Redox sensor SsrB Cys203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection

Maroof Husain, Jessica Jones-Carson, Miryoung Song, Bruce D. McCollister, Travis J. Bourret, Andrés Vázquez-Torres

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We show herein that the Salmonella pathogenicity island 2 (SPI2) response regulator SsrB undergoes S-nitrosylation upon exposure of Salmonella to acidified nitrite, a signal encountered by this enteropathogen in phagosomes of macrophages. Mutational analysis has identified Cys203 in the C-terminal dimerization domain of SsrB as the redox-active residue responding to nitric oxide (NO) congeners generated in the acidification of nitrite. Peroxynitrite and products of the autooxidation of NO in the presence of oxygen, but not hydrogen peroxide, inhibit the DNA-binding capacity of SsrB, demonstrating the selectivity of the reaction of Cys203 with reactive nitrogen species (RNS). These findings identify the two-component response regulator SsrB Cys203 as a thiol-based redox sensor. A C203S substitution protects SsrB against the attack of RNS while preserving its DNA-binding capacity. When exposed to SPI2-inducing conditions, Salmonella expressing the wild-type ssrB allele or the ssrB C203S variant sustain transcription of the sifA, sspH2, and srfJ effector genes. Nonetheless, compared with the strain expressing a redox-resistant SsrB C203S variant, wild-type Salmonella bearing the NO-responsive allele exhibit increased fitness when exposed to RNS in an NRAMPR, C3H/HeN murine model of acute oral infection. Given the widespread occurrence of the wild-type allele in Salmonella enterica, these findings indicate that SsrB Cys203 increases Salmonella virulence by serving as a redox sensor of NO resulting from the host immune response to oral infection.

Original languageEnglish
Pages (from-to)14396-14401
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
StatePublished - Aug 10 2010
Externally publishedYes

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Salmonella
Oxidation-Reduction
Nitric Oxide
Reactive Nitrogen Species
Infection
Genomic Islands
Alleles
Nitrites
Phagosomes
Peroxynitrous Acid
Salmonella enterica
DNA
Dimerization
Sulfhydryl Compounds
Hydrogen Peroxide
Virulence
Macrophages
Oxygen
Genes

All Science Journal Classification (ASJC) codes

  • General

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Redox sensor SsrB Cys203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection. / Husain, Maroof; Jones-Carson, Jessica; Song, Miryoung; McCollister, Bruce D.; Bourret, Travis J.; Vázquez-Torres, Andrés.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 32, 10.08.2010, p. 14396-14401.

Research output: Contribution to journalArticle

Husain, Maroof ; Jones-Carson, Jessica ; Song, Miryoung ; McCollister, Bruce D. ; Bourret, Travis J. ; Vázquez-Torres, Andrés. / Redox sensor SsrB Cys203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 32. pp. 14396-14401.
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