Evolutionary dynamics of Clostridium difficile over short and long time scales

Miao He, Mohammed Sebaihia, Trevor D. Lawley, Richard A. Stabler, Lisa F. Dawson, Melissa J. Martin, Kathryn E. Holt, Helena M.B. Seth-Smith, Michael A. Quail, Richard Rance, Karen Brooks, Carol Churcher, David Harris, Stephen D. Bentley, Christine Burrows, Louise Clark, Craig Corton, Vicky Murray, Graham Rose, Scott ThurstonAndries Van Tonder, Danielle Walker, Brendan W. Wren, Gordon Dougan, Julian Parkhill

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Clostridium difficile has rapidly emerged as the leading cause of antibiotic-associated diarrheal disease, with the transcontinental spread of various PCR ribotypes, including 001, 017, 027 and 078. However, the genetic basis for the emergence of C. difficile as a human pathogen is unclear. Whole genome sequencing was used to analyze genetic variation and virulence of a diverse collection of thirty C. difficile isolates, to determine both macro and microevolution of the species. Horizontal gene transfer and large-scale recombination of core genes has shaped the C. difficile genome over both short and long time scales. Phylogenetic analysis demonstrates C. difficile is a genetically diverse species, which has evolved within the last 1.1-85 million years. By contrast, the disease-causing isolates have arisen from multiple lineages, suggesting that virulence evolved independently in the highly epidemic lineages.

Original languageEnglish
Pages (from-to)7527-7532
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
Publication statusPublished - 20 Apr 2010


  • Homologous recombination
  • Horizontal gene transfer
  • Single nucleotide polymorphism

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