title: Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella.
abstract: The mammalian intestine is host to a microbial community that prevents pathogen expansion through unknown mechanisms, while antibiotic treatment can increase susceptibility to enteric pathogens. Here we show that streptomycin treatment depleted commensal, butyrate-producing Clostridia from the mouse intestinal lumen, leading to decreased butyrate levels, increased epithelial oxygenation, and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by tributyrin treatment. Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission. We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Rivera-Chávez
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Lillian F
authors.initials: LF
authors.lastname: Zhang
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Franziska
authors.initials: F
authors.lastname: Faber
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lopez
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Mariana X
authors.initials: MX
authors.lastname: Byndloss
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Olsan
authors.affiliation: Department of Chemistry, College of Letters and Sciences, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Gege
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Velazquez
authors.affiliation: Department of Chemistry, College of Letters and Sciences, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: ajbaumler@ucdavis.edu.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000332:Aerobiosis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D020148:Butyric Acid / Q000378:metabolism*; D003013:Clostridium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010100:Oxygen / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D013307:Streptomycin / Q000494:pharmacology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D037521:Virulence Factors; D020148:Butyric Acid; D010100:Oxygen; D013307:Streptomycin