TY - JOUR
T1 - An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate
AU - Spiga, Luisella
AU - Winter, Maria G.
AU - Furtado de Carvalho, Tatiane
AU - Zhu, Wenhan
AU - Hughes, Elizabeth R.
AU - Gillis, Caroline C.
AU - Behrendt, Cassie L.
AU - Kim, Jiwoong
AU - Chessa, Daniela
AU - Andrews-Polymenis, Helene L.
AU - Beiting, Daniel P.
AU - Santos, Renato L.
AU - Hooper, Lora V.
AU - Winter, Sebastian E.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/9/13
Y1 - 2017/9/13
N2 - 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.
AB - 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.
KW - Salmonella
KW - bacterial metabolism
KW - gut microbiota
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U2 - 10.1016/j.chom.2017.07.018
DO - 10.1016/j.chom.2017.07.018
M3 - Article
C2 - 28844888
AN - SCOPUS:85028085286
SN - 1931-3128
VL - 22
SP - 291-301.e6
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -