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Modulation of virulence within a pathogenicity island in vancomycin-resistant Enterococcus faecalis

Naturevolume 417pages746750 (2002) | Download Citation

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Abstract

Enterococci are members of the healthy human intestinal flora, but are also leading causes of highly antibiotic-resistant, hospital-acquired infection1. 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 States3, 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.

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Acknowledgements

This work was supported by grants from the National Institutes of Health, American Heart Association and Research to Prevent Blindness. We thank M. Carson for help with generating the linear map of the pathogenicity island.

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Affiliations

  1. Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, Oklahoma, 73190, USA

    • Nathan Shankar
    •  & Arto S. Baghdayan
  2. Departments of Ophthalmology and Microbiology & Immunology, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, Oklahoma, 73190, USA

    • Michael S. Gilmore
  3. Immunology, University of Oklahoma Health Sciences Center, PO Box 26901

    • Michael S. Gilmore

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The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Nathan Shankar.

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https://doi.org/10.1038/nature00802

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