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Despite the critical role of CTX\u03c6 during infections, signals that affect CTX\u03c6\u2010driven toxigenic conversion or expression of the CTX\u03c6\u2010encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTX\u03c6\u2010driven pathogenicity in\n                    <jats:italic>V.\u00a0cholerae.<\/jats:italic>\n                    Our results indicate that mucin\u2010associated\n                    <jats:italic>O\u2010<\/jats:italic>\n                    glycans block toxigenic conversion by CTX\u03c6 and suppress the expression of CTX\u03c6\u2010related virulence factors, including the toxin co\u2010regulated pilus and cholera toxin, by interfering with the TcpP\/ToxR\/ToxT virulence pathway. By synthesizing individual mucin glycan structures\n                    <jats:italic>de novo<\/jats:italic>\n                    , we identify the Core 2 motif as the critical structure governing this virulence attenuation. Overall, our results highlight a novel mechanism by which mucins and their associated\n                    <jats:italic>O<\/jats:italic>\n                    \u2010glycan structures affect CTX\u03c6\u2010mediated evolution and pathogenicity of\n                    <jats:italic>V.\u00a0cholerae<\/jats:italic>\n                    , underscoring the potential regulatory power housed within mucus\n                    <jats:italic>.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.15252\/embj.2022111562","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T06:00:06Z","timestamp":1670824806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Host\u2010derived O\u2010glycans inhibit toxigenic conversion by a virulence\u2010encoding phage in Vibrio cholerae"],"prefix":"10.1038","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5270-6043","authenticated-orcid":false,"given":"Benjamin X","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"McShane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Hwan","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0029-4291","authenticated-orcid":false,"given":"Kazuhiro","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1017-0690","authenticated-orcid":false,"given":"Catherine","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Teschler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giordan","family":"Kitts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulietta","family":"Minzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-9143","authenticated-orcid":false,"given":"Michael","family":"Tiemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2649-3427","authenticated-orcid":false,"given":"Rachel","family":"Hevey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitnat","family":"Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-338X","authenticated-orcid":false,"given":"Katharina","family":"Ribbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"BFEMBJ2022111562_CR1","doi-asserted-by":"crossref","first-page":"9127","DOI":"10.1074\/jbc.M606711200","volume":"282","author":"K Aoki","year":"2007","unstructured":"Aoki K, Perlman M, Lim J\u2010M, Cantu R, Wells L, Tiemeyer M (2007) Dynamic developmental elaboration of N\u2010linked glycan complexity in the Drosophila melanogaster embryo. 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