Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses

Travis J. Bourret, Steffen Porwollik, Michael McClelland, Rui Zhao, Todd Greco, Harry Ischiropoulos, Andrés Vázquez-Torres

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Reactive nitrogen species (RNS) derived from dietary and salivary inorganic nitrogen oxides foment innate host defenses associated with the acidity of the stamach. The mechanisms by which these reactive species exert antimicrobial activity in the gastric lumen are, however, poorly understood. Methodology/Principal Findings: The genetically tractable acid tolerance response (ATR) that enables enteropathogens to survive harsh acidity was screened for signaling pathways responsive to RNS. The nitric oxide (NO) donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely repressed oral virulence as demonstrated by the fact that Salmonella bacteria exposed to NO donors during mildly acidic conditions were shed in low amounts in feces and exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, suggesting that RNS target regulatory cascades but not their effectors. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment. Conclusions/Significance: Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of innate host defenses.

Original languageEnglish
Article numbere1833
JournalPLoS One
Volume3
Issue number3
DOIs
StatePublished - Mar 19 2008
Externally publishedYes

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Reactive Nitrogen Species
acid tolerance
Salmonella
nitric oxide
Stomach
Nitric Oxide
stomach
Acids
nitrogen
Nitric Oxide Donors
Acidity
fur
acidity
mouth
Bacteria
virulence
Acid resistance
Nitrogen Oxides
enteropathogens
Virulence

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bourret, T. J., Porwollik, S., McClelland, M., Zhao, R., Greco, T., Ischiropoulos, H., & Vázquez-Torres, A. (2008). Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses. PLoS One, 3(3), [e1833]. https://doi.org/10.1371/journal.pone.0001833

Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses. / Bourret, Travis J.; Porwollik, Steffen; McClelland, Michael; Zhao, Rui; Greco, Todd; Ischiropoulos, Harry; Vázquez-Torres, Andrés.

In: PLoS One, Vol. 3, No. 3, e1833, 19.03.2008.

Research output: Contribution to journalArticle

Bourret, TJ, Porwollik, S, McClelland, M, Zhao, R, Greco, T, Ischiropoulos, H & Vázquez-Torres, A 2008, 'Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses', PLoS One, vol. 3, no. 3, e1833. https://doi.org/10.1371/journal.pone.0001833
Bourret, Travis J. ; Porwollik, Steffen ; McClelland, Michael ; Zhao, Rui ; Greco, Todd ; Ischiropoulos, Harry ; Vázquez-Torres, Andrés. / Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses. In: PLoS One. 2008 ; Vol. 3, No. 3.
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