title: Evolutionary dynamics ofEnterococcus faeciumreveals complex genomic relationships between isolates with independent emergence of vancomycin resistance.
abstract: Enterococcus faecium, a major cause of hospital-acquired infections, remains problematic because of its propensity to acquire resistance to vancomycin, which currently is considered first-line therapy. Here, we assess the evolution and resistance acquisition dynamics ofE. faeciumin a clinical context using a series of 132 bloodstream infection isolates from a single hospital. All isolates, of which 49 (37 %) were vancomycin-resistant, underwent whole-genome sequencing.E. faeciumwas found to be subject to high rates of recombination with little evidence of sequence importation from outside the localE. faeciumpopulation. Apart from disrupting phylogenetic reconstruction, recombination was frequent enough to invalidate MLST typing in the identification of clonal expansion and transmission events, suggesting that, where available, whole-genome sequencing should be used in tracing the epidemiology ofE. faeciumnosocomial infections and establishing routes of transmission. Several forms of the Tn1549-like element-vanBgene cluster, which was exclusively responsible for vancomycin resistance, appeared and spread within the hospital during the study period. Several transposon gains and losses and instances ofin situevolution were inferred and, although usually chromosomal, the resistance element was also observed on a plasmid background. There was qualitative evidence for clonal expansions of both vancomycin-resistant and vancomycin-susceptibleE. faeciumwith evidence of hospital-specific subclonal expansion. Our data are consistent with continuing evolution of this established hospital pathogen and confirm hospital vancomycin-susceptible and vancomycin-resistantE. faeciumpatient transmission events, underlining the need for careful consideration before modifying currentE. faeciuminfection control strategies.
authors.affiliation: 2​ Antibiotic Resistance & Mobile Elements Group, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.|1​ Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: van Hal
authors.affiliation: 3​ Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Camilla L C
authors.initials: CLC
authors.lastname: Ip
authors.affiliation: 4​ Oxford Martin School, University of Oxford, 34 Broad Street, Oxford, UK.
authors.forename: M Azim
authors.initials: MA
authors.lastname: Ansari
authors.affiliation: 5​ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: 2​ Antibiotic Resistance & Mobile Elements Group, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.|6​ Molecular Medicine Research Group, School of Medicine, University of Western Sydney, Sydney, NSW, Australia.
authors.forename: Bjorn A
authors.initials: BA
authors.lastname: Espedido
authors.affiliation: 2​ Antibiotic Resistance & Mobile Elements Group, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia.|6​ Molecular Medicine Research Group, School of Medicine, University of Western Sydney, Sydney, NSW, Australia.
authors.forename: Slade O
authors.initials: SO
authors.lastname: Jensen
authors.affiliation: 3​ Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Rory
authors.initials: R
authors.lastname: Bowden
mesh_terms: D015373:Bacterial Typing Techniques; D016984:Enterococcus faecium / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000235:genetics*; D058885:Multilocus Sequence Typing; D010802:Phylogeny; D013045:Species Specificity; D020713:Vancomycin Resistance / Q000235:genetics*
keywords: Enterococcus faecium; infection control; multi-locus sequence typing; recombination; transposon; vancomycin resistance