title: Chlorinated phenols control the expression of the multidrug resistance efflux pump MexAB-OprM in Pseudomonas aeruginosa 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.
authors.affiliation: Department of Civil and Environmental Engineering, University of Michigan, 2350 Hayward Street, 2340 GG Brown, Ann Arbor, MI 48109-2125, USA.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Ghosh
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Cremers
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Love
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010416:Pentachlorophenol / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D010416:Pentachlorophenol