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

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

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


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 associatedwith 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.

Original languageEnglish (US)
Pages (from-to)E2498-E2505
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - May 3 2016
Externally publishedYes


  • Antibiotic resistance
  • DNA repair
  • Low-fidelity polymerases
  • Mutation rate
  • Resistance evolution

ASJC Scopus subject areas

  • General


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