The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids

Gonococci often infect mucosal surfaces bathed in antibacterial fatty acids (FAs). Resistance of gonococci to FAs and other antibacterial hydrophobic agents has been attributed to the mtrCDE-encoded efflux pump system and a h eretofore undefined mechanism. This alternative resistance mechanism has be en suggested to mediate gonococcal resistance to long-chained FAs independe ntly of the mtr efflux pump. We have now identified this alternative FA res istance system in gonococci and report that it bears significant similarity to the emrAB-encoded efflux pump possessed by Escherichia coli and the vce AB-encoded pump of Vibrio cholerae. We termed the gonococcal version of thi s efflux pump farAB (fatty acid resistance) to signify its involvement in F A resistance expressed by gonococci and to distinguish it from the emrAB- o r vceAB-encoded pumps that modulate bacterial susceptibility to uncoupling agents and certain antibiotics. Although the farAB system in gonococci was found to provide resistance to Fns independently of the mtrCDE-encoded effl ux pump, its function was dependent on the MtrE outer membrane protein. Mor eover, expression of the tandemly linked farA and farB genes was positively associated with the presence of the MtrR transcriptional regulatory protei n that normally down-regulates the expression of mtrCDE. Thus, the data pre sented herein suggest that, while the mtrCDE- and farAB-encoded systems act independently to mediate resistance of gonococci to host-derived, hydropho bic antimicrobial agents, their capacity to export these agents is dependen t on the same outer membrane protein (MtrE), and their expression may be di fferentially controlled by the same transcriptional regulatory protein (Mtr R).