OxyR and SoxRS Regulation offur

ABSTRACT The cytotoxic effects of reactive oxygen species are largely mediated by iron. Hydrogen peroxide reacts with iron to form the extremely reactive and damaging hydroxyl radical via the Fenton reaction. Superoxide anion accelerates this reaction because the dismutation of superoxide leads to increased levels of hydrogen peroxide and because superoxide elevates the intracellular concentration of iron by attacking iron-sulfur proteins. We found that regulators of the Escherichia coli responses to oxidative stress, OxyR and SoxRS, activate the expression of Fur, the global repressor of ferric ion uptake. A transcript encoding Fur was induced by hydrogen peroxide in a wild-type strain but not in a ΔoxyR strain, and DNase I footprinting assays showed that OxyR binds to the fur promoter. In cells treated with the superoxide-generating compound paraquat, we observed the induction of a longer transcript encompassing both fur and its immediate upstream gene fldA, which encodes a flavodoxin. This polycistronic mRNA is induced by paraquat in a wild-type strain but not in a ΔsoxRS strain, and SoxS was shown to bind to thefldA promoter. These results demonstrate that iron metabolism is coordinately regulated with the oxidative stress defenses.

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