RT Journal Article SR Electronic T1 Genomes of a major nosocomial pathogen Enterococcus faecium are shaped by adaptive evolution of the chromosome and plasmidome JF bioRxiv FD Cold Spring Harbor Laboratory SP 530725 DO 10.1101/530725 A1 S Arredondo-Alonso A1 J Top A1 AC Schürch A1 A McNally A1 S Puranen A1 M Pesonen A1 J Pensar A1 P Marttinen A1 JC Braat A1 MRC Rogers A1 W van Schaik A1 S Kaski A1 J Corander A1 RJL Willems YR 2019 UL http://biorxiv.org/content/early/2019/01/26/530725.abstract AB Enterococcus faecium is a gut commensal of many mammals but is also recognized as a major nosocomial human pathogen, as it is listed on the WHO global priority list of multi-drug resistant organisms. Previous research has suggested that nosocomial strains have multiple zoonotic origins and are only distantly related to those involved in human commensal colonization. Here we present the first comprehensive population-wide joint genomic analysis of hospital, commensal and animal isolates using both short- and long-read sequencing techniques. This enabled us to investigate the population plasmidome, core genome variation and genome architecture in detail, using a combination of machine learning, population genomics and genome-wide co-evolution analysis. We observed a high level of genome plasticity with large-scale inversions and heterogeneous chromosome sizes, collectively painting a high-resolution picture of the adaptive landscape of E. faecium, and identified plasmids as the main indicator for host-specificity. Given the increasing availability of long-read sequencing technologies, our approach could be widely applied to other human and animal pathogen populations to unravel fine-scale mechanisms of their evolution.