Genomics to understand the global landscape of linezolid resistance in Enterococcus faecium and Enterococcus faecalis

Linezolid is an oxazolidinone antibiotic and is a last-line agent for treating infections caused by vancomycin-resistant <i>Enterococcus</i> (VRE). Limited work has been done to study the genomic epidemiology and population structure of linezolid-resistant <i>Enterococcus</i> (LRE) spp. in Victoria, Australia, and globally. We aimed to elucidate the genomic epidemiology and population structure of LRE in Victoria, Australia. We screened our local collection of <i>Enterococcus faecalis</i> and <i>Enterococcus faecium</i> for LRE from 2015 to 2023 and identified 15/349 (4.3 %) and 26/9,207 (0.28 %) <i>E. faecalis</i> and <i>E. faecium</i>, respectively, which had either or both phenotypic and genotypic resistance to linezolid. We next contextualized the Victorian LRE isolates with a global set of 684 <i>E. faecalis</i> and 324 <i>E. faecium</i> genomes from public databases. Integrated phylogenetic and epidemiologic data suggested that the LRE isolates in Victoria were likely introduced through multiple independent events from international travellers, with evidence of putative linear plasmids co-carrying <i>vanA</i> and linezolid resistance genes. We observed a predominance of the linezolid resistance-conferring <i>optrA</i> gene in <i>E. faecalis</i> irrespective of source origin in both the global and Victorian collections, whereas in <i>E. faecium</i>, <i>cfr</i> and <i>cfr</i>(B) occurred more frequently among clinical isolates, with no apparent geographical signatures. Our study provides a genomic snapshot of a large global collection of LRE isolates and establishes the epidemiological context for LRE circulating in Victoria, Australia.