title: Comparative phylogenomics of Clostridium difficile reveals clade specificity and microevolution of hypervirulent strains.
abstract: 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.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: R A
authors.initials: RA
authors.lastname: Stabler
authors.forename: D N
authors.initials: DN
authors.lastname: Gerding
authors.forename: J G
authors.initials: JG
authors.lastname: Songer
authors.forename: D
authors.initials: D
authors.lastname: Drudy
authors.forename: J S
authors.initials: JS
authors.lastname: Brazier
authors.forename: H T
authors.initials: HT
authors.lastname: Trinh
authors.forename: A A
authors.initials: AA
authors.lastname: Witney
authors.forename: J
authors.initials: J
authors.lastname: Hinds
authors.forename: B W
authors.initials: BW
authors.lastname: Wren
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D016360:Clostridioides difficile / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial / Q000235:genetics; D044404:Genomic Islands; D006801:Humans; D009068:Movement; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D014774:Virulence
chemical_list: D001427:Bacterial Toxins; D004269:DNA, Bacterial