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  • 标题:Antibiotic treatment enhances the genome-wide mutation rate of target cells
  • 本地全文:下载
  • 作者:Hongan Long ; Samuel F. Miller ; Chloe Strauss
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2016
  • 卷号:113
  • 期号:18
  • 页码:E2498-E2505
  • DOI:10.1073/pnas.1601208113
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 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.
  • 关键词:antibiotic resistance ; mutation rate ; resistance evolution ; DNA repair ; low-fidelity polymerases
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