Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion

Franziska Faber, Lisa Tran, Mariana X. Byndloss, Christopher A. Lopez, Eric M. Velazquez, Tobias Kerrinnes, Sean Paul Nuccio, Tamding Wangdi, Oliver Fiehn, Renee M Tsolis, Andreas J Baumler

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)697-699
Number of pages3
JournalNature
Volume534
Issue number7609
StatePublished - Jun 30 2016

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Salmonella enterica
Streptomycin
Anti-Bacterial Agents
Gastroenteritis
Nitric Oxide Synthase Type II
Galactose
Feces
Serogroup
Mucous Membrane
Therapeutics
Carbohydrates
Gene Expression
Glucose
Recurrence
Gastrointestinal Microbiome

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Faber, F., Tran, L., Byndloss, M. X., Lopez, C. A., Velazquez, E. M., Kerrinnes, T., ... Baumler, A. J. (2016). Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion. Nature, 534(7609), 697-699.

Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion. / Faber, Franziska; Tran, Lisa; Byndloss, Mariana X.; Lopez, Christopher A.; Velazquez, Eric M.; Kerrinnes, Tobias; Nuccio, Sean Paul; Wangdi, Tamding; Fiehn, Oliver; Tsolis, Renee M; Baumler, Andreas J.

In: Nature, Vol. 534, No. 7609, 30.06.2016, p. 697-699.

Research output: Contribution to journalArticle

Faber, F, Tran, L, Byndloss, MX, Lopez, CA, Velazquez, EM, Kerrinnes, T, Nuccio, SP, Wangdi, T, Fiehn, O, Tsolis, RM & Baumler, AJ 2016, 'Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion', Nature, vol. 534, no. 7609, pp. 697-699.
Faber F, Tran L, Byndloss MX, Lopez CA, Velazquez EM, Kerrinnes T et al. Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion. Nature. 2016 Jun 30;534(7609):697-699.
Faber, Franziska ; Tran, Lisa ; Byndloss, Mariana X. ; Lopez, Christopher A. ; Velazquez, Eric M. ; Kerrinnes, Tobias ; Nuccio, Sean Paul ; Wangdi, Tamding ; Fiehn, Oliver ; Tsolis, Renee M ; Baumler, Andreas J. / Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion. In: Nature. 2016 ; Vol. 534, No. 7609. pp. 697-699.
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