Commensal Klebsiella oxytoca cooperates with other gut bacteria to promote clearance of multi-drug resistant Klebsiella. Commensal Klebsiella oxytoca

Gut colonization with multi-drug resistant (MDR) bacteria enhances the risk of blood-stream infections in susceptible individuals, yet, no clinically effective strategies to promote gut decolonization exist. We observed highly-variable degrees of ex vivo colonization resistance against a carbapenem-resistant Klebsiella pneumoniae strain in human feces samples and isolated from two particularly protected donors commensal Klebsiella oxytoca strains. These strains promoted gut decolonization of MDR K. pneumoniae strains from two sequence types in mouse models. Moreover, K. oxytoca significantly reduced systemic spread of K. pneumoniae in antibiotic-treated mice and antibiotic-naïve gnotobiotic mice. Experiments using germfree and gnotobiotic mice demonstrate that cooperation with other commensal bacteria is required for effective clearance of K. pneumoniae by K. oxytoca suggesting that complex metabolic competition contributes to gut decolonization. Finally, K. oxytoca also protects humanized microbiota mice from susceptible donors against K. pneumoniae colonization demonstrating the potential of commensal K. oxytoca strains as next-generation probiotic.

多重耐药（multi-drug resistant, MDR）细菌定植于肠道，会增加易感个体发生血流感染的风险，但目前尚无临床有效的肠道去定植策略。我们在人类粪便样本中观测到，针对一株碳青霉烯耐药肺炎克雷伯菌（carbapenem-resistant Klebsiella pneumoniae）的体外定植抵抗能力存在显著异质性，并从两名特殊受保护的供体中分离得到了共生产酸克雷伯菌（Klebsiella oxytoca）菌株。该类菌株在小鼠模型中可促进两类序列型的多重耐药肺炎克雷伯菌实现肠道去定植。此外，产酸克雷伯菌可显著降低经抗生素处理小鼠以及未使用过抗生素的悉生小鼠（gnotobiotic mice）体内肺炎克雷伯菌的全身播散程度。利用无菌小鼠（germfree mice）和悉生小鼠开展的实验表明，产酸克雷伯菌要有效清除肺炎克雷伯菌，需与其他共生细菌协同作用，这提示复杂的代谢竞争参与了肠道去定植过程。最后，产酸克雷伯菌还可保护取自易感供体的菌群人源化小鼠（humanized microbiota mice）免受肺炎克雷伯菌定植，证明了共生产酸克雷伯菌菌株作为下一代益生菌（next-generation probiotic）的应用潜力。