The periplasmic nitrate reductase NapABC supports luminal growth of Salmonella enterica serovar typhimurium during colitis

Christopher A. Lopez, Fabian Rivera-Chávez, Mariana X. Byndloss, Andreas J Baumler

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The food-borne pathogen Salmonella enterica serovar Typhimurium benefits from acute inflammation in part by using hostderived nitrate to respire anaerobically and compete successfully with the commensal microbes during growth in the intestinal lumen. The S. Typhimurium genome contains three nitrate reductases, encoded by the narGHI, narZYV, and napABC genes. Work on homologous genes present in Escherichia coli suggests that nitrate reductase A, encoded by the narGHI genes, is the main enzyme promoting growth on nitrate as an electron acceptor in anaerobic environments. Using a mouse colitis model, we found, surprisingly, that S. Typhimurium strains with defects in either nitrate reductase A (narG mutant) or the regulator inducing its transcription in the presence of high concentrations of nitrate (narL mutant) exhibited growth comparable to that of wild-type S. Typhimurium. In contrast, a strain lacking a functional periplasmic nitrate reductase (napA mutant) exhibited a marked growth defect in the lumen of the colon. In E. coli, the napABC genes are transcribed maximally under anaerobic growth conditions in the presence of low nitrate concentrations. Inactivation of narP, encoding a response regulator that activates napABC transcription in response to low nitrate concentrations, significantly reduced the growth of S. Typhimurium in the gut lumen. Cecal nitrate measurements suggested that the murine cecum is a nitrate-limited environment. Collectively, our results suggest that S. Typhimurium uses the periplasmic nitrate reductase to support its growth on the low nitrate concentrations encountered in the gut, a strategy that may be shared with other enteric pathogens.

Original languageEnglish (US)
Pages (from-to)3470-3478
Number of pages9
JournalInfection and Immunity
Volume83
Issue number9
DOIs
StatePublished - 2015

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Nitrate Reductase
Salmonella enterica
Colitis
Nitrates
Growth
Genes
Nitrate Reductases
Escherichia coli
Cecum
Serogroup
Colon
Genome
Electrons
Inflammation
Food
Enzymes

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

The periplasmic nitrate reductase NapABC supports luminal growth of Salmonella enterica serovar typhimurium during colitis. / Lopez, Christopher A.; Rivera-Chávez, Fabian; Byndloss, Mariana X.; Baumler, Andreas J.

In: Infection and Immunity, Vol. 83, No. 9, 2015, p. 3470-3478.

Research output: Contribution to journalArticle

Lopez, Christopher A. ; Rivera-Chávez, Fabian ; Byndloss, Mariana X. ; Baumler, Andreas J. / The periplasmic nitrate reductase NapABC supports luminal growth of Salmonella enterica serovar typhimurium during colitis. In: Infection and Immunity. 2015 ; Vol. 83, No. 9. pp. 3470-3478.
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