Journal
GENOME BIOLOGY AND EVOLUTION
Volume 6, Issue 12, Pages 3159-3170Publisher
OXFORD UNIV PRESS
DOI: 10.1093/gbe/evu248
Keywords
evolution; phylogeny; toxin locus
Categories
Funding
- Oxford Partnership Comprehensive Biomedical Research Centre
- UKCRC Modernising Medical Microbiology Consortium - UKCRC Translational Infection Research Initiative
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- National Institute for Health Research on behalf of the Department of Health [G0800778]
- Wellcome Trust [087646/Z/08/Z]
- NIHR
- NIHR for Health Protection Research Unit
- Department of Health's NIHR Biomedical Research Centres
- MRC [G0800778, MR/K010174/1] Funding Source: UKRI
- Medical Research Council [MR/K010174/1B, G0800778, MR/K010174/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10047, HPRU-2012-10080] Funding Source: researchfish
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The symptoms of Clostridium difficile infection are caused by two closely related toxins, TcdA and TcdB, which are encoded by the 19.6 kb Pathogenicity Locus (PaLoc). The PaLoc is variably present among strains, and in this respect it resembles a mobile genetic element. The C. difficile population structure consists mainly of five phylogenetic clades designated 1-5. Certain genotypes of clade 5 are associated with recently emergent highly pathogenic strains causing human disease and animal infections. The aim of this study was to explore the evolutionary history of the PaLoc in C. difficile clade 5. Phylogenetic analyses and annotation of clade 5 PaLoc variants and adjoining genomic regions were undertaken using a representative collection of toxigenic and nontoxigenic strains. Comparison of the core genome and PaLoc phylogenies obtained for clade 5 and representatives of the other clades identified two distinct PaLoc acquisition events, one involving a toxin A(+)B(+) PaLoc variant and the other an A(-)B(+) variant. Although the exact mechanism of each PaLoc acquisition is unclear, evidence of possible homologous recombination with other clades and between clade 5 lineages was found within the PaLoc and adjacent regions. The generation of nontoxigenic variants by PaLoc loss via homologous recombination with PaLoc-negative members of other clades was suggested by analysis of cdu2, although none is likely to have occurred recently. A variant of the putative holin gene present in the clade 5 A(-)B(+) PaLoc was likely acquired via allelic exchange with an unknown element. Fine-scale phylogenetic analysis of C. difficile clade 5 revealed the extent of its genetic diversity, consistent with ancient evolutionary origins and a complex evolutionary history for the PaLoc.
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