title: Modulation of virulence within a pathogenicity island in vancomycin-resistant Enterococcus faecalis.
abstract: Enterococci are members of the healthy human intestinal flora, but are also leading causes of highly antibiotic-resistant, hospital-acquired infection. We examined the genomes of a strain of Enterococcus faecalis that caused an infectious outbreak in a hospital ward in the mid-1980s (ref. 2), and a strain that was identified as the first vancomycin-resistant isolate in the United States, and found that virulence determinants were clustered on a large pathogenicity island, a genetic element previously unknown in this genus. The pathogenicity island, which varies only subtly between strains, is approximately 150 kilobases in size, has a lower G + C content than the rest of the genome, and is flanked by terminal repeats. Here we show that subtle variations within the structure of the pathogenicity island enable strains harbouring the element to modulate virulence, and that these variations occur at high frequency. Moreover, the enterococcal pathogenicity island, in addition to coding for most known auxiliary traits that enhance virulence of the organism, includes a number of additional, previously unstudied genes that are rare in non-infection-derived isolates, identifying a class of new targets associated with disease which are not essential for the commensal behaviour of the organism.
authors.affiliation: nathan-shankar@ouhsc.eduDepartment of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, Oklahoma 73190, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Shankar
authors.forename: Arto S
authors.initials: AS
authors.lastname: Baghdayan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D003428:Cross Infection / Q000382:microbiology; D013293:Enterococcus faecalis / Q000235:genetics* / Q000472:pathogenicity*; D005798:Genes, Bacterial / Q000235:genetics; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics; D014481:United States; D020713:Vancomycin Resistance / Q000235:genetics*; D014774:Virulence / Q000235:genetics