Genomic investigation of the emergence of vancomycin-resistant .

Vancomycin-resistant (VRE) is an increasingly identified cause of human disease, with most infections resulting from the and genotypes; less is known about other clinically relevant genotypes. Here we report a genomic exploration of a VRE (VREfm), which arose during a single infectious episode. The genomes of the vancomycin-susceptible (VSEfm) recipient and resulting VREfm were subjected to long-read sequencing and closed, with whole-genome alignments, cross-mapping and orthologue clustering used to identify genomic variation. Three key differences were identified. (i) The VREfm chromosome gained a 142.6 kb integrative conjugative element (ICE) harbouring the locus. (ii) The native ligase () was disrupted by an IS insertion. (iii) A large 1.74 Mb chromosomal inversion of unknown consequence occurred. Alignment and phylogenetic-based comparisons of the VREfm with a global collection of -harbouring genomes identified strong similarities in the 120-160 kb genomic region surrounding suggestive of a common mobile element and integration site, irrespective of the diverse taxonomic, geographical and host origins of the isolates. This isolate diversity revealed that this putative ICE (and its source) is globally disseminated and is capable of being acquired by different genera. Although the incidence of VREfm is low, understanding its emergence and potential for spread is crucial for the ongoing efforts to reduce antimicrobial resistance.