Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion.
Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars, increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse. These antibiotic-induced changes in the gut microbiota can be studied in mice, in which the disruption of a balanced microbial community by treatment with the antibiotic streptomycin leads to an expansion of S. enterica serovars in the large bowel. However, the mechanisms by which streptomycin treatment drives an expansion of S. enterica serovars are not fully resolved. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovar Typhimurium (S. Typhimurium). By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the caecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine caecum. S. Typhimurium used galactarate and glucarate within the gut lumen of streptomycin pre-treated mice, and genetic ablation of the respective catabolic pathways reduced S. Typhimurium competitiveness. Our results identify host-mediated oxidation of carbohydrates in the gut as a mechanism for post-antibiotic pathogen expansion.
Franziska
F
Faber
Lisa
L
Tran
Mariana X
MX
Byndloss
Christopher A
CA
Lopez
Eric M
EM
Velazquez
Tobias
T
Kerrinnes
Sean-Paul
SP
Nuccio
Tamding
T
Wangdi
Oliver
O
Fiehn
Renée M
RM
Tsolis
Andreas J
AJ
Bäumler
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000235:genetics; D002432:Cecum / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology; D005260:Female; D005690:Galactose / Q000378:metabolism; D005759:Gastroenteritis / Q000382:microbiology; D005937:Glucaric Acid / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009876:Operon / Q000235:genetics; D010084:Oxidation-Reduction / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D013307:Streptomycin / Q000494:pharmacology*; D013400:Sugar Acids / Q000378:metabolism
D000900:Anti-Bacterial Agents; D026361:Reactive Nitrogen Species; D013400:Sugar Acids; C000090:galactaric acid; D052247:Nitric Oxide Synthase Type II; D005947:Glucose; D005937:Glucaric Acid; D005690:Galactose; D013307:Streptomycin