OxyR and SoxRS regulation of fur

The cytotoxic effects of reactive oxygen species are largely mediated by ir on. Hydrogen peroxide reacts with iron to form the extremely reactive and d amaging hydroxyl radical via the Fenton reaction. Superoxide anion accelera tes this reaction because the dismutation of superoxide leads to increased levels of hydrogen peroxide and because superoxide elevates the intracellul ar concentration of iron by attacking iron-sulfur proteins. We found that r egulators of the Escherichia coli responses to oxidative stress, OxyR and S oxRS, activate the expression of Fur, the global repressor of ferric ion up take. A transcript encoding Fur was induced by hydrogen peroxide in a wild- type strain but not in a Delta oxyR strain, and DNase I footprinting assays showed that OxyR binds to the fur promoter. In cells treated with the supe roxide-generating compound paraquat, we observed the induction of a longer transcript encompassing both fur and its immediate upstream gene fldA, whic h encodes a flavodoxin. This polycistronic mRNA is induced by paraquat in a wild-type strain but not in a Delta soxRS strain, and SoxS was shown to bi nd to the fldA promoter. These results demonstrate that iron metabolism is coordinately regulated with the oxidative stress defenses.