β-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity

被引：275

作者：

Gutierrez, A. ^{[1
]}

Laureti, L. ^{[1
]}

Crussard, S. ^{[1
]}

Abida, H. ^{[1
]}

Rodriguez-Rojas, A. ^{[2
]}

Blazquez, J. ^{[2
]}

Baharoglu, Z. ^{[3
]}

Mazel, D. ^{[3
]}

Darfeuille, F. ^{[4
]}

Vogel, J. ^{[5
]}

Matic, I. ^{[1
]}

机构：

[1] Univ Paris 05, INSERM, U1001, Sorbonne Paris Cite,Fac Med Paris Descartes, 24 Rue Faubourg St Jacques, F-75014 Paris, France

[2] Ctr Nacl Biotecnol, Dept Biotecnol Microbiana, Madrid 28049, Spain

[3] Inst Pasteur, CNRS, Unite Plasticite Genome Bacterien, Dept Genome & Genet,UMR3525, F-75015 Paris, France

[4] Univ Bordeaux Segalen, INSERM, U869, F-33076 Bordeaux, France

[5] Univ Wurzburg, Inst Mol Infect Biol, D-97080 Wurzburg, Germany

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

DNA-POLYMERASE-IV; GENERAL STRESS-RESPONSE; ESCHERICHIA-COLI K-12; SIGMA(S)-DEPENDENT GENES; MULTIDRUG-RESISTANCE; ADAPTIVE MUTATION; SIGMA-FACTOR; CELL-DEATH; EXPRESSION; EVOLUTION;

D O I：

10.1038/ncomms2607

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：

Regardless of their targets and modes of action, subinhibitory concentrations of antibiotics can have an impact on cell physiology and trigger a large variety of cellular responses in different bacterial species. Subinhibitory concentrations of beta-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli. Here we show that subinhibitory concentrations of beta-lactam antibiotics induce the RpoS regulon. RpoS-regulon induction is required for PolIV-dependent mutagenesis because it diminishes the control of DNA-replication fidelity by depleting MutS in E. coli, Vibrio cholerae and Pseudomonas aeruginosa. We also show that in E. coli, the reduction in mismatch-repair activity is mediated by SdsR, the RpoS-controlled small RNA. In summary, we show that mutagenesis induced by subinhibitory concentrations of antibiotics is a genetically controlled process. Because this mutagenesis can generate mutations conferring antibiotic resistance, it should be taken into consideration for the development of more efficient antimicrobial therapeutic strategies.

引用

页数：9

共 60 条

[41] Stress-Induced β-Lactam Antibiotic Resistance Mutation and Sequences of Stationary-Phase Mutations in the Escherichia coli Chromosome [J].