Contribution of the MexAB-OprM multidrug efflux system to the beta-lactam resistance of penicillin-binding protein and beta-lactamase-derepressed mutants of Pseudomonas aeruginosa

Deletion of the mexAB-oprM multidrug efflux operon substantially compromise d the beta-lactam resistance of beta-lactamase-derepressed mutants of Pseud omonas aeruginosa, although it had only a modest impact on resistance of a penicillin-binding protein mutant. This highlights the multifactorial natur e of beta-lactam resistance in this organism. Moreover, the contribution of efflux to the net resistance seen in some beta-lactam-resistant mutants su ggests that inhibition of MexAB-OprM-mediated drug efflux might be an effec tive approach to overcoming beta-lactam resistance attributed to efflux as well as to other mechanisms of beta-lactam resistance.