Roles of MexXY- and MexAB-multidrug efflux pumps in intrinsic multidrug resistance of Pseudomonas aeruginosa PAO1

To envisage the roles of MexXY- and MexAB-multidrug efflux pumps in the intrinsic multidrug resistance of wild-type strain Pseudomonas aeruginosa PAO1, we constructed mutants lacking either individual or both efflux pumps, A mutant lacking MexXY showed increased susceptibility to aminoglycosides, erythromycin, and tetracycline, but not to beta -lactams, chloramphenicol, or quinolones. A mutant lacking MexAB showed increased susceptibility to beta -lactams, chloramphenicol, and nalidixic acid, but not to aminoglycosides, erythromycin, tetracycline, or fluoroquinolones, A mutant lacking both MexXY and MexAB showed an increased susceptibility to all antimicrobial agents tested compared with the wild type. Very similar results were obtained with a mutant lacking MexAB-OprM and a mutant lacking both MexXY and MexAB-OprM, Thus it is clear that OprM is essential not only for the function of MexAB, but also for the function of MexXY, Furthermore, we found that each pump compensated to some extent for the lack of another pump with respect to the common substrates (tetracycline, quinolones, and cefpirome), The introduction of a plasmid carrying the mexXY genes into P. aeruginosa PAO1 cells increased the resistance to fluoroquinolones, This suggests that the mexXY genes could be involved in acquired resistance to fluoroquinolones in P. aeroginosa PAO1.