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Journal of Bacteriology, October 2006, p. 7297-7305, Vol. 188, No. 20
0021-9193/06/$08.00+0     doi:10.1128/JB.00664-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Comparative Phylogenomics of Clostridium difficile Reveals Clade Specificity and Microevolution of Hypervirulent Strains

R. A. Stabler,1 D. N. Gerding,2 J. G. Songer,3 D. Drudy,4 J. S. Brazier,5 H. T. Trinh,3 A. A. Witney,6 J. Hinds,6 and B. W. Wren1*

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom,1 Infectious Disease Section and Research Service, Department of Medicine, Hines Veterans Affairs Hospital and Loyola University Stritch School of Medicine, Hines, Illinois 60141,2 Department of Veterinary Science and Microbiology, University of Arizona, Tucson, Arizona 85721,3 Centre for Food Safety, University College Dublin, Belfield, Dublin 4, Ireland,4 Anaerobe Reference Laboratory, NPHS Microbiology Cardiff, University Hospital of Wales, Cardiff CF14 4XW, United Kingdom,5 Bacterial Microarray Group, Medical Microbiology, Department of Cellular and Molecular Medicine, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom6

Received 10 May 2006/ Accepted 30 July 2006

Clostridium difficile is the most frequent cause of nosocomial diarrhea worldwide, and recent reports suggested the emergence of a hypervirulent strain in North America and Europe. In this study, we applied comparative phylogenomics (whole-genome comparisons using DNA microarrays combined with Bayesian phylogenies) to model the phylogeny of C. difficile, including 75 diverse isolates comprising hypervirulent, toxin-variable, and animal strains. The analysis identified four distinct statistically supported clusters comprising a hypervirulent clade, a toxin A– B+ clade, and two clades with human and animal isolates. Genetic differences among clades revealed several genetic islands relating to virulence and niche adaptation, including antibiotic resistance, motility, adhesion, and enteric metabolism. Only 19.7% of genes were shared by all strains, confirming that this enteric species readily undergoes genetic exchange. This study has provided insight into the possible origins of C. difficile and its evolution that may have implications in disease control strategies.

* Corresponding author. Mailing address: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: 44 207 927 2288. Fax: 44 207 637 4314. E-mail: Brendan.Wren{at}lshtm.ac.uk.

Journal of Bacteriology, October 2006, p. 7297-7305, Vol. 188, No. 20
0021-9193/06/$08.00+0     doi:10.1128/JB.00664-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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