title: Regulation of the Salmonella typhimurium flavohemoglobin gene. A new pathway for bacterial gene expression in response to nitric oxide.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Crawford
authors.forename: D E
authors.initials: DE
authors.lastname: Goldberg
mesh_terms: D015082:2,2'-Dipyridyl / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006420:Hemeproteins / Q000096:biosynthesis / Q000235:genetics*; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009589:Nitrogen Oxides; D009603:Nitroso Compounds / Q000494:pharmacology; D009876:Operon; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012097:Repressor Proteins / Q000378:metabolism; D026422:S-Nitrosoglutathione; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D006420:Hemeproteins; D007506:Iron-Sulfur Proteins; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C068477:ferric uptake regulating proteins, bacterial; C086193:flavohemoprotein, Bacteria; C091861:spermine nitric oxide complex; C070725:SoxS protein, E coli; D013096:Spermine; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl; D026422:S-Nitrosoglutathione; D005978:Glutathione