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

Escherichia coli responds to hydrogen peroxide (H₂ O₂ ) by inducing defenses that protect H₂ O₂ -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 H₂ O₂ , and experiments have indicated that they are not necessary for the cell to withstand natural (low-micromolar) concentrations. In this study, we used H₂ O₂ -scavenging mutants to impose controlled doses of H₂ O₂ for extended time. Transcriptomic analysis revealed that in the presence of 1 µM cytoplasmic H₂ O₂ , 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 H₂ O₂ . However, when these mutants were exposed to 1 µM H₂ O₂ 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 H₂ O₂ stress also activated the SOS regulon, and when this induction was blocked, cell replication stopped. Collectively, these data indicate that physiological levels of H₂ O₂ 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.