Knock-out of multidrug efflux pump MexXY-OprM results in increased susceptibility to antimicrobial peptides in Pseudomonas aeruginosa

Abstract

Multidrug efflux systems of the resistance-nodulation-cell division family play a crucial role in resistance of Pseudomonas aeruginosa to a large variety of antibiotics. Here, we investigated the role of clinically relevant efflux pumps MexAB^- OprM, MexCD^- OprJ, and MexXY^- OprM in resistance against different cationic antimicrobial peptides (AMPs). Our results indicate that a knock-out in efflux pump MexXY-OprM increased susceptibility to some AMPs by two- to eightfold. Our data suggest a contribution of MexXY-OprM in resistance to certain AMPs in P. aeruginosa, which should be considered in the future development of new and highly active antimicrobial peptides to fight multidrug resistant infections.

Keywords: MexXY-OprM; Pseudomonas aeruginosa; antimicrobial peptides; efflux pump.