![]() Typhimurium wild type in mice that had not received antibiotics. Grey shading indicates average colonization levels of the S. Typhimurium strains by oral gavage and bacteria were recovered from colon contents four days later. ( c) Groups of streptomycin pre-treated or mock-treated (no antibiotic) mice (C57BL/6) received the indicated S. ( a and b) Growth was verified with 3 biological replicates. CI, competitive index recovered after 24-hour incubation in an anaerobe chamber. Typhimurium wild type and the gudT-STM2959 mutant. ( b) Minimal medium or mucin broth supplemented with the indicated carbon sources (0.1 % w/v) was inoculated with a 1:1 mixture of the S. Typhimurium strains to ferment the indicated monosaccharides was detected using a pH indicator. The operon for galactarate utilization contributes to post-antibiotic expansion of S. These data suggested that neither the diet nor the mucus naturally contained biologically relevant quantities of a substrate for enzymes encoded by the gudT ygcY gudD STM2959 operon. Typhimurium for anaerobic growth on hog mucin as the sole carbon source, but fitness of the gudT-STM2959 mutant was reduced compared to the wild type when galactarate or glucarate was added to the medium ( Fig. Genetic ablation of galactarate/glucarate utilization did not reduce the fitness of S. Typhimurium unable to ferment galactarate and glucarate, but did not affect its ability to utilize other monosaccharides ( Fig. Deletion of galactarate utilization genes rendered S. ![]() Typhimurium is induced by hydrogen, a fermentation product of the gut microbiota 8. Expression of the gudT ygcY gudD STM2959 operon in S. ![]() 1c), which encodes proteins involved in galactarate uptake and catabolism 7. Typhimurium strain lacking the gudT ygcY gudD STM2959 operon ( gudT-STM2959 mutant, Extended Data Fig. To investigate whether this nutrient is normally available to promote growth in mucus, we constructed a S. We therefore investigated the origin of galactarate in the intestine.Ĭonsistent with the idea that galactarate is a xenobiotic, the concentration of this sugar in mouse chow was very low, as suggested by gas chromatography/mass spectrometry (GC/MS) measurements ( Extended Data Fig. However, the biological significance of this association is not clear, because galactarate is a xenobiotic that is not normally produced by mammals or expected to be present within the diet. While 98.2% of serovars associated with gastrointestinal infections can ferment this carbon source, only 15.4% of serovars associated with extraintestinal disease test positive for this reaction 6 ( Extended Data Fig. Galactarate fermentation is one of the biochemical reactions used to differentiate members of the genus Salmonella into serovars. enterica serovars causing gastrointestinal disease 5. Our results identify a host-mediated oxidation of carbohydrates in the gut as a novel mechanism for post-antibiotic pathogen expansion.Ī recent in silico analysis suggests that pathways involved in galactarate uptake and catabolism are associated with S. Typhimurium utilized galactarate and glucarate within the gut lumen of streptomycin pre-treated mice and genetic ablation of the respective catabolic pathways reduced its competitiveness. By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the cecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine cecum. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovars are not fully resolved. However, the mechanisms by which streptomycin treatment drives an expansion of S. These antibiotic-induced changes in the gut microbiota can be studied in mice, where the disruption of a balanced microbial community by treatment with streptomycin leads to an expansion of S. ![]() Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars 1, increases the duration for which patients shed the pathogen in their feces and may on occasion produce a bacteriologic and symptomatic relapse 2, 3. Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. ![]()
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