The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism

被引：116

作者：

Chen, Hao ^{[1
]}

Hu, Jie ^{[1
]}

Chen, Peng R. ^{[1
]}

Lan, Lefu ^{[1
]}

Li, Zigang ^{[1
]}

Hicks, Leslie M. ^{[2
]}

Dinner, Aaron R. ^{[1
]}

He, Chuan ^{[1
]}

机构：

[1] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[2] Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 36期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

antibiotic resistance regulation; thiol modification; MarR; oxidative stress; transcription regulation;

D O I：

10.1073/pnas.0803391105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 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.

引用

页码：13586 / 13591

页数：6

共 43 条

[1] The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 Å resolution [J].