An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate.
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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, L., Winter, M. G., Furtado de Carvalho, T., Zhu, W., Hughes, E. R., Gillis, C. C., ... Winter, S. E.
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Spiga, Luisella||Winter, Maria G||Furtado de Carvalho, Tatiane||Zhu, Wenhan||Hughes, Elizabeth R||Gillis, Caroline C||Behrendt, Cassie L||Kim, Jiwoong||Chessa, Daniela||Andrews-Polymenis, Helene L||Beiting, Daniel P||Santos, Renato L||Hooper, Lora V||Winter, Sebastian E