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Updated: Jul 2, 2026

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
Published on: February 17, 2014
The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism
Hao Chen1, Jie Hu, Peng R Chen
1Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
Abstract:
MexR is a MarR family protein that negatively regulates multidrug efflux systems in the human pathogen Pseudomonas aeruginosa. The mechanism of MexR-regulated antibiotic resistance has never been elucidated in the past. We present here that two Cys residues in MexR are redox-active. They form intermonomer disulfide bonds in MexR dimer with a redox potential of -155 mV. This MexR oxidation leads to its dissociation from promoter DNA, derepression of the mexAB-oprM drug efflux operon, and increased antibiotic resistance of P. aeruginosa. We show computationally that the formation of disulfide bonds is consistent with a conformation change that prevents the oxidized MexR from binding to DNA. Collectively, the results reveal that MexR is a redox regulator that senses peroxide stress to mediate antibiotic resistance in P. aeruginosa.
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