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Article
Nature Genetics 38, 779 - 786 (2006)
Published online: 25 June 2006; | doi:10.1038/ng1830

The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome

Mohammed Sebaihia1, Brendan W Wren2, Peter Mullany3, Neil F Fairweather4, Nigel Minton5, Richard Stabler2, Nicholas R Thomson1, Adam P Roberts3, Ana M Cerdeño-Tárraga1, Hongmei Wang3, Matthew TG Holden1, Anne Wright4, Carol Churcher1, Michael A Quail1, Stephen Baker1, Nathalie Bason1, Karen Brooks1, Tracey Chillingworth1, Ann Cronin1, Paul Davis1, Linda Dowd1, Audrey Fraser1, Theresa Feltwell1, Zahra Hance1, Simon Holroyd1, Kay Jagels1, Sharon Moule1, Karen Mungall1, Claire Price1, Ester Rabbinowitsch1, Sarah Sharp1, Mark Simmonds1, Kim Stevens1, Louise Unwin1, Sally Whithead1, Bruno Dupuy6, Gordon Dougan1, Bart Barrell1 & Julian Parkhill1

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

2  Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

3  Eastman Dental Institute for Oral Health Care Sciences, University College London, 256 Gary's Inn Road, London WC1X 8LD, UK.

4  Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ, UK.

5  Centre for Biomolecular Sciences, Institute of Infection, Immunity and Inflammation, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

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

Correspondence should be addressed to Julian Parkhill parkhill@sanger.ac.uk

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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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