Antibiotic treatment enhances the genome-wide mutation rate of target cells

文献类型： 外文期刊

第一作者： Long, Hongan

作者： Long, Hongan;Miller, Samuel F.;Strauss, Chloe;Ye, Zhiqiang;Griffin, Katherine;Te, Ronald;Chen, Chi-Chun;Lynch, Michael;Zhao, Chaoxian;Cheng, Lei;Lee, Heewook

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关键词： antibiotic resistance;mutation rate;resistance evolution;DNA repair;low-fidelity polymerases

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.205； 五年影响因子：12.291 ）

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收录情况： SCI

摘要： Although it is well known that microbial populations can respond adaptively to challenges from antibiotics, empirical difficulties in distinguishing the roles of de novo mutation and natural selection have left several issues unresolved. Here, we explore the mutational properties of Escherichia coli exposed to long-term sublethal levels of the antibiotic norfloxacin, using a mutation accumulation design combined with whole-genome sequencing of replicate lines. The genome-wide mutation rate significantly increases with norfloxacin concentration. This response is associated with enhanced expression of error-prone DNA polymerases and may also involve indirect effects of norfloxacin on DNA mismatch and oxidative-damage repair. Moreover, we find that acquisition of antibiotic resistance can be enhanced solely by accelerated mutagenesis, i.e., without direct involvement of selection. Our results suggest that antibiotics may generally enhance the mutation rates of target cells, thereby accelerating the rate of adaptation not only to the antibiotic itself but to additional challenges faced by invasive pathogens.

分类号： N

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