title: Pyrosequencing-based comparative genome analysis of the nosocomial pathogen Enterococcus faecium and identification of a large transferable pathogenicity island.
abstract: BACKGROUND
  The Gram-positive bacterium Enterococcus faecium is an important cause of nosocomial infections in immunocompromized patients.
  
  
  RESULTS
  We present a pyrosequencing-based comparative genome analysis of seven E. faecium strains that were isolated from various sources. In the genomes of clinical isolates several antibiotic resistance genes were identified, including the vanA transposon that confers resistance to vancomycin in two strains. A functional comparison between E. faecium and the related opportunistic pathogen E. faecalis based on differences in the presence of protein families, revealed divergence in plant carbohydrate metabolic pathways and oxidative stress defense mechanisms. The E. faecium pan-genome was estimated to be essentially unlimited in size, indicating that E. faecium can efficiently acquire and incorporate exogenous DNA in its gene pool. One of the most prominent sources of genomic diversity consists of bacteriophages that have integrated in the genome. The CRISPR-Cas system, which contributes to immunity against bacteriophage infection in prokaryotes, is not present in the sequenced strains. Three sequenced isolates carry the esp gene, which is involved in urinary tract infections and biofilm formation. The esp gene is located on a large pathogenicity island (PAI), which is between 64 and 104 kb in size. Conjugation experiments showed that the entire esp PAI can be transferred horizontally and inserts in a site-specific manner.
  
  
  CONCLUSIONS
  Genes involved in environmental persistence, colonization and virulence can easily be aquired by E. faecium. This will make the development of successful treatment strategies targeted against this organism a challenge for years to come.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. w.vanschaik@umcutrecht.nl
authors.forename: Willem
authors.initials: W
authors.lastname: van Schaik
authors.forename: Janetta
authors.initials: J
authors.lastname: Top
authors.forename: David R
authors.initials: DR
authors.lastname: Riley
authors.forename: Jos
authors.initials: J
authors.lastname: Boekhorst
authors.forename: Joyce E P
authors.initials: JE
authors.lastname: Vrijenhoek
authors.forename: Claudia M E
authors.initials: CM
authors.lastname: Schapendonk
authors.forename: Antoni P A
authors.initials: AP
authors.lastname: Hendrickx
authors.forename: Isaäc J
authors.initials: IJ
authors.lastname: Nijman
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Rob J L
authors.initials: RJ
authors.lastname: Willems
mesh_terms: D001435:Bacteriophages / Q000235:genetics / Q000648:ultrastructure; D001483:Base Sequence; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000235:genetics* / Q000472:pathogenicity / Q000821:virology; D016680:Genome, Bacterial; D044404:Genomic Islands; D046529:Microscopy, Electron, Transmission; D010802:Phylogeny; D014774:Virulence
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