An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate

Luisella Spiga, Maria G. Winter, Tatiane Furtado de Carvalho, Wenhan Zhu, Elizabeth R. Hughes, Caroline C. Gillis, Cassie L. Behrendt, Jiwoong Kim, Daniela Chessa, Helene L. Andrews-Polymenis, Daniel P. Beiting, Renato L. Santos, Lora V. Hooper, Sebastian E. Winter

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The mucosal inflammatory response induced by Salmonella serovar Typhimurium creates a favorable niche for this gut pathogen. Conventional wisdom holds that S. Typhimurium undergoes an incomplete tricarboxylic acid (TCA) cycle in the anaerobic mammalian gut. One change during S. Typhimurium-induced inflammation is the production of oxidized compounds by infiltrating neutrophils. We show that inflammation-derived electron acceptors induce a complete, oxidative TCA cycle in S. Typhimurium, allowing the bacteria to compete with the microbiota for colonization. A complete TCA cycle facilitates utilization of the microbiota-derived fermentation product succinate as a carbon source. S. Typhimurium succinate utilization genes contribute to efficient colonization in conventionally raised mice, but provide no growth advantage in germ-free mice. Mono-association of gnotobiotic mice with Bacteroides, a major succinate producer, restores succinate utilization in S. Typhimurium. Thus, oxidative central metabolism enables S. Typhimurium to utilize a variety of carbon sources, including microbiota-derived succinate. Spiga et al. show that during colonization of the intestinal lumen, the enteric pathogen S. Typhimurium performs a complete TCA cycle. This oxidative central metabolism enables S. Typhimurium to utilize the microbiota-derived fermentation product succinate as a nutrient and to compete with the microbiota for colonization of the intestinal tract.

Original languageEnglish (US)
Pages (from-to)291-301.e6
JournalCell Host and Microbe
Volume22
Issue number3
DOIs
StatePublished - Sep 13 2017

Keywords

  • Salmonella
  • bacterial metabolism
  • gut microbiota

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Spiga, L., Winter, M. G., Furtado de Carvalho, T., Zhu, W., Hughes, E. R., Gillis, C. C., Behrendt, C. L., Kim, J., Chessa, D., Andrews-Polymenis, H. L., Beiting, D. P., Santos, R. L., Hooper, L. V., & Winter, S. E. (2017). An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate. Cell Host and Microbe, 22(3), 291-301.e6. https://doi.org/10.1016/j.chom.2017.07.018