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

Escherichia coli responds to hydrogen peroxide (H 2 O 2 ) by inducing defenses that protect H 2 O 2 -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 H 2 O 2 , and experiments have indicated that they are not necessary for the cell to withstand natural (low-micromolar) concentrations. In this study, we used H 2 O 2 -scavenging mutants to impose controlled doses of H 2 O 2 for extended time. Transcriptomic analysis revealed that in the presence of 1 µM cytoplasmic H 2 O 2 , 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 H 2 O 2 . However, when these mutants were exposed to 1 µM H 2 O 2 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 H 2 O 2 stress also activated the SOS regulon, and when this induction was blocked, cell replication stopped. Collectively, these data indicate that physiological levels of H 2 O 2 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.