OxyR and SoxRS regulation of fur

• Published in: Journal of bacteriology 1999-08, Vol.181 (15), p.4639-4643
• Main Authors: Zheng, M, Doan, B, Schneider, T D, Storz, G
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Base Sequence; DNA Footprinting; DNA-Binding Proteins; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli - physiology; Escherichia coli Proteins; Flavoproteins; fldA gene; fldA protein; Fur gene; Fur protein; Gene Expression Regulation, Bacterial; Genes; Genetics and Molecular Biology; Hydrogen Peroxide - metabolism; Iron; Iron - metabolism; Metabolism; Metalloproteins - metabolism; Molecular Sequence Data; Oxidative Stress; OxyR protein; Paraquat - pharmacology; Promoter Regions, Genetic; Repressor Proteins - genetics; Repressor Proteins - metabolism; Ribonucleic acid; RNA; RNA, Messenger - genetics; SoxRS protein; superoxide; Superoxides - metabolism; Trans-Activators; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - drug effects
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.181.15.4639-4643.1999

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 DeltaoxyR 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 DeltasoxRS strain, and SoxS was shown to bind to the fldA promoter. These results demonstrate that iron metabolism is coordinately regulated with the oxidative stress defenses.