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Abstract

We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.

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Acknowledgements

We would like to acknowledge the support of the Wellcome Trust Sanger Institute core sequencing and informatics groups. We thank D. Gerding and G. Songer for provision of C. difficile strains, F. Barbut and J. Emerson for help with the antibiotic susceptibility tests, and the BUGs microarray facility at St. George's Hospital for provision of the C. difficile 630 microarray. This work was supported by the Wellcome Trust.

Author information

Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.

    • Mohammed Sebaihia
    • , Nicholas R Thomson
    • , Ana M Cerdeño-Tárraga
    • , Matthew TG Holden
    • , Carol Churcher
    • , Michael A Quail
    • , Stephen Baker
    • , Nathalie Bason
    • , Karen Brooks
    • , Tracey Chillingworth
    • , Ann Cronin
    • , Paul Davis
    • , Linda Dowd
    • , Audrey Fraser
    • , Theresa Feltwell
    • , Zahra Hance
    • , Simon Holroyd
    • , Kay Jagels
    • , Sharon Moule
    • , Karen Mungall
    • , Claire Price
    • , Ester Rabbinowitsch
    • , Sarah Sharp
    • , Mark Simmonds
    • , Kim Stevens
    • , Louise Unwin
    • , Sally Whithead
    • , Gordon Dougan
    • , Bart Barrell
    •  & Julian Parkhill
  2. Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

    • Brendan W Wren
    •  & Richard Stabler
  3. Eastman Dental Institute for Oral Health Care Sciences, University College London, 256 Gary's Inn Road, London WC1X 8LD, UK.

    • Peter Mullany
    • , Adam P Roberts
    •  & Hongmei Wang
  4. Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ, UK.

    • Neil F Fairweather
    •  & Anne Wright
  5. Centre for Biomolecular Sciences, Institute of Infection, Immunity and Inflammation, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

    • Nigel Minton
  6. Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 Rue du Dr Roux, 75724 Paris cedex 15, France.

    • Bruno Dupuy

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Julian Parkhill.

Supplementary information

PDF files

  1. 1.

    Supplementary Table 1

    Features of the C. difficile CRISPRs.

  2. 2.

    Supplementary Table 2

    Antibiotic susceptibility of C. difficile strain 630.

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DOI

https://doi.org/10.1038/ng1830

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