Chlorinated phenols control the expression of the multidrug resistance efflux pump MexAB–OprM in <i>Pseudomonas aeruginosa</i> by interacting with NalC

Abstract

NalC is a TetR type regulator that represses the multidrug efflux pump MexAB-OprM in Pseudomonas aeruginosa. Here we explain the mechanism of NalC-mediated regulation of MexAB-OprM. We show that NalC non-covalently binds chlorinated phenols and chemicals containing chlorophenol side-chains such as triclosan. NalC-chlorinated phenol binding results in its dissociation from promoter DNA and upregulation of NalC's downstream targets, including the MexR antirepressor ArmR. ArmR upregulation and MexR-ArmR complex formation have previously been shown to upregulate MexAB-OprM. In vivo mexB and armR expression analyses were used to corroborate in vitro NalC-chlorinated phenol binding. We also show that the interaction between chlorinated phenols and NalC is reversible, such that removal of these chemicals restored NalC promoter DNA binding. Thus, the NalC-chlorinated phenol interaction is likely a pertinent physiological mechanism that P. aeruginosa uses to control expression of the MexAB-OprM efflux pump.