The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. oxytoca species complex strains can produce enterotoxins, namely, tilimycin and tilivalline, while also contributing to colonization resistance (CR). 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 K. oxytoca provides CR against Salmonella Typhimurium. In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against Salmonella 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 K. oxytoca and Salmonella.

产酸克雷伯氏菌复合体是人类微生物组的一部分，尤其是在婴儿期和儿童期。产酸克雷伯菌复杂菌株可以产生肠毒素，即替利霉素和替利缬林，同时也有助于定植抗性（CR）。这些看似矛盾的角色之间的关系尚不清楚。在这里，通过将离体测定与 CRISPR 诱变和各种小鼠模型相结合，我们表明产酸克雷伯菌对鼠伤寒沙门氏菌具有 CR 作用。在体外，针对各种沙门氏菌菌株的抗菌活性取决于替利霉素的产生，并由各种简单碳水化合物诱导。在体内，针对沙门氏菌的CR 取决于无菌小鼠中的毒素产生，而在有残留微生物群的小鼠中则很大程度上不依赖于毒素。这与体内诱导毒素的碳水化合物的相对水平有关。最后，卫矛醇的利用对于无菌小鼠的毒素非依赖性 CR 至关重要。总之，这表明营养物质的可用性是产酸克雷伯菌和沙门氏菌之间毒素依赖性和底物驱动竞争的关键。