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Here we studied the mechanisms involved in palmitic acid resistance and their impact on in vivo biological fitness in a murine genital tract infection model. A stable palmitic acid-resistant derivative was obtained by serial passage with incremental palmitic acid concentrations. This derivative outcompeted its parent strain for colonization and survival in the murine infection model. Subsequent whole-genome sequencing resulted in the identification of the 3 resistance-related SNPs ihfAC5T, fadDC772T, and farAG-52T (promoter) that were verified for resistance against palmitic acid. Subsequent characterization of the associated resistance determinants showed that ihfAC5T and farAG-52T induced gene expression of the FarAB efflux pump, whereas fadDC772T increased the maximum enzyme activity of the FadD long-chain fatty acid-coenzyme A ligase. Our results highlight the mechanisms involved in gonococcal adaptation to the murine host environment.<\/jats:p>","DOI":"10.1093\/infdis\/jiaa701","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T12:08:28Z","timestamp":1604491708000},"page":"141-150","source":"Crossref","is-referenced-by-count":5,"title":["Gonococcal Adaptation to Palmitic Acid Through <i>farAB<\/i> Expression and FadD Activity Mutations Increases In Vivo Fitness in a Murine Genital Tract Infection Model"],"prefix":"10.1093","volume":"224","author":[{"given":"Lingyu","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhemin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8176-391X","authenticated-orcid":false,"given":"Stijn","family":"van der Veen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China"},{"name":"Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"key":"2021070214464143100_CIT0001","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1071\/SH19023","article-title":"World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts","volume":"16","author":"Unemo","year":"2019","journal-title":"Sex Health"},{"key":"2021070214464143100_CIT0002","volume-title":"Report on global sexually transmitted infection surveillance","author":"World Health Organization (WHO)","year":"2018"},{"key":"2021070214464143100_CIT0003","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1128\/CMR.17.4.965-981.2004","article-title":"The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women","volume":"17","author":"Edwards","year":"2004","journal-title":"Clin Microbiol Rev"},{"key":"2021070214464143100_CIT0004","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0091-7435(02)00058-0","article-title":"Asymptomatic sexually transmitted diseases: the case for screening","volume":"36","author":"Farley","year":"2003","journal-title":"Prev Med"},{"key":"2021070214464143100_CIT0005","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1099\/13500872-141-3-611","article-title":"Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system","volume":"141","author":"Hagman","year":"1995","journal-title":"Microbiology (Reading)"},{"key":"2021070214464143100_CIT0006","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1046\/j.1365-2958.1999.01530.x","article-title":"The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids","volume":"33","author":"Lee","year":"1999","journal-title":"Mol Microbiol"},{"key":"2021070214464143100_CIT0007","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1128\/iai.37.2.432-438.1982","article-title":"Gonococcal strains from homosexual men have outer membranes with reduced permeability to hydrophobic molecules","volume":"37","author":"Morse","year":"1982","journal-title":"Infect Immun"},{"key":"2021070214464143100_CIT0008","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1073\/pnas.95.4.1829","article-title":"Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance\/nodulation\/division efflux pump family","volume":"95","author":"Shafer","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021070214464143100_CIT0009","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s00253-009-2355-3","article-title":"Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential","volume":"85","author":"Desbois","year":"2010","journal-title":"Appl Microbiol Biotechnol"},{"key":"2021070214464143100_CIT0010","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1194\/jlr.R700016-JLR200","article-title":"Thematic review series: skin lipids. 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