter of human genes actually do, and this is advanced <a href="http://doi.org/10.1186/gb-2006-7-7-r57">compared to our knowledge of other species</a>.</p>
<h2>Complexity arises from the very simple</h2>
<p>But whether the final number of human genes is 20,000 or 3,000 or something else, the point is that when it comes to understanding complexity, size really does not matter. We’ve known this for a long time in at least two contexts, and are just beginning to understand the third.</p>
<p>Alan Turing, the mathematician and <a href="http://www.slate.com/blogs/browbeat/2014/12/03/the_imitation_game_fact_vs_fiction_how_true_the_new_movie_is_to_alan_turing.html">WWII code breaker</a> established the theory of multicellular development. He studied simple mathematical models, now called “reaction-diffusion” processes, in which a small number of chemicals – just two in Turing’s model – diffuse and react with each other. With simple rules governing their reactions, these models <a href="http://www.brandeis.edu/now/2014/march/turingpnas.html">can reliably generate</a> very complex, yet coherent structures <a href="https://www.youtube.com/watch?v=-RZLO7_Lk5s&feature=youtu.be">that are easily seen</a>. So the biological structures of plants and animals do not require complex programming.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=564&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=564&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142061/original/image-20161017-12418-1y6gkfe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=564&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 simple building blocks of neurons together generate immense complexity.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/126293865@N04/14953538130">UCI Research/Ardy Rahman</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>Similarly, it is obvious that the <a href="http://theastronomist.fieldofscience.com/2011/07/cubic-millimeter-of-your-brain.html">100 trillion connections</a> in the human brain, which are what really make us who we are, cannot possibly be genetically programmed individually. The <a href="http://www.wired.com/2014/10/future-of-artificial-intelligence/">recent breakthroughs in artificial intelligence</a> are based on <a href="http://www.extremetech.com/extreme/215170-artificial-neural-networks-are-changing-the-world-what-are-they">neural networks</a>; these are computer models of the brain in which simple elements – corresponding to neurons – establish their own connections through interacting with the world. The <a href="http://www.kurzweilai.net/how-bio-inspired-deep-learning-keeps-winning-competitions">results have been spectacular</a> in applied areas such as handwriting recognition and medical diagnosis, and Google has invited the public to <a href="https://theconversation.com/leurope-de-lintelligence-artificielle-est-en-marche-63609">play games with</a> and <a href="http://www.theatlantic.com/technology/archive/2015/09/robots-hallucinate-dream/403498/">observe the dreams</a> of its AIs.</p>
<h2>Microbes go beyond basic</h2>
<p>So it’s clear that a single cell does not need to be very complicated for large numbers of them to produce very complex outcomes. Hence, it shouldn’t come as a great surprise that human gene numbers may be of the same size as those of single-celled microbes like viruses and bacteria.</p>
<p>What is coming as a surprise is the converse – that tiny microbes can have rich, complex lives. There is a growing field of study – dubbed “<a href="http://www.ncbi.nlm.nih.gov/pubmed/15639629">sociomicrobiology</a>” – that examines the extraordinarily complex social lives of microbes, which stand up in comparison with our own. <a href="http://rsos.royalsocietypublishing.org/content/3/8/160235">My own contributions</a> to these areas concern giving viruses their rightful place in this invisible soap opera.</p>
<p>We have become aware in the last decade that microbes spend over 90 percent of their lives as <a href="https://theconversation.com/unlocking-the-secrets-of-bacterial-biofilms-to-use-against-them-59148">biofilms</a>, which may best be thought of as biological tissue. Indeed, many biofilms have systems of <a href="http://www.sci-news.com/biology/science-bacteria-neurons-human-brain-03373.html">electrical communication</a> between cells, like brain tissue, making them a model for studying brain disorders such as migraine and epilepsy.</p>
<p>Biofilms can also be thought of as “<a href="http://doi.org/10.1128/JB.182.10.2675-2679.2000">cities of microbes</a>,” and the integration of <a href="http://doi.org/10.1016/j.tim.2004.11.007">sociomicrobiology</a> and medical research is <a href="http://doi.org/10.1128/microbiolspec.VMBF-0019-2015">making rapid progress</a> in many areas, such as the treatment of cystic fibrosis. The <a href="http://doi.org/10.1146/annurev.ecolsys.38.091206.095740">social lives of microbes</a> in these cities – complete with cooperation, conflict, truth, lies and even <a href="http://blogs.scientificamerican.com/lab-rat/the-bacteria-that-commit-honourable-suicide/">suicide</a> – is fast becoming the major study area in evolutionary biology in the 21st century.</p>
<p>Just as the biology of humans becomes starkly less outstanding than we had thought, the world of microbes gets far more interesting. And the number of genes doesn’t seem to have anything to do with it.</p><img src="https://counter.theconversation.com/content/64284/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sean Nee does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The answer – fewer than are in a banana – has implications for the study of human health and raises questions about what generates complexity anyway.Sean Nee, Research Professor of Ecosystem Science and Management, Penn StateLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/633532016-09-20T10:59:03Z2016-09-20T10:59:03ZHow poor NHS testing and antibiotic use is creating super-strength cystitis<figure><img src="https://images.theconversation.com/files/132653/original/image-20160801-17173-ddukai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Close-up of antibiotic resistant bacteria.</span> <span class="attribution"><span class="source">Kateryna Kon/Shutterstock</span></span></figcaption></figure><p>Urinary tract infections – also known as cystitis – are extremely common. Around <a href="https://www.auanet.org/education/adult-uti.cfm">150m people are affected worldwide</a> each year and one in every three women is expected to suffer at least one attack before they are 24. </p>
<p>But the real figure could actually be somewhere much higher. This is because the urine dipstick, the standard test for cystitis, has been shown to <a href="http://www.ncbi.nlm.nih.gov/pubmed/20303096">miss at least half of all infections</a>. Alongside this, the standard laboratory culture that’s used to check for bacteria in the urine also <a href="http://www.ncbi.nlm.nih.gov/pubmed/23596238">misses around 50% of all infections</a>. And if this wasn’t bad enough, around 20-30% of patients won’t respond to the “<a href="http://www.ncbi.nlm.nih.gov/pubmed/15846726">guideline treatment</a>” of antibiotics.</p>
<p>A lot of these problems can be attributed to <a href="https://www.nice.org.uk/guidance/qs90">current health guidelines</a>, which are out of date and ineffective. And the use of these “guidelines” alongside an over-reliance on poor testing methods means there is a real risk a person with a genuine urinary tract infection (UTI) will be missed and won’t receive adequate treatment. </p>
<p>This can then lead to long-term recurrent infections – and for some patients a lifetime of constant symptoms – which are made worse by sex, exercise, alcohol, certain food and drink, stress and many other of life’s normal events.</p>
<h2>Peeing problems</h2>
<p>UTIs happen when the urinary tract becomes infected, usually by bacteria. In most cases, this is bacteria from the gut, which is found in faeces – this enters the urinary tract through the urethra, the bit where wee comes out of. </p>
<p>This sounds pretty bad but it has nothing to do with hygiene or cleanliness. Anyone can get a UTI, but they’re particularly common in women, and especially common after sex. This is thought to be because a woman’s urethra is shorter than a man’s, and is closer to their anus. </p>
<p>A typical case of cystitis starts after sex, when a woman finds she needs to wee more than usual, and that going for a wee is difficult – it is slow to start and the stream is reduced. These are the <a href="http://arxiv.org/abs/1501.03537">typical early symptoms of a urine infection</a>.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=902&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=902&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=902&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1134&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1134&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132656/original/image-20160801-17165-19hmfl6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1134&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The failing dipstick test.</span>
<span class="attribution"><span class="source">Bork/Shutterstock</span></span>
</figcaption>
</figure>
<p>At this point, lots of people – even doctors – might believe the best advice is to drink plenty of water to “get things going”, but there is no evidence to justify this and it could actually make matters worse. This is because increased fluid intake dilutes the urine of <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC292547/">natural antibodies</a>, immune chemicals and antibiotics. Plus, the offending microbes are stuck to the bladder cells so they cannot be simply washed away.</p>
<p>As the infection progresses, it can lead to pain and burning when going for a wee and a general feeling of discomfort around the bladder. At this point, most people will go to their doctors and will have their urine tested with a <a href="http://www.bpac.org.nz/BT/2013/June/urine-tests.aspx">dipstick</a> – but given these miss at least half of infections it can hardly be considered a reliable method of testing. </p>
<h2>Ignoring the evidence</h2>
<p>Left untreated, patients often become much worse – leading to return visits to the doctor. Another dipstick test at this point might reveal there is a “trace positive result” so the urine is sent to be “cultured” at the hospital – this identifies if there are any germs in the urine that could cause a urinary tract infection. But, again because a high number of infections are missed, culturing urine is also problematic.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132654/original/image-20160801-17165-rb5i1p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It’s a myth that cranberry juice can cure bladder infections.</span>
<span class="attribution"><span class="source">Brent Hofacker/Shutterstock</span></span>
</figcaption>
</figure>
<p>A typical treatment would now be three days of an antibiotic – which could lead to the patient feeling partially better but not cured. This happens in about <a href="http://www.ncbi.nlm.nih.gov/pubmed/15846726">20% to 30% of cases</a>, whether prescribed for three days or 14 days – but we still don’t really know why some people respond and others do not.</p>
<p>At this point, because of the limited nature of current testing methods, a urine culture may well be reported as negative and so “diagnostically” speaking the patient is declared free of infection. This is despite the continued presence of pain and tenderness when the bladder is pressed – indicating signs of infection and inflammation. </p>
<p>From here, if not treated properly, the infection might progress to a hospital admission with <a href="http://www.webmd.com/a-to-z-guides/kidney-infections-symptoms-and-treatments">a kidney infection</a>, or ongoing recurrent infections for the rest of a patient’s life. This recurrence happens because early on in the infection the responsible microbes will have organised themselves into what is known as a “<a href="https://theconversation.com/biofilms-the-bacterial-wound-communities-that-protect-themselves-from-attack-42218">biofilm</a>” which are located on the cell surfaces or inside the bladder cells.</p>
<h2>Hard to beat</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132661/original/image-20160801-17165-1g2f50l.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">How a biofilm develops.</span>
<span class="attribution"><span class="source">struna/Shutterstock</span></span>
</figcaption>
</figure>
<p>Biofilms are capable of protecting “delinquent microbes” from immune attack, and reduce the effectiveness of antibiotics – which is what happens in these types of bladder infections. </p>
<p>This may mean that a higher, longer dosage is needed. This goes against the current guidelines for treatment, and so is often not available to patients.</p>
<p>All of this demonstrates how we have become too reliant on tests, and imagine wrongly that they can give us clear “yes” or “no” answers to ease our doubts – they cannot. Instead, we should get back to the old clinical bedside skills that were developed years ago. </p>
<p>While I have been working in this field I have come to realise that in many cases, clinicians are using poorly equipped tests because the numerous inspectors, governors, guideline enthusiasts and dogmatists compel them to do so. This must change. We need to start scrutinising these long-held beliefs with healthy scepticism, reviewing approaches to diagnosis and patient care, because lives depend on it.</p><img src="https://counter.theconversation.com/content/63353/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>James Malone-Lee 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>Poor testing methods and antibiotic use by GPs and urologists has left thousands of women with crippling infections.James Malone-Lee, Professor of Medicine, Whittington Campus, UCL Medical School, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/635452016-08-08T11:20:18Z2016-08-08T11:20:18ZThe cities of the future could be built by microbes<figure><img src="https://images.theconversation.com/files/133226/original/image-20160805-484-1gz30uv.jpg?ixlib=rb-1.1.0&rect=15%2C22%2C1479%2C1868&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Illustration of pressure sensing bacteria in soils from the 'Computational Colloids Project'. </span> <span class="attribution"><span class="source">Carolina Ramirez-Figuroa, Luis Hernan and Martyn Dade-Robertson</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>You might be disappointed to hear that some intriguing underwater structures <a href="http://www.sciencedirect.com/science/article/pii/S0264817216301611">recently discovered</a> off the Greek island of Zakynthos are not part of the lost city of Atlantis. But the structures, which resemble colonnades of cobble stones and bases of columns, have an equally fascinating origin. They were actually <a href="http://www.scientificamerican.com/article/underwater-lost-city-built-by-microbes/">constructed by microbes</a> gathering around natural vents of methane and forming a natural cement in the otherwise soft sediment.</p>
<p>To some degree, these formations are an accident, sculpted by the interaction of the microorganisms with their physical and chemical environments. But they still point to a complex ability not usually associated with simple single-celled organisms less than 0.0002cm in diameter. So if bacteria can grow their own “cities”, could we use them to grow ours as well?</p>
<p>Bacterial building is actually more common than you might think. If you rub your tongue across the back of your teeth and find a rough spot between the base of the tooth and your gum you should probably go and see a dental hygienist. But you might also contemplate the fact that you have a city growing on your teeth. The rough patch, known more commonly as plaque, <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732559/">is a biofilm</a>, a complex structure built by bacteria living in your mouth.</p>
<p>Biofilms are, in effect, <a href="http://www.sciencedirect.com/science/article/pii/S0925857409001128">buildings for bacteria</a>. They provide the bacteria with physical protection and (unfortunately for us) protection from antibiotics. They also enable a <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732559">complex communications network</a> between the bacteria that lets them work together, with different groups of cells performing different functions and even helping control the populations.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=452&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=452&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133252/original/image-20160805-466-18g44h3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=452&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Underwater microbe ‘cities’ off Zakynthos.</span>
<span class="attribution"><span class="source">University of East Anglia</span></span>
</figcaption>
</figure>
<p>Researchers are now experimenting with using the building abilities of bacteria in the human world. For example, we can make <a href="http://www.citg.tudelft.nl/en/research/projects/self-healing-concrete/">self-healing concretes</a> that use bacteria to re-mineralise cracks. It is even possible to create <a href="http://biomason.com">bacteria-based bio-cements</a> using a process similar to that which built the structures found in Zakynthos.</p>
<p>Both systems use a process known as <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1472-4669.2008.00147.x/abstract">biomineralisation</a>, where bacteria cause mineral crystals to form by changing the chemical composition of their environment. In the case of self-healing concretes and bio-cements, they combine calcium found in their immediate environment with carbon from carbon dioxide in the air. The beauty of the process is that, unlike normal cements and concretes that produce a lot of carbon dioxide, this actually takes carbon out of the atmosphere. </p>
<h2>Under pressure</h2>
<p>Our research takes this idea even further. We want to use the capacity of microorganisms to sense and respond to their environment, as well as add to it with their own structures. For example, imagine if we could lace the ground of a building site with bacteria that react when they feel mechanical pressure by binding the surrounding soil grains. This would mean we could create a self-constructing foundation just by putting the right amount of pressure on the ground, removing the need for costly excavations and reinforced concrete slabs.</p>
<p>Such a system may still be some way into the future but we have started down the path. Through the emerging discipline of <a href="https://theconversation.com/uk/topics/synthetic-biology">synthetic biology</a> we have already been able to identify genes in certain bacteria that activate in response to pressure. We’ve then used genetic engineering to design bacteria <a href="http://www.synbio.construction/2016/07/11/computational-colloids-project-at-seed-2016/">that glow when pressurised</a>. Our next step is to begin to use this pressure-sensing capacity in the bacteria to trigger the the process of biomineralisation and the production of new binding materials including polymers. </p>
<p>The site off Zakynthos may have been an archaeological disappointment but it reveals something about the way we might construct buildings in the future. Imagine visiting the ancient remains of our microbial-built future cities. When the archaeologists assess whether they are natural or artificial they may not be able to tell.</p><img src="https://counter.theconversation.com/content/63545/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martyn Dade-Robertson receives funding from the Engineering and Physical Sciences Research Council (EPSRC) for the project 'Comutational Colloids'. EPSRC Reference: EP/N005791/1.</span></em></p>Bacteria can produce their own ‘buildings’ so scientists are genetically engineering them to build ours.Martyn Dade-Robertson, Reader in Design Computation, Co-director of the Architectural Research Collaborative, Newcastle UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/591482016-06-01T01:00:21Z2016-06-01T01:00:21ZUnlocking the secrets of bacterial biofilms – to use against them<figure><img src="https://images.theconversation.com/files/124356/original/image-20160527-894-iuv5a8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's bacterial biofilms that give the Grand Prismatic Spring its colorful hues.</span> <span class="attribution"><span class="source">Karin Sauer</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Standing on a walkway at Yellowstone National Park, I admired the hues of orange, blue and yellow in the sand of the Grand Prismatic Spring. A small sign nearby read “bacterial mats.” Visitors to Yellowstone may have noticed similar signs all over the park, but they’re often overlooked on the way to waterfalls, geysers, hot springs and more.</p>
<p>But these colorful structures at my feet were the reason I had come. Well, I needed a vacation – and what better place then Yellowstone? – but professional curiosity had a lot to do with the destination. I’m a microbiologist, and I had come to see the bacterial mats.</p>
<p>More commonly known as biofilms, these communities of tightly packed bacteria grow in close association with surfaces such as sand and soil. The term “biofilms” suggests a thin, two-dimensional substance, but these communities feature microscopic-scale tower-like structures crisscrossed with water channels, all of which is encased in a protective, self-produced slimy layer. The bacteria within communicate and demonstrate cooperative behavior reminiscent of primitive organs.</p>
<p>As visually stunning as I find these biofilms in nature, these bacterial communities can be detrimental to human health. Scientists like me are investigating how these bacterial biofilms form and behave so we can figure out new ways to manage and control them.</p>
<h2>Biofilms are all around us</h2>
<p>While made up of bacteria that are invisible to the naked eye, biofilms themselves can be much bigger, ranging from less than an inch to several hundred feet in size. Yellowstone is home to the most extensive and most colorful biofilms I’ve ever seen, but these bacterial communities are not unique to the park. Biofilms are found anywhere in nature, visible as <a href="http://genomealberta.ca/blogs/curiosity-about-stromatolites-and-biofilm.aspx">stromatolites</a>, pond scum and the slimy, slippery layer coating rocks and pebbles in streams.</p>
<p>And biofilms are not limited to the environment, either, since bacteria will stick to almost any surface in aqueous conditions and encase themselves with a slime matrix. Indeed, biofilms pose <a href="http://dx.doi.org/10.1080/87559129209540953">numerous problems to human-made materials</a> such as ship hulls, cooling towers, sewage treatment plants, oil refineries, food processing and beverage plants, and household plumbing. You’ve likely seen them yourself while cleaning or doing repairs in your kitchen or bathroom, as a thick and slimy buildup in your drains and pipes. Biofilms can be a real nuisance, <a href="http://www.slideshare.net/mfornalik/intro-to-biofilms-3522031">causing biofouling and corrosion</a>.</p>
<p>The <a href="http://dx.doi.org/10.1126/science.284.5418.1318">ubiquity of biofilms</a> in our surroundings is supported by findings that the majority of bacteria, up to 90 percent, prefer <a href="http://www.ncbi.nlm.nih.gov/pubmed/340020">living in surface-associated biofilm communities</a> rather than as free-floating, individual bacteria (what we call planktonic bacteria).</p>
<p>So why do bacteria <a href="http://dx.doi.org/10.1128/JB.00003-12">tend to form communities</a>? For one thing, there’s strength in numbers. By banding together within their slimy protection, biofilm bacteria can remain in favorable locations or hosts, better withstand nutrient deprivation, stress, dessication and predation. At the same time, they benefit from increased cooperation and exchange of genetic material.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/124520/original/image-20160530-7692-10riis.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">Scanning electron micrograph of part of a central venous catheter, removed from a patient, that was colonized by a biofilm of rod-shaped bacteria associated with fibrinlike material on the catheter’s surface.</span>
<span class="attribution"><a class="source" href="http://phil.cdc.gov/">Janice Haney Carr</a></span>
</figcaption>
</figure>
<h2>Biofilms can harm human health</h2>
<p>Biofilms have been linked to contamination of <a href="http://dx.doi.org/10.1089/10445490260099700">contact lenses leading to corneal ulcers</a>. They’re associated with <a href="http://dx.doi.org/10.1177/0022034510368644">dental plaque that leads to caries and periodontitis</a>. <a href="http://dx.doi.org/10.1126/science.284.5418.1318">They can infect</a> <a href="http://dx.doi.org/10.1007/978-3-319-09782-4">surgical sites</a>, the urinary tract, chronic and burn wounds and the lungs of cystic fibrosis patients. And they love to <a href="http://dx.doi.org/10.1016/B978-0-323-22805-3.00005-0">colonize medical devices</a> such as catheters, prosthetic joints and heart valves.</p>
<p>According to the National Institutes of Health, more than 65 percent of <a href="http://dx.doi.org/10.1111/2049-632X.12151">chronic inflammatory and infectious diseases</a> are due to biofilms. According to research, biofilm-related infections claim as many lives as heart attack or cancer. And they are costly, with treatment of biofilm-related infections <a href="http://dx.doi.org/10.1002/bit.21838">ranging into the billions</a> annually worldwide.</p>
<p>Why are we not better equipped to treat such bacterial infections? Research by my laboratory and others has demonstrated that when bacteria attach to a surface and grow as biofilms, they undergo a change, as evidenced by the genes they express and the proteins they produce. One of the consequences of this change is that biofilm bacteria become less susceptible to biocides, disinfectants and antibiotics. </p>
<p>Scientists think there are several reasons for this decrease in susceptibility. First, the slimy layer encasing biofilms can make it hard for disinfectants or antimicrobials to even physically reach the bacteria. Also, bacteria living in biofilms experience high stress levels while growing rather slowly, which can render most antibiotics ineffective since they only work on actively growing cells. My favorite theory is that living in a biofilm changes bacteria and their behavior; something about their mix of active genes and proteins just makes them more resilient. Whatever the contributing factors, bacteria growing in a biofilm can be <a href="http://dx.doi.org/10.1128/JB.00765-12">up to 1,000-fold more resistant to antibiotics</a> than the same bacteria grown planktonically.</p>
<p>This profound tolerance to antimicrobial agents – a hallmark of biofilms – is at the root of many persistent infections and renders biofilms extremely difficult to control in medical settings. <a href="http://www.ncbi.nlm.nih.gov/books/NBK84450/">Conventional therapies have proven inadequate</a> in the treatment of many if not most chronic biofilm infections, mainly because they have been geared toward bacteria growing planktonically and not as biofilms.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=264&fit=crop&dpr=1 600w, https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=264&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=264&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=332&fit=crop&dpr=1 754w, https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=332&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/124591/original/image-20160531-1943-1tkghh6.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=332&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 formation of surface-associated biofilm communities (A) can be prevented or significantly reduced (B) by interfering with key factors required for their development. Bacterial cells are stained green.</span>
<span class="attribution"><span class="source">Karin Sauer</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>New lines of attack against biofilms</h2>
<p>Research suggests a promising new avenue for biofilm control: the manipulation of the biofilm lifestyle. Yes, for bacteria, being in a biofilm is a lifestyle choice.</p>
<p>The biofilm way of life is initiated when a few planktonic bacteria adhere to a surface. Once attached, these bacteria will divide and grow into more complex, three-dimensional structures – the biofilm. If resources become exhausted or the biofilm become too overcrowded, bacteria can escape it, as a means of survival and dissemination.</p>
<p>It’s the two extremes of their lifestyle, the beginning and the end, attachment and escape, that have become major foci of research endeavors looking for ways to defeat biofilms.</p>
<p>When it comes to controlling attachment, much research has focused on the <a href="http://dx.doi.org/10.1111/j.1574-695X.2011.00858.x">development of new surface materials</a> aimed at preventing the formation of biofilms on medical devices in the first place. The idea is to render devices’ surfaces nonsticky, repelling or otherwise toxic for those first pioneering bacteria. If they can’t latch on and get a toehold, no biofilm can eventually form. Surface coatings containing colloidal silver, antibiotics or micro-brushes can render medical devices inhospitable.</p>
<p>Likewise, the hunt is on for new chemical compounds that prevent attachment or induce escape strategies. Researchers are <a href="http://dx.doi.org/10.1128/JB.01214-08">starting to have some success</a>.</p>
<p><a href="http://bingweb.binghamton.edu/%7Eksauer/">My own research</a>, along with that of colleagues at Binghamton University and around the world, has led me down another path. I’ve been trying to understand how bacteria actually make these amazing biofilm structures. What proteins, polymers and factors do they need to coordinate their lifestyle? What have we learned that would let us manipulate this biofilm lifestyle?</p>
<p>It’s unlikely there will be only one effective treatment strategy to defeat biofilms. For one thing, many varieties of bacteria form biofilms, and they all use somewhat different strategies to enable this lifestyle. For instance, while bacteria may coordinate the formation of biofilms via chemical signals, the molecules used by bacteria such as <em>E. coli</em> or <em>S. aureus</em> to do so differ quite dramatically. Likewise with the species-specific sets of proteins required to coordinate the formation of each kind of biofilm. So as we target individual characteristics, some of our tactics work better on one group than another. </p>
<p>But biofilm bacteria also share some common features that we can take advantage of, including their need for communication and coordination. Building a biofilm, escaping from the biofilm or even living in a biofilm requires some sort of coordination among the millions of bacteria that make it up. They can do so by communicating with each other, using a chemical language or proteins. Jamming the bacterial language (although there are many) or interfering with their key factors required for coordination has proven to be a successful strategy to block or modify biofilm formation, at least in laboratory settings and some clinical pilot studies.</p>
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<a href="https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/124590/original/image-20160531-1943-iim40a.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=377&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Biofilms before (A) and after (B) exposure to ‘Escape from the biofilm!’ chemical signal. Note the biofilms in (B) are hollow, appearing like empty shells. Bacterial cells are stained in green.</span>
<span class="attribution"><span class="source">Karin Sauer</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Likewise, repurposing the bacterial language has shown promise. For instance, when we co-opt the bacterial language to signal “<a href="http://dx.doi.org/10.1128/JB.01214-08">escape from the biofilm!</a>” we can trick biofilm bacteria into giving up their protective lifestyle and converting to planktonic cells again. The added benefit is the planktonic cells are more susceptible to antibiotics.</p>
<p>Controlling biofilms in the future will likely require a combination of strategies, addressing both attachment and escape, with and without the use of antibiotics and communication blockers, and likely in a manner more or less tailored toward the different bacterial lifestyles.</p><img src="https://counter.theconversation.com/content/59148/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>My research is currently supported by grants from the National Institute of Health and F. Hoffmann-La Roche Ltd.
</span></em></p>The vast majority of the bacteria that surround us are not free-floating but prefer to band together in cooperative communities called biofilms. How do biofilms form and cooperate?Karin Sauer, Professor of Biological Sciences, Binghamton University, State University of New YorkLicensed as Creative Commons – attribution, no derivatives.