β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity.
β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity.
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DOI：
10.1038/ncomms2607
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发表时间：
2013
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
不管它们的目标和作用方式如何，抗生素的亚抑制浓度可以对细胞生理产生影响，并在不同的细菌物种中引发各种各样的细胞反应。β-内酰胺类抗生素的亚抑制浓度导致大肠杆菌产生活性氧并诱导poliv依赖性突变。本研究表明，β-内酰胺类抗生素的亚抑制浓度可诱导RpoS调控。由于在大肠杆菌、霍乱弧菌和铜绿假单胞菌中，rpos调控诱导降低了对dna复制保真度的控制，因此poliv依赖性突变需要rpos调控诱导。我们还发现，在大肠杆菌中，错配修复活性的降低是由rpos控制的小RNA SdsR介导的。总之，我们表明由抗生素的亚抑制浓度诱导的诱变是一个遗传控制的过程。由于这种诱变可以产生具有抗生素耐药性的突变，因此在开发更有效的抗菌治疗策略时应考虑到这一点。已知亚致死浓度的抗生素会促进细菌DNA的突变。在这里，作者表明β-内酰胺类抗生素通过上调应激反应蛋白RpoS触发突变，RpoS下调错配修复活性。
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 β-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli. Here we show that subinhibitory concentrations of β-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. Sub-lethal concentrations of antibiotics are known to promote mutagenesis of bacterial DNA. Here the authors show that β-lactam antibiotics trigger mutagenesis by upregulating the stress-response protein RpoS, which downregulates mismatch-repair activity.
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影响因子：
6.7
作者：
Gullberg E;Cao S;Berg OG;Ilbäck C;Sandegren L;Hughes D;Andersson DI
通讯作者：
Andersson DI
影响因子：
16
作者：
Kohanski MA;DePristo MA;Collins JJ
通讯作者：
Collins JJ
影响因子：
14.9
作者：
Fröhlich KS;Papenfort K;Berger AA;Vogel J
通讯作者：
Vogel J
影响因子：
64.8
作者：
Jarosz, DF;Godoy, VG;Walker, GC
通讯作者：
Walker, GC
影响因子：
64.5
作者：
Kohanski, Michael A.;Dwyer, Daniel J.;Collins, James J.
通讯作者：
Collins, James J.