Letter | Published:

Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion

Nature volume 534, pages 697699 (30 June 2016) | Download Citation


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 serovars1, increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse2,3. 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 bowel4. 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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    et al. Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella. J. Infect. Dis. 161, 255–260 (1990)

  2. 2.

    , , & Treatment of Salmonella gastroenteritis with ampicillin, amoxicillin, or placebo. Pediatrics 65, 1125–1130 (1980)

  3. 3.

    & Effect of antibiotic therapy in acute salmonellosis on the fecal excretion of salmonellae. N. Engl. J. Med. 281, 636–640 (1969)

  4. 4.

    , & Effect of streptomycin on susceptibility of intestinal tract to experimental Salmonella infection. Proc. Soc. Exp. Biol. Med. 86, 132–137 (1954)

  5. 5.

    & Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut. MBio 5, e00929–14 (2014)

  6. 6.

    Kauffmann–White–Schema (1989) 1–171 (Bundesgesundheitsamt, 1992)

  7. 7.

    , , , & Hydrogen-stimulated carbon acquisition and conservation in Salmonella enterica serovar Typhimurium. J. Bacteriol. 193, 5824–5832 (2011)

  8. 8.

    , , & A link between gut community metabolism and pathogenesis: molecular hydrogen-stimulated glucarate catabolism aids Salmonella virulence. Open Biol. 3, 130146 (2013)

  9. 9.

    et al. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect. Immun. 71, 2839–2858 (2003)

  10. 10.

    , , & Contribution of Salmonella typhimurium virulence factors to diarrheal disease in calves. Infect. Immun. 67, 4879–4885 (1999)

  11. 11.

    et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502, 96–99 (2013)

  12. 12.

    et al. Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration. MBio 4, e00430–13 (2013)

  13. 13.

    et al. Comparison of the nitric oxide synthase inhibitors methylarginine and aminoguanidine as prophylactic and therapeutic agents in rat adjuvant arthritis. J. Rheumatol. 22, 1922–1928 (1995)

  14. 14.

    , & Vascular endothelial cells synthesize nitric oxide from l-arginine. Nature 333, 664–666 (1988)

  15. 15.

    The use of TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) for the oxidation of primary and secondary alcohols. Quim. Nova 27, 287–292 (2004)

  16. 16.

    & Organocatalytic oxidations mediated by nitroxyl radicals. Adv. Synth. Catal. 346, 1051–1071 (2004)

  17. 17.

    & Ecological mechanism controlling growth of Escherichia coli in continuous flow cultures and in the mouse intestine. J. Infect. Dis. 114, 235–242 (1964)

  18. 18.

    et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nature Commun . 5, 3114 (2014)

  19. 19.

    et al. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity. FASEB J. 29, 2397–2411 (2015)

  20. 20.

    & Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control. J. Intern. Med. 277, 501–512 (2015)

  21. 21.

    & MudSacI, a transposon with strong selectable and counterselectable markers: use for rapid mapping of chromosomal mutations in Salmonella typhimurium. J. Bacteriol. 177, 1383–1387 (1995)

  22. 22.

    et al. Contribution of flagellin pattern recognition to intestinal inflammation during Salmonella enterica serotype Typhimurium infection. Infect. Immun. 77, 1904–1916 (2009)

  23. 23.

    et al. Quality control for plant metabolomics: reporting MSI-compliant studies. Plant J. 53, 691–704 (2008)

  24. 24.

    et al. Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917. J. Bacteriol. 186, 5432–5441 (2004)

  25. 25.

    , & Ethanolamine utilization in Salmonella typhimurium: nucleotide sequence, protein expression, and mutational analysis of the cchA cchB eutE eutJ eutG eutH gene cluster. J. Bacteriol. 177, 1357–1366 (1995)

  26. 26.

    , & A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc. Natl Acad. Sci. USA 86, 5054–5058 (1989)

  27. 27.

    et al. Salmonella uses energy taxis to benefit from intestinal inflammation. PLoS Pathog. 9, e1003267 (2013)

  28. 28.

    et al. Molecular and phenotypic analysis of the CS54 island of Salmonella enterica serotype Typhimurium: identification of intestinal colonization and persistence determinants. Infect. Immun. 71, 629–640 (2003)

  29. 29.

    et al. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5, 476–486 (2009)

  30. 30.

    et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 339, 708–711 (2013)

Download references


This work was supported by Public Health Service grants OD010931 (E.M.V.), AI060555 (S.-P.N.), AI096528 (A.J.B.), AI109799 (R.M.T), AI112241 (C.A.L.), AI112258 (R.M.T), AI112445 (A.J.B.), U24 DK097154 (O.F.), AI112949 (A.J.B.) and AI114922 (A.J.B.).

Author information


  1. Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, California 95616, USA

    • Franziska Faber
    • , Lisa Tran
    • , Mariana X. Byndloss
    • , Christopher A. Lopez
    • , Eric M. Velazquez
    • , Tobias Kerrinnes
    • , Sean-Paul Nuccio
    • , Tamding Wangdi
    • , Renée M. Tsolis
    •  & Andreas J. Bäumler
  2. Genome Center, University of California at Davis, One Shields Avenue, Davis, California 95616, USA

    • Oliver Fiehn
  3. King Abdulaziz University, Biochemistry Department, Jeddah 21412, Saudi Arabia

    • Oliver Fiehn


  1. Search for Franziska Faber in:

  2. Search for Lisa Tran in:

  3. Search for Mariana X. Byndloss in:

  4. Search for Christopher A. Lopez in:

  5. Search for Eric M. Velazquez in:

  6. Search for Tobias Kerrinnes in:

  7. Search for Sean-Paul Nuccio in:

  8. Search for Tamding Wangdi in:

  9. Search for Oliver Fiehn in:

  10. Search for Renée M. Tsolis in:

  11. Search for Andreas J. Bäumler in:


F.F. performed bacterial growth assays, most animal experiments and analysed the results. O.F. performed GC/MS measurements. M.X.B. scored histological sections. A.J.B., L.T., C.A.L., E.M.V., T.K. and T.W. assisted with animal experiments. F.F., S.-P.N., R.M.T. and A.J.B. were responsible for the overall study design. F.F. and A.J.B. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andreas J. Bäumler.

Reviewer Information Nature thanks D. Bolam, D. Bumann, M. Fischbach & D. M. Monack for their contribution to the peer review of this work.

Extended data

About this article

Publication history






Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.