期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 36, 页码 13586-13591出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803391105
关键词
antibiotic resistance regulation; thiol modification; MarR; oxidative stress; transcription regulation
资金
- National Institute of Allergy and Infectious Diseases/National Institutes of Health [R01 A1074658]
- National Science Foundation Award [MCB-0547854]
- University of Chicago
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 A 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 A aeruginosa.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据