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Colonization of the intestine depends upon the expression of genes that allow\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            to overcome host barriers, including low pH, bile acids, and the innate immune system. ToxR is a major contributor to this process. ToxR is a membrane-spanning transcription factor that coordinates gene expression in response to environmental cues. In previous work we showed that ToxR upregulated\n            <jats:italic>leuO<\/jats:italic>\n            expression in response to bile salts. LeuO is a LysR family transcription factor that contributes to acid tolerance, bile resistance, and biofilm formation in\n            <jats:named-content content-type=\"genus-species\">V. cholerae<\/jats:named-content>\n            . Here, we investigated the function of ToxR and LeuO in cationic antimicrobial peptide (CAMP) resistance. We report that ToxR and LeuO contribute to CAMP resistance by regulating\n            <jats:italic>carRS<\/jats:italic>\n            transcription. CarRS is a two-component regulatory system that positively regulates\n            <jats:italic>almEFG<\/jats:italic>\n            expression. AlmEFG confers CAMP resistance by glycinylation of lipid A. We found that the expression of\n            <jats:italic>carRS<\/jats:italic>\n            and\n            <jats:italic>almEFG<\/jats:italic>\n            and the polymyxin B MIC increased in mutants lacking\n            <jats:italic>toxRS<\/jats:italic>\n            or\n            <jats:italic>leuO<\/jats:italic>\n            . Conversely,\n            <jats:italic>leuO<\/jats:italic>\n            overexpression decreased the polymyxin B MIC. Furthermore, we found that LeuO directly bound to the\n            <jats:italic>carRS<\/jats:italic>\n            promoter and that ToxR-dependent activation of\n            <jats:italic>leuO<\/jats:italic>\n            transcription regulated\n            <jats:italic>carRS<\/jats:italic>\n            transcription in response to bile salts. Our results suggest that LeuO functions downstream of ToxR to modulate\n            <jats:italic>carRS<\/jats:italic>\n            expression in response to environmental cues. This study extends the functional role of ToxR and LeuO in environmental adaptation to include cell surface remodeling and CAMP resistance.\n          <\/jats:p>","DOI":"10.1128\/iai.00445-16","type":"journal-article","created":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T02:39:00Z","timestamp":1471919940000},"page":"3161-3171","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes"],"prefix":"10.1128","volume":"84","author":[{"given":"X. 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