title: Ferric uptake regulator-dependent antinitrosative defenses in Salmonella enterica serovar Typhimurium pathogenesis.
abstract: Herein we report an important role for the ferric uptake regulator (Fur) in the resistance of Salmonella enterica serovar Typhimurium to the reactive nitrogen species produced by inducible nitric oxide (NO) synthase in an NRAMP1(r) murine model of acute systemic infection. The expression of fur protected Salmonella grown under normoxic and hypoxic conditions against the bacteriostatic activity of NO. The hypersusceptibility of fur-deficient Salmonella to the cytotoxic actions of NO coincides with a marked repression of respiratory activity and the reduced ability of the bacteria to detoxify NO. A fur mutant Salmonella strain contained reduced levels of the terminal quinol oxidases of the electron transport chain. Addition of the heme precursor δ-aminolevulinic acid restored the cytochrome content, respiratory activity, NO consumption, and wild-type growth in bacteria undergoing nitrosative stress. The innate antinitrosative defenses regulated by Fur added to the adaptive response associated with the NO-detoxifying activity of the flavohemoprotein Hmp. Our investigations indicate that, in addition to playing a critical role in iron homeostasis, Fur is an important antinitrosative determinant of Salmonella pathogenesis.
authors.affiliation: Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Maroof
authors.initials: M
authors.lastname: Husain
authors.forename: Jessica
authors.initials: J
authors.lastname: Jones-Carson
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Miryoung
authors.initials: M
authors.lastname: Song
authors.forename: J Royden
authors.initials: JR
authors.lastname: Saah
authors.forename: Bryan
authors.initials: B
authors.lastname: Troxell
authors.forename: Mary
authors.initials: M
authors.lastname: Mendoza
authors.forename: Hosni
authors.initials: H
authors.lastname: Hassan
authors.forename: Andrés
authors.initials: A
authors.lastname: Vázquez-Torres
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D051379:Mice; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000502:physiology; D012097:Repressor Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D012480:Salmonella Infections / Q000382:microbiology* / Q000503:physiopathology; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity*; D013312:Stress, Physiological / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D052247:Nitric Oxide Synthase Type II