{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:13:18Z","timestamp":1790737998015,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010581","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI120489"],"award-info":[{"award-number":["AI120489"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI157106"],"award-info":[{"award-number":["AI157106"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM124724"],"award-info":[{"award-number":["GM124724"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32-AI-055400"],"award-info":[{"award-number":["T32-AI-055400"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Vibrio cholerae<\/jats:italic> is the etiologic agent of the severe human diarrheal disease cholera. To colonize mammalian hosts, this pathogen must defend against host-derived toxic compounds, such as nitric oxide (NO) and NO-derived reactive nitrogen species (RNS). RNS can covalently add an NO group to a reactive cysteine thiol on target proteins, a process called protein S-nitrosylation, which may affect bacterial stress responses. To better understand how <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> regulates nitrosative stress responses, we profiled <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> protein S-nitrosylation during RNS exposure. We identified an S-nitrosylation of cysteine 235 of AphB, a LysR-family transcription regulator that activates the expression of <jats:italic>tcpP<\/jats:italic>, which activates downstream virulence genes. Previous studies show that AphB C235 is sensitive to O<jats:sub>2<\/jats:sub> and reactive oxygen species (ROS). Under microaerobic conditions, AphB formed dimer and directly repressed transcription of <jats:italic>hmpA<\/jats:italic>, encoding a flavohemoglobin that is important for NO resistance of <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic>. We found that tight regulation of <jats:italic>hmpA<\/jats:italic> by AphB under low nitrosative stress was important for <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> optimal growth. In the presence of NO, S-nitrosylation of AphB abolished AphB activity, therefore relieved <jats:italic>hmpA<\/jats:italic> expression. Indeed, non-modifiable <jats:italic>aphB<\/jats:italic><jats:sup>C235S<\/jats:sup> mutants were sensitive to RNS <jats:italic>in vitro<\/jats:italic> and drastically reduced colonization of the RNS-rich mouse small intestine. Finally, AphB S-nitrosylation also decreased virulence gene expression via debilitation of <jats:italic>tcpP<\/jats:italic> activation, and this regulation was also important for <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> RNS resistance <jats:italic>in vitro<\/jats:italic> and in the gut. These results suggest that the modulation of the activity of virulence gene activator AphB via NO-dependent protein S-nitrosylation is critical for <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> RNS resistance and colonization.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010581","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T17:39:38Z","timestamp":1655487578000},"page":"e1010581","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["S-Nitrosylation of the virulence regulator AphB promotes Vibrio cholerae pathogenesis"],"prefix":"10.1371","volume":"18","author":[{"given":"Jiandong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuntae","family":"Byun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianxuan","family":"She","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Gustav","family":"Ruggeberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinqin","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Ji","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary R.","family":"Brockett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansel","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9182-5224","authenticated-orcid":true,"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"issue":"10101","key":"ppat.1010581.ref001","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/S0140-6736(17)30559-7","article-title":"Cholera","volume":"390","author":"JD Clemens","year":"2017","journal-title":"Lancet"},{"issue":"12","key":"ppat.1010581.ref002","doi-asserted-by":"crossref","first-page":"5542","DOI":"10.1128\/IAI.01094-07","article-title":"Regulatory networks controlling Vibrio cholerae virulence gene expression","volume":"75","author":"JS 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