Exploring the genomes of the Norwegian vancomycin resistant enterococci

Abstract

Enterococci are gram-positive commensals in the human gut microbiota that may cause severe infections, especially in immunocompromised and hospitalised patients. Their ability to accumulate antimicrobial resistance and virulence genes has been vital in their evolution into leading pathogens. Vancomycin resistant enterococci (VRE) are among the most important resistant pathogens causing outbreaks worldwide. In this study, we aimed to examine recent developments in the epidemiology of VRE in Norway related to the occurrence of novel van-types and the increasing incidence of VRE since 2010. By analysing whole genome sequencing data produced in this project, we identified and described the first Norwegian vanD-type VRE isolates from two patients and reported a novel vanD-subtype and genomic islands harbouring the vanD gene clusters and reported vanD gene cluster in vancomycin resistant Enterococcus casseliflavus for the first time. Different vanD subtypes harbouring genomic islands and phylogenetic, genomic distance confirmed that the isolates of the two cases are clonally unrelated. Additionally, we identified the first vanE-type VRE isolates in Norway recovered from the same patient and described the mobile genetic element harbouring (MGE) the vanE gene cluster, its insertion site, and explained why one isolate expressed inducible low level and the other isolate constitutive low level vancomycin resistance. Moreover, we conducted the first comprehensive study on Norwegian VRE and vancomycin susceptible Enterococcus faecium (VSEfm) at the genomic level and identified the most prevalent cluster types (CTs), compared their virulomes, and MGEs harbouring the van gene clusters. In conclusion the population structure of E. faecium in Norway is shaped by globally prevalent clones, particularly concurrent European CTs, with similar dynamic ST sweeps. The dominant CTs of VREfm have acquired more virulence determinants than the more diverse local VSEfm population.