Evolutionary dynamics of <i>Clostridium difficile</i> over short and long time scales

TLDR

Clostridium difficile has rapidly become the leading cause of antibiotic‑associated diarrhoea, spreading transcontinentally across ribotypes 001, 017, 027 and 078, yet the genetic basis for its emergence remains unclear. The study aimed to use whole‑genome sequencing of thirty diverse isolates to map both macro‑ and micro‑evolutionary patterns of C. difficile. Whole‑genome sequencing was performed on thirty isolates, followed by comparative genomic and phylogenetic analyses to assess genetic variation and virulence determinants.

Abstract

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.