{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:48:02Z","timestamp":1787611682465,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012578","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01AI114378"],"award-info":[{"award-number":["U01AI114378"]}],"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":["U19AI113170"],"award-info":[{"award-number":["U19AI113170"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"NCATS","doi-asserted-by":"crossref","award":["TL1TR002491"],"award-info":[{"award-number":["TL1TR002491"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"NCATS","doi-asserted-by":"crossref","award":["UL1TR001111"],"award-info":[{"award-number":["UL1TR001111"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"NCATS","doi-asserted-by":"crossref","award":["K12TR004416"],"award-info":[{"award-number":["K12TR004416"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI021150"],"award-info":[{"award-number":["R01AI021150"]}],"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>The MtrCDE efflux pump of <jats:italic>Neisseria gonorrhoeae<\/jats:italic> exports a wide range of antimicrobial compounds that the gonococcus encounters at mucosal surfaces during colonization and infection and is a known gonococcal virulence factor. Here, we evaluate the role of this efflux pump system in strain FA1090 during <jats:italic>in vivo<\/jats:italic> human male urethral infection with <jats:italic>N. gonorrhoeae<\/jats:italic> using a controlled human infection model. With the strategy of competitive infections initiated with mixtures of wild-type FA1090 and an isogenic mutant FA1090 strain that does not contain a functional MtrCDE pump, we found that the presence of the efflux pump is not required for an infection to be established in the human male urethra. This finding contrasts with previous studies of <jats:italic>in vivo<\/jats:italic> infection in the lower genital tract of female mice, which demonstrated that mutant gonococci of a different strain (FA19) lacking a functional MtrCDE pump had a significantly reduced fitness compared to their wild-type parental FA19 strain. To determine if these conflicting results are due to strain or human <jats:italic>vs<\/jats:italic>. mouse differences, we conducted a series of systematic competitive infections in female mice with the same FA1090 strains as in humans, and with FA19 strains, including mutants that do not assemble a functional MtrCDE efflux pump. Our results indicate the fitness advantage provided by the MtrCDE efflux pump during infection of mice is strain dependent. Owing to the equal fitness of the two FA1090 strains in men, our experiments also demonstrated the presence of a colonization bottleneck of <jats:italic>N. gonorrhoeae<\/jats:italic> in the human male urethra, which may open a new area of inquiry into <jats:italic>N. gonorrhoeae<\/jats:italic> infection dynamics and control.<\/jats:p>\n<jats:p><jats:bold>TRIAL REGISTRATION<\/jats:bold>. Clinicaltrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03840811\" xlink:type=\"simple\">NCT03840811<\/jats:ext-link>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012578","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T19:28:05Z","timestamp":1727292485000},"page":"e1012578","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Experimental genital tract infection demonstrates Neisseria gonorrhoeae MtrCDE efflux pump is not required for in vivo human infection and identifies gonococcal colonization bottleneck"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9219-6570","authenticated-orcid":true,"given":"Andreea","family":"Waltmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline T.","family":"Balthazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrin A.","family":"Begum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann E.","family":"Jerse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia M.","family":"Hobbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-2018","authenticated-orcid":true,"given":"Joseph A.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"issue":"5","key":"ppat.1012578.ref001","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1111\/j.1365-2958.1995.tb02325.x","article-title":"Importance of lipooligosaccharide structure in determining gonococcal resistance to hydrophobic antimicrobial agents resulting from the mtr efflux system","volume":"16","author":"CE Lucas","year":"1995","journal-title":"Mol Microbiol"},{"issue":"3","key":"ppat.1012578.ref002","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1099\/13500872-141-3-611","article-title":"Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic 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