Interplay between the MexA-MexB-OprM multidrug efflux system and the outermembrane barrier in the multiple antibiotic resistance of Pseudomonas aeruginosa

MexAB-OprM is a constitutively expressed multidrug efflux system of Pseudom onas aeruginosa, Using isogenic pump mutants, the contributions of the MexA B-OprM efflux pump and the outer membrane barrier to multiple antibiotic re sistance were evaluated by assessing the influence of pump inactivation and outer membrane permeabilization on antibiotic susceptibility. Both pump in activation and increased outer membrane permeability enhanced antibiotic su sceptibility, although maximal susceptibility was achieved when the two wer e combined. Thus, inhibition of antibiotic efflux pumps and permeabilizatio n of the outer membrane constitute an effective approach to reversing the a ntibiotic resistance of this organism.