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The relationship between these seemingly contradictory roles is not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis and various mouse models, we show that <jats:italic>K. oxytoca<\/jats:italic> provides CR against <jats:italic>Salmonella<\/jats:italic> Typhimurium. In vitro, the antimicrobial activity against various <jats:italic>Salmonella<\/jats:italic> strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against <jats:italic>Salmonella<\/jats:italic> depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. This was linked to the relative levels of toxin-inducing carbohydrates in vivo. Finally, dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice. Together, this demonstrates that nutrient availability is key to both toxin-dependent and substrate-driven competition between <jats:italic>K. oxytoca<\/jats:italic> and <jats:italic>Salmonella<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/s41564-024-01710-0","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T10:04:01Z","timestamp":1718100241000},"page":"1792-1811","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-650X","authenticated-orcid":false,"given":"Lisa","family":"Osbelt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-5478","authenticated-orcid":false,"given":"\u00c9va d. 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