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

Abstract

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 1µM 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 1µM 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.