Molecular mechanism of MexR-mediated regulation of MexAB-OprM efflux pump expression in Pseudomonas aeruginosa.

To elucidate the molecular mechanism by which the MexR repressor regulates expression of the MexAB-OprM efflux pump, we investigated MexR and the mexR-mexA intergenic DNA (mexOP) interaction, and transcription of the mexA-lacZ reporter gene containing different lengths of mexOP. Homogeneously purified MexR bound specifically to mexOP proximal to mexR. The mexOP-lacZ fusion gene lacking the region immediately proximal to mexR showed minimum enzyme activity, thereby suggesting that a promoter element is located between mexR and the MexR-binding sites. These observations explain the mechanism of self-regulation of mexR expression as well as low and elevated expression of MexAB-OprM in the wild-type strain and nalB-type mutant, respectively, of Pseudomonas aeruginosa.