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

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Abstract
Deletion of the mexAB-oprM multidrug efflux operon substantially compromised the β-lactam resistance of β-lactamase-derepressed mutants of Pseudomonas aeruginosa, although it had only a modest impact on resistance of a penicillin-binding protein mutant. This highlights the multifactorial nature of β-lactam resistance in this organism. Moreover, the contribution of efflux to the net resistance seen in some β-lactam-resistant mutants suggests that inhibition of MexAB-OprM-mediated drug efflux might be an effective approach to overcoming β-lactam resistance attributed to efflux as well as to other mechanisms of β-lactam resistance.