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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Husain M,Jones-Carson J,Liu L,Song M,Saah JR,Troxell B,Mendoza M,Hassan H,Vázquez-Torres A

doi

10.1128/IAI.01201-13

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

333-40

issue

1

eissn

0019-9567

issn

1098-5522

pii

IAI.01201-13

journal_volume

82

pub_type

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