Submicromolar hydrogen peroxide disrupts the ability of fur protein to control free-iron levels in Escherichia coli

Shery Varghese, Amy Wu, Sunny Park, Karin R.C. Imlay, James A. Imlay

Research output: Contribution to journalArticlepeer-review


In aerobic environments, mutants of Escherichia coli that lack peroxidase and catalase activities (Hpx-) accumulate submicromolar concentrations of intracellular H2O2. We observed that in defined medium these strains constitutively expressed members of the Fur regulon. Iron-import proteins, which Fur normally represses, were fully induced. H2O2 may antagonize Fur function by oxidizing the Fur:Fe2+ complex and inactivating its repressor function. This is a potential problem, as in iron-rich environments excessive iron uptake would endanger H2O2-stressed cells by accelerating hydroxyl-radical production through the Fenton reaction. However, the OxyR H2O2-response system restored Fur repression in iron-replete Luria-Bertani medium by upregulating the synthesis of Fur protein. Indeed, when the OxyR binding site upstream of fur was disrupted, Hpx- mutants failed to repress transporter synthesis, and they exhibited high levels of intracellular free iron. Mutagenesis and bacteriostasis resulted. These defects were eliminated by mutations or chelators that slowed iron import, confirming that dysregulation of iron uptake was the root problem. Thus, aerobic organisms must grapple with a conundrum: how to monitor iron levels in oxidizing environments that might perturb the valence of the analyte. The induction of Fur synthesis by the OxyR response comprises one evolutionary solution to that problem.

Original languageEnglish (US)
Pages (from-to)822-830
Number of pages9
JournalMolecular Microbiology
Issue number3
StatePublished - May 2007

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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