The YaaA protein of the Escherichia coli OxyR regulon lessens hydrogen peroxide toxicity by diminishing the amount of intracellular unincorporated iron

Yuanyuan Liu, Sarah C. Bauer, James A. Imlay

Research output: Contribution to journalArticlepeer-review

Abstract

Hydrogen peroxide (H2O2) is commonly formed in microbial habitats by either chemical oxidation processes or host defense responses. H2O2 can penetrate membranes and damage key intracellular biomolecules, including DNA and iron-dependent enzymes. Bacteria defend themselves against this H2O2 by inducing a regulon that engages multiple defensive strategies. A previous microarray study suggested that yaaA, an uncharacterized gene found in many bacteria, was induced by H2O2 in Escherichia coli as part of its OxyR regulon. Here we confirm that yaaA is a key element of the stress response to H2O2. In a catalase/peroxidasedeficient (Hpx-) background, yaaA deletion mutants grew poorly, filamented extensively, and lost substantial viability when they were cultured in aerobic LB medium. The results from a thyA forward mutagenesis assay and the growth defect of the yaaA deletion in a recombination-deficient (recA56) background indicated that yaaA mutants accumulated high levels of DNA damage. The growth defect of yaaA mutants could be suppressed by either the addition of iron chelators or mutations that slowed iron import, indicating that the DNA damage was caused by the Fenton reaction. Spin-trapping experiments confirmed that Hpx- yaaA cells had a higher hydroxyl radical (HO) level. Electron paramagnetic resonance spectroscopy analysis showed that the proximate cause was an unusually high level of intracellular unincorporated iron. These results demonstrate that during periods of H2O2 stress the induction of YaaA is a critical device to suppress intracellular iron levels; it thereby attenuates the Fenton reaction and the DNA damage that would otherwise result. The molecular mechanism of YaaA action remains unknown.

Original languageEnglish (US)
Pages (from-to)2186-2196
Number of pages11
JournalJournal of bacteriology
Volume193
Issue number9
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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