{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:20:02Z","timestamp":1781583602673,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010102","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007709","name":"Michigan State University","doi-asserted-by":"publisher","award":["Rudolph Hugh Endowment"],"award-info":[{"award-number":["Rudolph Hugh Endowment"]}],"id":[{"id":"10.13039\/100007709","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007709","name":"Michigan State University","doi-asserted-by":"publisher","award":["Eleanor L. Gilmore Endowed Excellence Award"],"award-info":[{"award-number":["Eleanor L. Gilmore Endowed Excellence Award"]}],"id":[{"id":"10.13039\/100007709","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> respires both aerobically and anaerobically and, while oxygen may be available to it during infection, other terminal electron acceptors are proposed for population expansion during infection. Unlike gastrointestinal pathogens that stimulate significant inflammation leading to elevated levels of oxygen or alternative terminal electron acceptors, <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> infections are not understood to induce a notable inflammatory response. To ascertain the respiration requirements of <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> during infection, we used Multiplex Genome Editing by Natural Transformation (MuGENT) to create <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> strains lacking aerobic or anaerobic respiration. <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> strains lacking aerobic respiration were attenuated in infant mice 10<jats:sup>5<\/jats:sup>-fold relative to wild type, while strains lacking anaerobic respiration had no colonization defect, contrary to earlier work suggesting a role for anaerobic respiration during infection. Using several approaches, including one we developed for this work termed Comparative Multiplex PCR Amplicon Sequencing (CoMPAS), we determined that the <jats:italic>bd-<\/jats:italic>I and <jats:italic>cbb<\/jats:italic><jats:sub>3<\/jats:sub> oxidases are essential for small intestinal colonization of <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> in the infant mouse. The <jats:italic>bd<\/jats:italic>-I oxidase was also determined as the primary oxidase during growth outside the host, making <jats:italic>V<\/jats:italic>. <jats:italic>cholerae<\/jats:italic> the only example of a Gram-negative bacterial pathogen in which a <jats:italic>bd<\/jats:italic>-type oxidase is the primary oxidase for energy acquisition inside and outside of a host.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010102","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T17:34:57Z","timestamp":1651512897000},"page":"e1010102","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Vibrio cholerae requires oxidative respiration through the bd-I and cbb3 oxidases for intestinal proliferation"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-049X","authenticated-orcid":true,"given":"Andrew J.","family":"Van Alst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas M.","family":"Demey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3617-7011","authenticated-orcid":true,"given":"Victor J.","family":"DiRita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,2]]},"reference":[{"key":"ppat.1010102.ref001","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41579-020-00486-4","article-title":"Architecture of bacterial respiratory chains","volume":"19","author":"VRI Kaila","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1010102.ref002","first-page":"2466","volume-title":"Lancet","author":"Cholera"},{"issue":"9","key":"ppat.1010102.ref003","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nrmicro1476","article-title":"The genomic code: inferring Vibrionaceae niche specialization","volume":"4","author":"FJ Reen","year":"2006","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"ppat.1010102.ref004","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1038\/s41564-018-0253-0","article-title":"Anaerobic nitrate reduction divergently governs population expansion of the enteropathogen Vibrio cholerae","volume":"3","author":"E Bueno","year":"2018","journal-title":"Nat Microbiol"},{"issue":"47","key":"ppat.1010102.ref005","doi-asserted-by":"crossref","first-page":"39742","DOI":"10.1074\/jbc.M112.394932","article-title":"Activation of cholera toxin production by anaerobic respiration of trimethylamine N-oxide in Vibrio cholerae","volume":"287","author":"K-M Lee","year":"2012","journal-title":"J Biol Chem"},{"issue":"5","key":"ppat.1010102.ref006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.01989-20","article-title":"Aerobic metabolism in Vibrio cholerae is required for population expansion during infection","volume":"11","author":"AJ Van Alst","year":"2020","journal-title":"MBio"},{"issue":"24","key":"ppat.1010102.ref007","doi-asserted-by":"crossref","first-page":"e00243","DOI":"10.1128\/JB.00243-20","article-title":"Genetic dissection of the fermentative and respiratory contributions supporting Vibrio cholerae hypoxic growth","volume":"202","author":"E Bueno","year":"2020","journal-title":"J Bacteriol"},{"issue":"6","key":"ppat.1010102.ref008","doi-asserted-by":"crossref","first-page":"C350","DOI":"10.1152\/ajpcell.00191.2015","article-title":"Physiologic hypoxia and oxygen homeostasis in the healthy intestine. 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