Bacteriocin production facilitates nosocomial emergence of vancomycin-resistant Enterococcus faecium

Gastrointestinal colonization by the nosocomial pathogen vancomycin-resistant Enterococcus faecium (VREfm) can lead to bloodstream infections with high mortality rates. Shifts in VREfm lineages found within healthcare settings occur, but reasons underlying these changes are not understood. Here we sequenced 710 VREfm clinical isolates collected between 2017 and 2022 from a large tertiary care centre. Genomic analyses revealed a polyclonal VREfm population, although 46% of isolates formed genetically related clusters, suggesting a high transmission rate. Comparing these data to a global collection of 15,631 publicly available VREfm genomes collected between 2002 and 2022 identified replacement of the sequence type (ST) 17 VREfm lineage by emergent ST80 and ST117 lineages at the local and global level. Comparative genomic and functional analyses revealed that emergent lineages encoded bacteriocin T8, which conferred a competitive advantage over bacteriocin T8-negative strains in vitro and upon colonization of the mouse gut. Bacteriocin T8 carriage was also strongly associated with strain emergence in the global genome collection. These data suggest that bacteriocin T8-mediated competition may have contributed to VREfm lineage replacement. Genomic and functional analyses of healthcare-associated vancomycin-resistant Enterococcus faecium reveal that bacteriocin T8 is enriched in emergent lineages and provides a competitive advantage in vitro and in vivo.