title: Fur negatively regulates hns and is required for the expression of HilA and virulence in Salmonella enterica serovar Typhimurium.
abstract: Iron is an essential element for the survival of living cells. However, excess iron is toxic, and its uptake is exquisitely regulated by the ferric uptake regulator, Fur. In Salmonella, the Salmonella pathogenicity island 1 (SPI-1) encodes a type three secretion system, which is required for invasion of host epithelial cells in the small intestine. A major activator of SPI-1 is HilA, which is encoded within SPI-1. One known regulator of hilA is Fur. The mechanism of hilA regulation by Fur is unknown. We report here that Fur is required for virulence in Salmonella enterica serovar Typhimurium and that Fur is required for the activation of hilA, as well as of other HilA-dependent genes, invF and sipC. The Fur-dependent regulation of hilA was independent of PhoP, a known repressor of hilA. Instead, the expression of the gene coding for the histone-like protein, hns, was significantly derepressed in the fur mutant. Indeed, the activation of hilA by Fur was dependent on 28 nucleotides located upstream of hns. Moreover, we used chromatin immunoprecipitation to show that Fur bound, in vivo, to the upstream region of hns in a metal-dependent fashion. Finally, deletion of fur in an hns mutant resulted in Fur-independent activation of hilA. In conclusion, Fur activates hilA by repressing the expression of hns.
authors.affiliation: Department of Microbiology, North Carolina State University, Raleigh, NC 27695-7615, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Troxell
authors.forename: Michael L
authors.initials: ML
authors.lastname: Sikes
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fink
authors.forename: Andres
authors.initials: A
authors.lastname: Vazquez-Torres
authors.forename: Jessica
authors.initials: J
authors.lastname: Jones-Carson
authors.forename: Hosni M
authors.initials: HM
authors.lastname: Hassan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005798:Genes, Bacterial; D044404:Genomic Islands; D051379:Mice; D008809:Mice, Inbred C3H; D009876:Operon; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology*; D016019:Survival Analysis; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C031908:H-NS protein, bacteria; C102236:HilA protein, Salmonella; D012097:Repressor Proteins; C094578:Salmonella invasion protein C; D015534:Trans-Activators; D014157:Transcription Factors; D037521:Virulence Factors; C068477:ferric uptake regulating proteins, bacterial; C090990:invF protein, Salmonella