Escherichia coli induces DNA repair enzymes to protect itself from low-grade hydrogen peroxide stress

Anshika Gupta, James A. Imlay

Research output: Contribution to journalArticlepeer-review

Abstract

Escherichia coli responds to hydrogen peroxide (H2O2) by inducing defenses that protect H2O2-sensitive enzymes. DNA is believed to be another important target of oxidation, and E. coli contains enzymes that can repair oxidative lesions in vitro. However, those enzymes are not known to be induced by H2O2, and experiments have indicated that they are not necessary for the cell to withstand natural (low-micromolar) concentrations. In this study, we used H2O2-scavenging mutants to impose controlled doses of H2O2 for extended time. Transcriptomic analysis revealed that in the presence of 1 µM cytoplasmic H2O2, the OxyR transcription factor-induced xthA, encoding exonuclease III. The xthA mutants survived a conventional 15-min exposure to even 100 times this level of H2O2. However, when these mutants were exposed to 1 µM H2O2 for hours, they accumulated DNA lesions, failed to propagate, and eventually died. Although endonuclease III (nth) was not induced, nth mutants struggled to grow. Low-grade H2O2 stress also activated the SOS regulon, and when this induction was blocked, cell replication stopped. Collectively, these data indicate that physiological levels of H2O2 are a real threat to DNA, and the engagement of the base-excision-repair and SOS systems is necessary to enable propagation during protracted stress.

Original languageEnglish (US)
Pages (from-to)754-769
Number of pages16
JournalMolecular Microbiology
Volume117
Issue number4
DOIs
StatePublished - Apr 2022

Keywords

  • DNA damage
  • Fenton reaction
  • oxidative stress

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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