Gut colonization with multidrug-resistant (MDR) bacteria enhances the risk of bloodstream infections in susceptible individuals. We demonstrate highly variable degrees of ex vivo colonization resistance against a carbapenem-resistant Klebsiella pneumoniae strain in human feces samples and subsequently isolate diverse K. oxytoca strains from protected donors. Several of these K. oxytoca strains reduce gut colonization of MDR K. pneumoniae strains in antibiotic-treated and gnotobiotic mouse models. Comparative analysis of K. oxytoca strains coupled with CRISPR-Cas9-mediated deletion of casA, a protein essential for utilization of selected beta-glucosides, identified competition for specific carbohydrates as key in promoting colonization resistance. In addition to direct competition between K. oxytoca and K. pneumoniae, cooperation with additional commensals is required to reestablish full colonization resistance and gut decolonization. Finally, humanized microbiota mice generated from K. pneumoniae-susceptible donors are protected by K. oxytoca administration, demonstrating the potential of commensal K. oxytoca strains as next-generation probiotics.

多重耐药 (MDR) 细菌的肠道定植会增加易感个体的血液感染风险。我们在人类粪便样本中展示了对耐碳青霉烯类肺炎克雷伯菌菌株的高度不同程度的体外定植抗性，并随后从受保护的供体中分离出多种催产杆菌菌株。在抗生素治疗的小鼠模型和无菌小鼠模型中，这些催产杆菌菌株中的一些减少了耐多药肺炎克雷伯菌菌株的肠道定植。K. oxytoca菌株与 CRISPR-Cas9 介导的casA缺失的比较分析，一种对利用选定的β-葡萄糖苷至关重要的蛋白质，确定了对特定碳水化合物的竞争是促进定植抗性的关键。除了催产杆菌和肺炎克雷伯菌之间的直接竞争外，还需要与其他共生体合作以重新建立完全的定植抗性和肠道去定植。最后，从对肺炎克雷伯菌敏感的供体产生的人源化微生物群小鼠受到催产克雷伯菌的保护，证明了共生的催产克菌菌株作为下一代益生菌的潜力。