Salmonella Typhimurium screen identifies shifts in mixed-acid fermentation during gut colonization.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, Mass. : Cell Press
    • Subject Terms:
      Salmonella typhimurium*/growth & development ; Salmonella typhimurium*/genetics ; Salmonella typhimurium*/metabolism ; Fermentation*; Animals ; Mice ; Gastrointestinal Tract/microbiology ; Citric Acid Cycle ; Mice, Inbred C57BL ; Acetates/metabolism ; DNA Transposable Elements ; Germ-Free Life ; Gastrointestinal Microbiome/physiology ; Ethanol/metabolism ; Gluconeogenesis ; Fumarates/metabolism ; Mutagenesis
    • Abstract:
      How enteric pathogens adapt their metabolism to a dynamic gut environment is not yet fully understood. To investigate how Salmonella enterica Typhimurium (S.Tm) colonizes the gut, we conducted an in vivo transposon mutagenesis screen in a gnotobiotic mouse model. Our data implicate mixed-acid fermentation in efficient gut-luminal growth and energy conservation throughout infection. During initial growth, the pathogen utilizes acetate fermentation and fumarate respiration. After the onset of gut inflammation, hexoses appear to become limiting, as indicated by carbohydrate analytics and the increased need for gluconeogenesis. In response, S.Tm adapts by ramping up ethanol fermentation for redox balancing and supplying the TCA cycle with α-ketoglutarate for additional energy. Our findings illustrate how S.Tm flexibly adapts mixed fermentation and its use of the TCA cycle to thrive in the changing gut environment. Similar metabolic wiring in other pathogenic Enterobacteriaceae may suggest a broadly conserved mechanism for gut colonization.
      Competing Interests: Declaration of interests The authors declare no competing interests.
      (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Salmonella; TCA cycle; central carbon metabolism; glycolysis; infection; inflammation; metabolism; microbiota; mixed-acid fermentation
    • Accession Number:
      0 (Acetates)
      0 (DNA Transposable Elements)
      3K9958V90M (Ethanol)
      0 (Fumarates)
    • Publication Date:
      Date Created: 20240918 Date Completed: 20241010 Latest Revision: 20241011
    • Publication Date:
      20241012
    • Accession Number:
      10.1016/j.chom.2024.08.015
    • Accession Number:
      39293436