Gonococcal Adaptation to Palmitic Acid Through farAB Expression and FadD Activity Mutations Increases In Vivo Fitness in a Murine Genital Tract Infection Model

Neisseria gonorrhoeae is a bacterial pathogen that colonizes mucosal epithelia that are rich in antimicrobial molecules such as long-chain fatty acids. 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 ihfA(CST), fadD(C772T), and farA(G-)(52T) (promoter) that were verified for resistance against palmitic acid. Subsequent characterization of the associated resistance determinants showed that ihfA(CST) and farA(G-)(52T) induced gene expression of the FarAB efflux pump, whereas fadD(C772T) 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.

Automated summary

The study elucidated the mechanisms of Neisseria gonorrhoeae resistance to palmitic acid. A stable palmitic acid-resistant strain obtained through serial passage outcompeted its parent strain in a murine infection model, with resistance-related SNPs and determinants enhancing gene expression of the FarAB efflux pump and enzyme activity of the FadD enzyme.