{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:35:15Z","timestamp":1791218115889,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T00:00:00Z","timestamp":1444780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R01-AI091779"],"award-info":[{"award-number":["R01-AI091779"]}]},{"name":"Pathogenesis of Infectious Diseases Award"},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["15PRE22710027"],"award-info":[{"award-number":["15PRE22710027"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Group A Streptococcus (<jats:styled-content style=\"fixed-case\">GAS<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>S<\/jats:italic><\/jats:styled-content><jats:italic>treptococcus pyogenes<\/jats:italic>) is a human\u2010restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when <jats:styled-content style=\"fixed-case\">GAS<\/jats:styled-content> switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (<jats:styled-content style=\"fixed-case\">CovRS<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">CsrRS<\/jats:styled-content>) two\u2010component system and the <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>gg2\/3 quorum\u2010sensing pathway. We demonstrate that responses of <jats:styled-content style=\"fixed-case\">CovRS<\/jats:styled-content> to the stress signals <jats:styled-content style=\"fixed-case\"><jats:roman>Mg<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> and a fragment of the antimicrobial peptide <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037 result in modulated activity of pheromone signaling of the <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>gg2\/3 pathway through a means of proteolysis of <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content> peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase <jats:styled-content style=\"fixed-case\">PepO<\/jats:styled-content>, which is the first identified enzymatic silencer of an <jats:styled-content style=\"fixed-case\">RRNPP<\/jats:styled-content>\u2010type quorum\u2010sensing pathway. These results suggest that under conditions in which the virulence potential of <jats:styled-content style=\"fixed-case\">GAS<\/jats:styled-content> is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>gg2\/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>gg2\/3 signaling is instead functional during non\u2010virulent <jats:styled-content style=\"fixed-case\">GAS<\/jats:styled-content> lifestyles.<\/jats:p>","DOI":"10.1111\/mmi.13216","type":"journal-article","created":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T11:41:39Z","timestamp":1441885299000},"page":"71-87","source":"Crossref","is-referenced-by-count":52,"title":["<scp>PepO<\/scp>, a <scp>CovRS<\/scp>\u2010controlled endopeptidase, disrupts <scp><i>S<\/i><\/scp><i>treptococcus pyogenes<\/i> quorum sensing"],"prefix":"10.1111","volume":"99","author":[{"given":"Reid V.","family":"Wilkening","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine University of Illinois at Chicago  Chicago IL 60607 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy Center for Biomolecular Sciences College of Pharmacy University of Illinois at Chicago  Chicago IL 60607 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Federle","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy Center for Biomolecular Sciences College of Pharmacy University of Illinois at Chicago  Chicago IL 60607 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