Agricultural origins of a highly-persistent lineage of vancomycin-resistant Enterococcus faecalis in New Zealand

Enterococcus faecalis and Enterococcus faecium are human and animal gut commensals. Vancomycin-resistant enterococci (VRE) are important opportunistic pathogens with limited treatment options. Historically, the glycopeptide antibiotics vancomycin and avoparcin selected for the emergence of vancomycin resistance in human and animal isolates respectively, resulting in global cessation of avoparcin use between 1997 and 2000. To better understand human and animal-associated VRE strains in the post-avoparcin era, we sequenced the genomes of 231 VRE isolates from New Zealand (NZ) (75 human clinical, 156 poultry) cultured between 1998 and 2009. E. faecium lineages and their antibiotic resistance carriage patterns strictly delineated between agricultural and human reservoirs, with bacitracin resistance ubiquitous in poultry but absent in clinical E. faecium strains. In contrast, one E. faecalis lineage (ST108) predominated in both poultry and human isolates in the three years following avoparcin discontinuation. Both phylogenetic and antimicrobial susceptibility (i.e. ubiquitous bacitracin resistance in both poultry and clinical ST108 isolates) analyses suggest an agricultural origin for the ST108 lineage. VRE isolate resistomes were carried on multiple, heterogeneous plasmids. In some isolate genomes, bacitracin, erythromycin, and vancomycin resistance elements were co-localized, indicating multiple potentially-linked selection mechanisms. Importance: Historical antimicrobial use in NZ agriculture has driven the evolution of ST108, a VRE lineage carrying a range of clinically-relevant antimicrobial resistances. The persistence of this lineage in NZ for over a decade indicates that co-selection may be an important stabilizing mechanism for its persistence.