Influence of the MexA-MexB-OprM multidrug efflux system on expression of the MexC-MexD-OprJ and MexE-MexF-OprN multidrug efflux systems in Pseudomonas aeruginosa

Of the Pseudomonas aeruginosa multidrug efflux systems, MexAB-OprM is expressed in wild-type cells, while MexCD-OprJ is not, and MexEF-OprN shows variable, strain-specific expression. In defined mutant strains, MexCD-OprJ expression increased with decreases in MexAB-OprM and was generally inversely related to MexAB-OprM expression. In so-called wild-type strains expressing MexEF-OprN, MexAB-OprM hyperexpression correlated with a decline in MexEF-OprN expression, while loss of MexAB-OprM was associated with increased expression of MexEF-OprN, also indicative of an inverse correlation between MexAB-OprM and MexEF-OprN expression. Still, the increases in MexCD-OprJ and MexEF-OprN failed to compensate for the loss of MexAB-OprM with respect to antibiotic resistance. Nonetheless, these data suggest that the overall complement of these MDR efflux systems is monitored and that alterations in the level of one efflux system may effect compensatory changes in the levels of the others.