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Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion

Franziska Faber, Lisa Tran, Mariana X Byndloss

    Nature
    |June 17, 2016
    PubMed

    Insights

    Antibiotic use can lead to Salmonella expansion in the gut. This study reveals that host-driven oxidation of sugars like galactose and glucose fuels this post-antibiotic pathogen growth.

    Area of Science:

    • Microbiology
    • Gut Microbiome Research
    • Infectious Disease Mechanisms

    Background:

    • Gut microbiota alterations are linked to human diseases, but mechanisms remain unclear.
    • Antibiotic use, particularly streptomycin, disrupts gut microbial balance and promotes Salmonella enterica serovar expansion.
    • Previous studies show streptomycin treatment in mice leads to Salmonella expansion, but the precise mechanisms are not fully understood.

    Purpose of the Study:

    • To elucidate the mechanisms by which streptomycin treatment drives the expansion of Salmonella enterica serovar Typhimurium (S. Typhimurium) in the murine gut.
    • To identify host-derived factors that promote pathogen growth after antibiotic perturbation.
    • To investigate the role of carbohydrate oxidation products in post-antibiotic S. Typhimurium expansion.

    Main Methods:

    • Administered streptomycin to mice to disrupt gut microbiota.
    • Measured the expression of inducible nitric oxide synthase (iNOS) in the caecal mucosa.
    • Analyzed the availability of galactarate and glucarate in the murine caecum post-antibiotic treatment.
    • Utilized genetic modification to ablate S. Typhimurium catabolic pathways for galactarate and glucarate.

    Main Results:

    • Streptomycin treatment increased iNOS expression in the caecal mucosa, leading to higher levels of galactarate and glucarate.
    • S. Typhimurium utilized galactarate and glucarate in the gut lumen of streptomycin-treated mice.
    • Genetic deletion of pathways for galactarate and glucarate metabolism significantly reduced S. Typhimurium competitiveness.

    Conclusions:

    • Host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. Typhimurium.
    • Increased availability of galactarate and glucarate, driven by host iNOS expression, supports pathogen growth after antibiotic treatment.
    • This study identifies host carbohydrate oxidation as a key mechanism in post-antibiotic pathogen expansion within the gut ecosystem.

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