Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium

Antibiotic-mediated microbiota destruction and the consequent loss of colonization resistance can result in intestinal domination with vancomycin-resistant Enterococcus (VRE), leading to bloodstream infection in hospitalized patients. Clearance of VRE remains a challenging goal that, if achieved, would reduce systemic VRE infections and patient-to-patient transmission. Although obligate anaerobic commensal bacteria have been associated with colonization resistance to VRE, the specific bacterial species involved remain undefined. Herein, we demonstrate that a precisely defined consortium of commensal bacteria containing the Clostridium cluster XIVa species Blautia producta and Clostridium bolteae restores colonization resistance against VRE and clears VRE from the intestines of mice. While C. bolteae did not directly mediate VRE clearance, it enabled intestinal colonization with B. producta, which directly inhibited VRE growth. These findings suggest that therapeutic or prophylactic administration of defined bacterial consortia to individuals with compromised microbiota composition may reduce inter-patient transmission and intra-patient dissemination of highly antibiotic-resistant pathogens. [Display omitted] •Microbiota damage and VRE infection are corrected by fecal transplantation•Fecal fractionation identified four commensal species that prevent VRE infection•Colonization resistance against VRE requires commensal bacterial cooperation Vancomycin-resistant Enterococcus (VRE) can densely colonize intestines and cause bloodstream infections. The intestinal microbiota provides resistance against VRE colonization. Caballero and colleagues demonstrate in mice that Blautia producta and Clostridium bolteae restore resistance against VRE. Administration of specific consortia of commensal bacteria can re-establish colonization resistance against highly antibiotic-resistant pathogens.