Evolutionary dynamics of Clostridium difficile over short and long time scales.

Miao He; Mohammed Sebaihia; Trevor D Lawley; Richard A Stabler ORCID logo; Lisa F Dawson ORCID logo; Melissa J Martin; Kathryn E Holt ORCID logo; Helena MB Seth-Smith; Michael A Quail; Richard Rance; +15 more... Karen Brooks; Carol Churcher; David Harris; Stephen D Bentley; Christine Burrows; Louise Clark; Craig Corton; Vicky Murray; Graham Rose; Scott Thurston; Andries van Tonder; Danielle Walker; Brendan W Wren ORCID logo; Gordon Dougan; Julian Parkhill; (2010) Evolutionary dynamics of Clostridium difficile over short and long time scales. Proceedings of the National Academy of Sciences of the United States of America, 107 (16). pp. 7527-7532. ISSN 0027-8424 DOI: 10.1073/pnas.0914322107
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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.

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