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The El Tor and classical biotypes of O1 <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> show striking differences in their resistance to membrane disrupting cationic antimicrobial peptides (CAMPs), such as polymyxins. The classical biotype is susceptible to CAMPs, but current pandemic El Tor biotype isolates gain CAMP resistance by altering the net charge of their cell surface through glycine modification of lipid A. Here we report a second lipid A modification mechanism that only functions in the <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> El Tor biotype. We identify a functional EptA ortholog responsible for the transfer of the amino\u2010residue phosphoethanolamine (pEtN) to the lipid A of <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> El Tor that is not functional in the classical biotype. We previously reported that mildly acidic growth conditions (pH 5.8) downregulate expression of genes encoding the glycine modification machinery. In this report, growth at pH 5.8 increases expression of <jats:italic>eptA<\/jats:italic> with concomitant pEtN modification suggesting coordinated regulation of these LPS modification systems. Similarly, efficient pEtN lipid A substitution is seen in the absence of lipid A glycinylation. We further demonstrate EptA orthologs from non\u2010<jats:italic>cholerae Vibrio<\/jats:italic> species are functional.<\/jats:p>","DOI":"10.1111\/mmi.13835","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T12:12:46Z","timestamp":1505391166000},"page":"582-596","source":"Crossref","is-referenced-by-count":29,"title":["Novel coordination of lipopolysaccharide modifications in <i>Vibrio cholerae<\/i> promotes CAMP resistance"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8343-4837","authenticated-orcid":false,"given":"Carmen M.","family":"Herrera","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Center for Vaccines and Immunology University of Georgia, College of Veterinary Medicine Athens GA 30602 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy C.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Center for Vaccines and Immunology University of Georgia, College of Veterinary Medicine Athens GA 30602 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Crofts","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, Institute for Cellular and Molecular Biology The University of Texas at Austin  TX 78712 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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