{"id":1186,"date":"2014-07-24T20:00:42","date_gmt":"2014-07-24T18:00:42","guid":{"rendered":"http:\/\/news.embl.de\/?p=1186"},"modified":"2024-11-14T16:32:35","modified_gmt":"2024-11-14T15:32:35","slug":"1407_cdiff","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/","title":{"rendered":"Fighting bacteria \u2013 with viruses"},"content":{"rendered":"\n<p>Research by scientists from EMBL Hamburg reveals how enzymes from bacteriophages \u2013 viruses that infect and destroy bacteria, but do not affect other organisms \u2013 are triggered and released to degrade cell walls of the bacteria <em>Clostridium difficile <\/em>(<em>C. diff<\/em>). Published today in <em>PLoS Pathogens<\/em>, the work adds crucial information to our understanding of the bacteriophage infection pathway, and opens up new opportunities for developing effective therapies to overcome issues raised by antibiotic resistance.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Side-stepping antibiotics<\/h3>\n\n\n\n<p><em>C. diff<\/em>, is becoming a serious problem in hospitals and healthcare institutes, where it can cause life-threatening cases of diarrhoea. Patients who receive broad-spectrum antibiotic treatment are particularly at risk. <em>C. diff<\/em> naturally occurs in human gut flora and poses no problem in healthy individuals, but in patients treated with antibiotics, a large amount of gut bacteria are wiped out allowing the more resistant and persistent <em>C. diff<\/em> to increase uncontrollably in number, leading to complications. Such cases are very difficult to treat, precisely because <em>C.diff<\/em> is unresponsive to many antibiotics.<\/p>\n\n\n\n<p>A potential alternative treatment for <em>C. diff<\/em> infections would be to use bacteriophages. These bacteria-infecting viruses were discovered as treatment for bacterial infections over 100 years ago but became less popular as antibiotics \u2013 which were easier to use and store \u2013 became available. Now, with the increase in antibiotic resistance, bacteriophage research and therapies are experiencing a revival.<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image alignnone wp-image-1190 size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"620\" height=\"380\" class=\"vf-figure__image\" src=\"http:\/\/news.embl.de\/wp-content\/uploads\/2014\/07\/1407_Cdiff_3.jpg\" alt=\"Bacteriophages\" class=\"wp-image-1190\" srcset=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/07\/1407_Cdiff_3.jpg 620w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/07\/1407_Cdiff_3-300x184.jpg 300w\" sizes=\"auto, (max-width: 620px) 100vw, 620px\" \/><figcaption class=\"vf-figure__caption\">Electron microscopy image of the bacteriophages investigated. IMAGE: KATHRYN CROSS\/IFR<\/figcaption><\/figure>\n\n\n\n<p>Bacteriophages enter a bacterial cell and hijack that cell\u2019s DNA replication machinery to reproduce. The cell then breaks up, releasing the newly formed bacteriophages. In order to develop and engineer effective bacteriophage therapies, a clear understanding of the viruses\u2019 life cycle is needed \u2013 in particular, how the bacterial cell wall is destroyed. While it is known that the enzymes involved, called endolysins, are produced at the end of the bacteriophage life cycle directly before the break-up of the cell, just how these enzymes are activated remains a crucial missing part of the puzzle. Understanding this mechanism would allow researchers to engineer effective bacteriophage treatments.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>A common switch<\/strong><\/h3>\n\n\n\n<p>In this study, Rob Meijers and <a href=\"http:\/\/www.embl-hamburg.de\/research\/unit\/meijers\" target=\"_blank\" rel=\"noopener noreferrer\">his group<\/a> at EMBL Hamburg report a common activation mechanism for bacteriophage endolysins that target <em>Clostridium<\/em> bacteria like <em>C.diff<\/em>. In collaboration with Melinda Mayer and <a href=\"http:\/\/www.ifr.ac.uk\/research\/scientists\/arjan-narbad\/\" target=\"_blank\" rel=\"noopener noreferrer\">Arjan Narbad<\/a> from the Institute of Food Research in Norwich, UK, the scientists compared two endolysins. One was retrieved from a bacteriophage that infects <em>C. diff<\/em>, and the other digests the cell wall of a <em>Clostridium<\/em> species that impairs cheese fermentation. At the <a href=\"https:\/\/www.desy.de\/index_eng.html\" target=\"_blank\" rel=\"noopener noreferrer\">German Electron Synchrotron (DESY)<\/a> in Hamburg, the EMBL researchers used X-ray crystallography and small angle X-ray scattering \u2013 techniques which involve shining X-ray beams on a sample and measuring how that sample interferes with those rays \u00ad\u2013 to deduce the enzymes&#8217; 3-dimensional structure. From that 3D structure, Meijers and colleagues were able to infer how the endolysins work.<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image alignnone size-full wp-image-1189\"><img loading=\"lazy\" decoding=\"async\" width=\"620\" height=\"380\" class=\"vf-figure__image\" src=\"http:\/\/news.embl.de\/wp-content\/uploads\/2014\/07\/1407_Cdiff_2.jpg\" alt=\"Structure of viral endolysin\" class=\"wp-image-1189\" srcset=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/07\/1407_Cdiff_2.jpg 620w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/07\/1407_Cdiff_2-300x184.jpg 300w\" sizes=\"auto, (max-width: 620px) 100vw, 620px\" \/><figcaption class=\"vf-figure__caption\">The viral endolysins are activated by switching from a tensed, stretched state (left) to a relaxed state (right).<br \/>Credit: EMBL\/ROB MEIJERS<\/figcaption><\/figure>\n\n\n\n<p>\u201cThese enzymes seem to take on two different conformations,\u201d explains Matthew Dunne, a PhD student in Meijers\u2019 lab who carried out the research. \u201cThey appear to switch from a tense, elongated shape where a pair of endolysins are joined together, to a relaxed state where the two endolysins lie side-by-side.\u201d The switch from one state to the other triggers the release of the active enzyme, which then begins to degrade the cell wall. Once the cell wall begins to break down, the bacterial cell can no longer withstand its own internal pressure and explodes, releasing the new bacteriophages that go on to infect other bacteria. The group believes environmental influences trigger the release and activation mechanism.<\/p>\n\n\n\n<p>\u201cRemarkably, we found that the two endolysins have a common activation mechanism,\u201d explains Meijers. It therefore seems likely that this mechanism is not restricted to <em>Clostridia<\/em>-specific bacteriophages, but can be found in many others, too. \u201cThis knowledge could allow us to engineer effective, specific bacteriophages, not just for <em>C. diff <\/em>infections, but for a wide range of pathogenic bacteria related to human health, agriculture and the food industry. In the light of increased antibiotic resistance, bacteriophages and their endolysins may provide a good alternative.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Molecular switch enables viruses to destroy C.diff bacteria \u2013 potential alternative to antibiotics<\/p>\n","protected":false},"author":18,"featured_media":1188,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[29,53,100,34,75,1748,35],"embl_taxonomy":[],"class_list":["post-1186","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-crystallography","tag-hamburg","tag-meijers","tag-pathogen","tag-phd","tag-press-release","tag-structural-biology"],"acf":{"article_intro":"<p>Scientists show how bacteriophages destroy <em>Clostridium difficile<\/em> cells, opening up new possibilities for using viruses as an alternative to antibiotics.<\/p>\n","related_links":false,"article_sources":[{"source_description":"<p>Dunne, M., <em>et al.<\/em> <em>PLoS Pathogens<\/em>, 24 July 2014.<\/p>\n","source_link_url":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1004228."}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Fighting bacteria \u2013 with viruses | EMBL<\/title>\n<meta name=\"description\" content=\"Molecular switch enables viruses to destroy C.diff bacteria \u2013 potential alternative to antibiotics\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Fighting bacteria \u2013 with viruses | EMBL\" \/>\n<meta property=\"og:description\" content=\"Molecular switch enables viruses to destroy C.diff bacteria \u2013 potential alternative to antibiotics\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2014-07-24T18:00:42+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-11-14T15:32:35+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/07\/1407_Cdiff_1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"465\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Rosemary Wilson\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@rawilson80\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Rosemary Wilson\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/\"},\"author\":{\"name\":\"Rosemary Wilson\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/bb5e57a6c6c5c3b33a6a40b2d4c96e40\"},\"headline\":\"Fighting bacteria \u2013 with viruses\",\"datePublished\":\"2014-07-24T18:00:42+00:00\",\"dateModified\":\"2024-11-14T15:32:35+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/\"},\"wordCount\":698,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1407_cdiff\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/07\/1407_Cdiff_1.jpg\",\"keywords\":[\"crystallography\",\"hamburg\",\"meijers\",\"pathogen\",\"phd\",\"press release\",\"structural biology\"],\"articleSection\":[\"Science\",\"Science &amp; 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