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

MexAB-OprM is a constitutively expressed multidrug efflux system of Pseudomonas aeruginosa. Using isogenic pump mutants, the contributions of the MexAB-OprM efflux pump and the outer membrane barrier to multiple antibiotic resistance were evaluated by assessing the influence of pump inactivation and outer membrane permeabilization on antibiotic susceptibility. Both pump inactivation and increased outer membrane permeability enhanced antibiotic susceptibility, although maximal susceptibility was achieved when the two were combined. Thus, inhibition of antibiotic efflux pumps and permeabilization of the outer membrane constitute an effective approach to reversing the antibiotic resistance of this organism.