title: Role of the Salmonella enterica serovar Typhi Fur regulator and small RNAs RfrA and RfrB in iron homeostasis and interaction with host cells.
abstract: Iron is an essential element but can be toxic at high concentrations. Therefore, its acquisition and storage require tight control. Salmonella encodes the global regulator Fur (ferric uptake regulator) and the small regulatory non-coding RNAs (sRNAs) RfrA and RfrB, homologues of RyhB. The role of these iron homeostasis regulators was investigated in Salmonella enterica serovar Typhi (S. Typhi). Strains containing either single or combined deletions of these regulators were obtained. The mutants were tested for growth in low and high iron conditions, resistance to oxidative stress, expression and production of siderophores, and during interaction with host cells. The fur mutant showed a growth defect and was sensitive to hydrogen peroxide. The expression of the sRNAs was responsible for these defects. Siderophore expression by S. Typhi and both sRNAs were regulated by iron and by Fur. Fur contributed to invasion of epithelial cells, and was shown for the first time to play a role in phagocytosis and intracellular survival of S. Typhi in human macrophages. The sRNAs RfrA and RfrB were not required for interaction with epithelial cells, but both sRNAs were important for optimal intracellular replication in macrophages. In S. Typhi, Fur is a repressor of both sRNAs, and loss of either RfrA or RfrB resulted in distinct phenotypes, suggesting a non-redundant role for these regulatory RNAs.
authors.affiliation: Department of Microbiology and Immunology, University of Montreal, C.P. 6128 Succursale Centre-Ville, Montreal, QC H3C 3J7, Canada.
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Leclerc
authors.affiliation: INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC H7V 1B7, Canada.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Dozois
authors.affiliation: Department of Microbiology and Immunology, University of Montreal, C.P. 6128 Succursale Centre-Ville, Montreal, QC H3C 3J7, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Daigle
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D050296:Microbial Viability; D010587:Phagocytosis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012485:Salmonella typhi / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron