文章基本信息

标题：The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism
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作者：Hao Chen ; Jie Hu ; Peng R. Chen 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：36
页码：13586-13591
DOI：10.1073/pnas.0803391105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：antibiotic resistance regulation ; thiol modification ; MarR ; oxidative stress ; transcription regulation