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J Biol Chem, Vol. 273, Issue 51, 34028-34032, December 18, 1998

Regulation of the Salmonella typhimurium Flavohemoglobin Gene
A NEW PATHWAY FOR BACTERIAL GENE EXPRESSION IN RESPONSE TO NITRIC OXIDE

From the Howard Hughes Medical Institute, Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110

Flavohemoglobins, a family of two-domain proteins with homology to vertebrate hemoglobins, are found in a variety of prokaryotic and eukaryotic microorganisms. Recent studies suggest a role for these proteins in nitrogen oxide metabolism. We now show that nitric oxide donors positively regulate a chromosomal flavohemoglobin (hmp)/lacZ operon fusion in Salmonella typhimurium. hmp gene expression in the presence of NO^· is independent of the SoxS, OxyR, and FNR transcription factors and instead relies on inactivation of the iron-dependent Fur repressor. Other Fur-repressed promoters in S. typhimurium are also activated by an NO^· donor. In contrast to the wild-type strain, an hmp mutant requires markedly lower concentrations of NO to induce the hmp/lacZ fusion, whereas its response to iron chelation is equivalent to wild type. These data unveil a new pathway for NO-dependent gene expression in S. typhimurium.

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