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Within the bacterial inner membrane<\/a>, MurJ normally flips critical wall-building material to the cell\u2019s outer side, a motion that keeps the protective barrier intact.\u00a0<\/p>\n By resolving three virus-bound forms of MurJ, Professor William M. Clemons Jr. at the California Institute of Technology (Caltech<\/a>) demonstrated that distinct viral proteins all clamp onto the same groove and lock the transporter facing outward.\u00a0<\/p>\n In every case, the protein remains stuck in that outward-facing state, unable to complete the movement required to deliver new wall<\/a> components.\u00a0<\/p>\n Such repeated interference at a single site suggests that this exposed position is not incidental, but central to how MurJ can be stopped.<\/p>\n The wall bottleneck<\/p>\n Bacteria stay intact because peptidoglycan<\/a>, a stiff mesh that gives bacteria shape, keeps cells from bursting, and humans do not make it.<\/p>\n MurJ handles a key wall precursor, moving it from the inner side of the membrane to the outside. <\/p>\n When that transporter stalls, the supply of wall pieces stops at the membrane, and the outer wall never thickens.<\/p>\n \u201cPeptidoglycan is a unique feature of bacteria, and that makes it an attractive antibiotic target,\u201d said Clemons.<\/p>\n Tiny genes, big damage<\/p>\n To burst out of a host, bacteria<\/a>-infecting viruses must stop wall building fast enough to rupture cells.<\/p>\n Some carry single-gene lysis proteins \u2013 small killers encoded by one gene \u2013 and researchers call them Sgls.<\/p>\n Instead of making many tools, an Sgl wedges into the membrane and shuts down one essential machine, like MurJ.<\/p>\n That one-hit strategy lets viruses succeed with minimal genetic baggage, and it also points scientists toward drug targets.<\/p>\n Three paths converge<\/p>\n Even though their genomes differ, the three Sgls disable MurJ using the same strategy \u2013 an example of convergent evolution.<\/p>\n Despite having no shared sequence, the third lysis protein came from an environmental dataset and still matched the same MurJ groove.<\/p>\n \u201cThis is a third genome that evolved a distinct peptide to inhibit the same target in a similar way,\u201d said Clemons.<\/p>\n Repeated hits on the same target<\/a> suggest this transporter is a weak spot, and other viruses may reveal additional vulnerabilities.<\/p>\n Freezing MurJ in place<\/p>\n To catch MurJ mid-motion, the team used cryo-EM \u2013 frozen imaging that maps proteins in fine detail \u2013 and saw the gate stuck open.<\/p>\n A pocket inside the transporter normally opens inward to grab a wall precursor, then swings outward to release it.<\/p>\n Each Sgl bound along the groove between two membrane helices, blocking the pivoting movement that powers the flip.<\/p>\n Those cryo-EM maps highlighted small pockets and charged spots on MurJ that could anchor a drug built for fit.<\/p>\n Why exposure matters<\/p>\n For Gram-negative bacteria, microbes with an extra outer membrane, drug molecules often struggle to reach inner wall machinery.<\/p>\n In that stuck-open pose, MurJ opened toward the space between the two membranes, not the cell interior.<\/p>\n Because the pocket faced that gap, a drug could bind without crossing the inner membrane, though the outer barrier remains.<\/p>\n Such access could make MurJ easier to target than hidden enzymes, but any inhibitor still must survive blood and metabolism.<\/p>\n Blueprint for antibiotics<\/p>\n Drug designers can treat the three Sgls as templates, since each one fits MurJ tightly. <\/p>\n Their binding surfaces outline a pocket lined with charged residues, giving chemists clear contact points to target.<\/p>\n Lab screens can now search for small molecules that sit in that pocket, then test whether bacteria stop growing.<\/p>\n Turning that map into a real pill will take years of chemistry, because peptide toxins rarely make safe medicines.<\/p>\n Resistance keeps rising<\/p>\n Nationwide, a Centers for Disease Control and Prevention report<\/a> estimated that more than 35,000 people die yearly from resistant infections.<\/p>\n \u201cIn the U.S. alone, tens of thousands of people die every year from antibiotic-resistant bacterial infections, and that number is rising rapidly,\u201d said Clemons.<\/p>\n Globally, an analysis<\/a> estimated 1.27 million deaths directly tied to bacterial drug resistance in 2019. <\/p>\n With resistance spreading and new antibiotics arriving slowly, targets highlighted by viruses could keep future infections treatable.<\/p>\n Hidden antibiotic clues<\/p>\n Millions of virus<\/a> genomes now sit in sequence databases, and many likely encode undiscovered Sgls with bacterial weak spots.<\/p>\n By expressing these tiny genes in bacteria, labs can watch which cells burst, then trace the protein target.<\/p>\n From environmental samples, new viruses can surface without ever being grown, and cryo-EM can still reveal their tactics.<\/p>\n Each time a virus points to a vulnerable bacterial part, drug developers gain another option when older antibiotics fail.<\/p>\n From discovery to treatment<\/p>\n A shared viral solution has now pinned MurJ as a controllable choke point, and its exposed pocket offers a practical blueprint.<\/p>\n Next steps include designing small molecules that hold MurJ in that frozen pose, then testing whether bacteria evolve escape routes.<\/p>\n The study is published in Nature<\/a>.<\/p>\n \u2014\u2013<\/p>\n Like what you read?\u00a0Subscribe to our newsletter<\/a>\u00a0for engaging articles, exclusive content, and the latest updates.<\/p>\n Check us out on\u00a0EarthSnap<\/a>, a free app brought to you by\u00a0Eric Ralls<\/a>\u00a0and Earth.com.<\/p>\n \u2014\u2013<\/p>\n","protected":false},"excerpt":{"rendered":"Three unrelated viruses have been shown to kill bacteria by trapping the cell-wall transporter MurJ, which flips essential…\n","protected":false},"author":2,"featured_media":327703,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[61,60,82],"class_list":{"0":"post-327702","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science","8":"tag-ie","9":"tag-ireland","10":"tag-science"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/327702","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=327702"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/327702\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/327703"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=327702"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=327702"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=327702"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}