Control of redox balance by the stringent response regulatory protein promotes antioxidant defenses of Salmonella

Calvin A. Henard, Travis J. Bourret, Miryoung Song, Andrés Vázquez-Torres

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We report herein a critical role for the stringent response regulatory DnaK suppressor protein (DksA) in the coordination of antioxidant defenses. DksA helps fine-tune the expression of glutathione biosynthetic genes and discrete steps in the pentose phosphate pathway and tricarboxylic acid cycle that are associated with the generation of reducing power. Control of NAD(P)H/NAD(P) + redox balance by DksA fuels downstream antioxidant enzymatic systems in nutritionally starving Salmonella. Conditional expression of the glucose-6-phosphate dehydrogenase-encoding gene zwf, shown here to be under DksA control, increases both the NADPH pool and antioxidant defenses of dksA mutant Salmonella. The DksA-mediated coordination of redox balance boosts the antioxidant defenses of stationary phase bacteria. Not only does DksA increase resistance of Salmonella against hydrogen peroxide (H2O2), but it also promotes fitness of this intracellular pathogen when exposed to oxyradicals produced by the NADPH phagocyte oxidase in an acute model of infection. Given the role of DksA in the adjustment of gene expression in most bacteria undergoing nutritional deprivation, our findings raise the possibility that the control of central metabolic pathways by this regulatory protein maintains redox homeostasis essential for antioxidant defenses in phylogenetically diverse bacterial species.

Original languageEnglish
Pages (from-to)36785-36793
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number47
DOIs
StatePublished - Nov 19 2010
Externally publishedYes

Fingerprint

Salmonella
Oxidation-Reduction
Antioxidants
Proteins
NAD
Bacteria
Pentoses
Pentose Phosphate Pathway
Gene encoding
Citric Acid Cycle
Glucosephosphate Dehydrogenase
NADPH Oxidase
Pathogens
Phagocytes
Metabolic Networks and Pathways
NADP
Gene expression
Hydrogen Peroxide
Genes
Glutathione

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Control of redox balance by the stringent response regulatory protein promotes antioxidant defenses of Salmonella. / Henard, Calvin A.; Bourret, Travis J.; Song, Miryoung; Vázquez-Torres, Andrés.

In: Journal of Biological Chemistry, Vol. 285, No. 47, 19.11.2010, p. 36785-36793.

Research output: Contribution to journalArticle

Henard, Calvin A. ; Bourret, Travis J. ; Song, Miryoung ; Vázquez-Torres, Andrés. / Control of redox balance by the stringent response regulatory protein promotes antioxidant defenses of Salmonella. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 47. pp. 36785-36793.
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