{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:12:04Z","timestamp":1790745124040,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007018","name":"Kimberly-Clark Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Toxic shock syndrome toxin\u20101 (TSST\u20101) is a superantigen (SAg) produced by <jats:italic>Staphylococcus aureus<\/jats:italic> thought to be responsible for essentially all cases of menstrual\u2010associated toxic shock syndrome (TSS). As a potent exotoxin, it is not surprising that <jats:italic>S. aureus<\/jats:italic> has evolved multiple systems to control expression of TSST\u20101. Although the accessory gene regulator (Agr) system is recognized to enhance TSST\u20101 expression, how Agr regulates TSST\u20101 is unclear. Using an <jats:italic>agr<\/jats:italic>\u2010null mutant, complementation experiments demonstrated that Agr controls TSST\u20101 expression through the activity of the RNAIII effector molecule. RNAIII can repress translation of the repressor of toxins (Rot) regulator, and deletion of <jats:italic>rot<\/jats:italic> increased expression of TSST\u20101 during the exponential phase of growth. Deletion of <jats:italic>agr<\/jats:italic> did not affect <jats:italic>rot<\/jats:italic> transcription, but did result in overexpression of the Rot protein, and Rot was also shown to bind and positively regulate the <jats:italic>rot<\/jats:italic> promoter. Overexpression of Rot dramatically repressed TSST\u20101, and Rot bound directly to the TSST\u20101 promoter. Deletion of both <jats:italic>agr<\/jats:italic> and <jats:italic>rot<\/jats:italic> in <jats:italic>S. aureus<\/jats:italic> returned TSST\u20101 expression to wild\u2010type levels. This work demonstrates that Agr, although widely considered to be an inducer of TSST\u20101, has evolved in combination with Rot, to restrict the expression of this potent SAg.<\/jats:p>","DOI":"10.1111\/mmi.14353","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T09:21:43Z","timestamp":1563528103000},"page":"1163-1177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Regulation of toxic shock syndrome toxin\u20101 by the accessory gene regulator in <i>Staphylococcus aureus<\/i> is mediated by the repressor of toxins"],"prefix":"10.1111","volume":"112","author":[{"given":"Stephen W.","family":"Tuffs","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Herfst","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Western Ontario London Ontario Canada"},{"name":"Lawson Health Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren L.","family":"Baroja","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Western Ontario London Ontario Canada"},{"name":"Lawson Health Research Institute London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladyslav A.","family":"Podskalniy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N.","family":"DeJong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E. 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