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

摘要

To envisage the roles of MexXY- and MexAB-multidrug efflux pumps in the intrinsic multidrug re- sistance of wild-type strain Pseudomonas aeruginosa PAO1 , we constructed mutants lacking ei- ther individual or both efflux pumps. A mutant lacking MexXY showed increased susceptibility to aminoglycosides, erythromycin, and tetracycline, but not to !3-lactams, chloramphenicol, or quinolones. A mutant lacking MexAB showed increased susceptibility to !3-lactams, chloram- phenicol, and nalidixic acid, but not to aminoglycosides, erythromycin, tetracycline, or fluoro- quinolones. 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 an- other 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 fiuoroquinolones. This suggests that the mexXY genes could be involved in ac- quired resistance to fiuoroquinolones in P. aeruginosa PAO1.