Journal of Bacteriology, August 1999, p. 4639-4643, Vol. 181, No. 15
0021-9193/99/$04.00+0
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892,1 and Laboratory of Experimental and Computational Biology, National Cancer Institute, Frederick, Maryland 217022
Received 9 April 1999/Accepted 21 May 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
oxyR 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
soxRS 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.
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