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

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.