{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:07:50Z","timestamp":1791223670797,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            infections caused by strains that are resistant to all forms of penicillin, so-called methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            (MRSA) strains, have become common. One strategy to counter MRSA infections is to use compounds that resensitize MRSA to methicillin.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            responds to diverse classes of cell wall-inhibitory antibiotics, like methicillin, using the two-component regulatory system VraSR (\n            <jats:italic>vra<\/jats:italic>\n            ) to up- or downregulate a set of genes (the cell wall stimulon) that presumably facilitates resistance to these antibiotics. Accordingly, VraS and VraR mutations decrease resistance to methicillin, vancomycin, and daptomycin cell wall antimicrobials.\n            <jats:italic>vraS<\/jats:italic>\n            and\n            <jats:italic>vraR<\/jats:italic>\n            are encoded together on a transcript downstream of two other genes, which we call\n            <jats:italic>vraU<\/jats:italic>\n            and\n            <jats:italic>vraT<\/jats:italic>\n            (previously called\n            <jats:italic>yvqF<\/jats:italic>\n            ). By producing nonpolar deletions in\n            <jats:italic>vraU<\/jats:italic>\n            and\n            <jats:italic>vraT<\/jats:italic>\n            in a USA300 MRSA clinical isolate, we demonstrate that\n            <jats:italic>vraT<\/jats:italic>\n            is essential for optimal expression of methicillin resistance\n            <jats:italic>in vitro<\/jats:italic>\n            , whereas\n            <jats:italic>vraU<\/jats:italic>\n            is not required for this phenotype. The deletion of\n            <jats:italic>vraT<\/jats:italic>\n            also improved the outcomes of oxacillin therapy in mouse models of lung and skin infection. Since\n            <jats:italic>vraT<\/jats:italic>\n            expressed in\n            <jats:italic>trans<\/jats:italic>\n            did not complement a\n            <jats:italic>vra<\/jats:italic>\n            operon deletion, we conclude that VraT does not inactivate the antimicrobial. Genome-wide transcriptional microarray experiments reveal that VraT facilitates resistance by playing a necessary regulatory role in the VraSR-mediated cell wall stimulon. Our data prove that VraTSR comprise a novel three-component regulatory system required to facilitate resistance to cell wall agents in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            . We also provide the first\n            <jats:italic>in vivo<\/jats:italic>\n            proof of principle for using VraT as a sole target to resensitize MRSA to \u03b2-lactams.\n          <\/jats:p>","DOI":"10.1128\/aac.01651-12","type":"journal-article","created":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T05:51:17Z","timestamp":1350366677000},"page":"83-95","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":112,"title":["VraT\/YvqF Is Required for Methicillin Resistance and Activation of the VraSR Regulon in Staphylococcus aureus"],"prefix":"10.1128","volume":"57","author":[{"given":"Susan","family":"Boyle-Vavra","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, Illinois, USA"},{"name":"Sections of Infectious Disease, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouhui","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, Illinois, USA"},{"name":"Sections of Infectious Disease, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Sun","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, Illinois, USA"},{"name":"Sections of Infectious Disease, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, Illinois, USA"},{"name":"Critical Care, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Daum","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago, Chicago, Illinois, USA"},{"name":"Sections of Infectious Disease, University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.15.1763"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00081-09"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044194"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68233-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.11.4289-4294.2002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0908.030089"},{"key":"e_1_3_3_8_2","first-page":"322","article-title":"Vancomycin-resistant Staphylococcus aureus\u2014New York, 2004","volume":"53","author":"CDC","year":"2004","unstructured":"CDC. 2004. 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