Evolutionary dynamics of Clostridium difficile over short and long time scales

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 16; pp. 7527 - 7532
• Main Authors: He, Miao, Sebaihia, Mohammed, Lawley, Trevor D, Stabler, Richard A, Dawson, Lisa F, Martin, Melissa J, Holt, Kathryn E, Seth-Smith, Helena M.B, Quail, Michael A, Rance, Richard, Brooks, Karen, Churcher, Carol, Harris, David, Bentley, Stephen D, Burrows, Christine, Clark, Louise, Corton, Craig, Murray, Vicky, Rose, Graham, Thurston, Scott, van Tonder, Andries, Walker, Danielle, Wren, Brendan W, Dougan, Gordon, Parkhill, Julian
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 20.04.2010; National Acad Sciences
• Subjects: Bacteria; Biological Sciences; Clostridioides difficile - genetics; Clostridium difficile; Computational Biology; Diarrhea; Epidemics; Evolution; Evolution, Molecular; Gene Expression Regulation, Bacterial; Gene transfer; Gene Transfer Techniques; Genetic diversity; Genome, Bacterial; Genomes; Genomics; Homologous recombination; Molecular Sequence Data; Pathogens; Phylogenetics; Phylogeny; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Recombination; Recombination, Genetic; Ribotyping; Sequence Analysis, DNA; Sequencing; Species Specificity; Time Factors; Virulence
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0914322107

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.