Details

Autor(en) / Beteiligte

• Rivera-Chávez, Fabian
• Zhang, Lillian F.
• Faber, Franziska
• Lopez, Christopher A.
• Byndloss, Mariana X.
• Olsan, Erin E.
• Xu, Gege
• Velazquez, Eric M.
• Lebrilla, Carlito B.
• Winter, Sebastian E.
• Bäumler, Andreas J.

Titel

Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella

Ist Teil von

• Cell host & microbe, 2016-04, Vol.19 (4), p.443-454

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Salmonella-induced colitis drives a depletion of butyrate-producing Clostridia•Antibiotic-mediated depletion of Clostridia increases colonocyte oxygenation•Increased epithelial oxygenation drives an aerobic post-antibiotic pathogen expansion•A respiration-driven Salmonella expansion in the gut is required for transmission Paradoxically, antibiotic treatment can promote relapse of Salmonella gastroenteritis. Rivera-Chávez et al. show that antibiotic treatment lowers colonization resistance by depleting butyrate-producing Clostridia. Decreased butyrate availability increases epithelial oxygenation, thereby fueling aerobic pathogen expansion in the gut lumen. Aerobic respiration synergizes with nitrate respiration to drive fecal-oral transmission of Salmonella.