title: Genome-based characterization of hospital-adaptedEnterococcus faecalislineages.
abstract: Vancomycin-resistantEnterococcus faecalis(VREfs) is an important nosocomial pathogen1,2. We undertook whole genome sequencing ofE. faecalisassociated with bloodstream infection in the UK and Ireland over more than a decade to determine the population structure and genetic associations with hospital adaptation. Three lineages predominated in the population, two of which (L1 and L2) were nationally distributed, and one (L3) geographically restricted. Genome comparison with a global collection identified that L1 and L3 were also present in the USA, but were genetically distinct. Over 90% of VREfs belonged to L1-L3, with resistance acquired and lost multiple times in L1 and L2, but only once followed by clonal expansion in L3. Putative virulence and antibiotic resistance genes were over-represented in L1, L2 and L3 isolates combined, versus the remainder. Each of the three main lineages contained a mixture of vancomycin-resistant and -susceptibleE. faecalis(VSEfs), which has important implications for infection control and antibiotic stewardship.
authors.affiliation: Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Kathy E
authors.initials: KE
authors.lastname: Raven
authors.affiliation: Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; Clinical Microbiology and Public Health Laboratory, Public Health England, Box 236, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Theodore
authors.initials: T
authors.lastname: Gouliouris
authors.affiliation: British Society for Antimicrobial Chemotherapy, Griffin House, 53 Regent Place, Birmingham B1 3NJ, UK; North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: Rosy
authors.initials: R
authors.lastname: Reynolds
authors.affiliation: Culture Collections, Public Health England, Porton Down, Salisbury SP4 0JG, UK.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Russell
authors.affiliation: Clinical Microbiology and Public Health Laboratory, Public Health England, Box 236, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; British Society for Antimicrobial Chemotherapy, Griffin House, 53 Regent Place, Birmingham B1 3NJ, UK.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Brown
authors.affiliation: Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; Clinical Microbiology and Public Health Laboratory, Public Health England, Box 236, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: M Estée
authors.initials: ME
authors.lastname: Török
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK; London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock