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RpoS, an alternative sigma factor, plays a central role in spirochetal adaptation to the mammalian host by governing expression of many genes important for mammalian infection.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>\n            is known to be unique in metal utilization, and little is known of the role of biologically available metals in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>\n            . Here, we identified two transition metal ions, manganese (Mn\n            <jats:sup>2+<\/jats:sup>\n            ) and zinc (Zn\n            <jats:sup>2+<\/jats:sup>\n            ), that influenced regulation of RpoS. The intracellular Mn\n            <jats:sup>2+<\/jats:sup>\n            level fluctuated approximately 20-fold under different conditions and inversely correlated with levels of RpoS and the major virulence factor OspC. Furthermore, an increase in intracellular Mn\n            <jats:sup>2+<\/jats:sup>\n            repressed temperature-dependent induction of RpoS and OspC; this repression was overcome by an excess of Zn\n            <jats:sup>2+<\/jats:sup>\n            . Conversely, a decrease of intracellular Mn\n            <jats:sup>2+<\/jats:sup>\n            by deletion of the Mn\n            <jats:sup>2+<\/jats:sup>\n            transporter gene,\n            <jats:italic>bmtA<\/jats:italic>\n            , resulted in elevated levels of RpoS and OspC. Mn\n            <jats:sup>2+<\/jats:sup>\n            affected RpoS through BosR, a Fur family homolog that is required for\n            <jats:italic>rpoS<\/jats:italic>\n            expression: elevated intracellular Mn\n            <jats:sup>2+<\/jats:sup>\n            levels greatly reduced the level of BosR protein but not the level of\n            <jats:italic>bosR<\/jats:italic>\n            mRNA. Thus, Mn\n            <jats:sup>2+<\/jats:sup>\n            and Zn\n            <jats:sup>2+<\/jats:sup>\n            appeared to be important in modulation of the RpoS pathway that is essential to the life cycle of the Lyme disease spirochete. This finding supports the emerging notion that transition metals such as Mn\n            <jats:sup>2+<\/jats:sup>\n            and Zn\n            <jats:sup>2+<\/jats:sup>\n            play a critical role in regulation of virulence in bacteria.\n          <\/jats:p>","DOI":"10.1128\/iai.00507-13","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T02:54:23Z","timestamp":1369104863000},"page":"2743-2752","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Manganese and Zinc Regulate Virulence Determinants in Borrelia burgdorferi"],"prefix":"10.1128","volume":"81","author":[{"given":"Bryan","family":"Troxell","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiping","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Key Laboratory of Laboratory Medicine, School of Laboratory Medicine, Wenzhou Medical College, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian E.","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Lou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, School of Laboratory Medicine, Wenzhou Medical College, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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