An update on Clostridioides difficile population structure and genomics

SUMMARYSince its first isolation in 1935, several thousand Clostridioides difficile isolates have been collected and analyzed. These isolates belong to a diverse phylogeny consisting of five main clades and at least three cryptic clades. While clade 1 represents the largest and most diverse of the clades, clades 2 and 5 are the best studied, consisting of several strains attributed to the most severe clinical outcomes and increased rates of spread/recurrence. Strains belonging to clades 3 and 4 are typically minor constituents of C. difficile infection (CDI) outbreaks but possess several distinctive genetic features (e.g., unique pathogenicity loci) that provide unique targets for clinical treatments. Much of the divergence between these clades is attributable to variation within the accessory C. difficile genome. These factors, in turn, are often associated with mobile genetic elements (e.g., prophage, transposons, and plasmids). The transfer of these elements between strains is implicated in the acquisition and co-evolution of antibiotic resistance and virulence factors. The continued transfer of these elements between strains and their variation across the C. difficile phylogeny emphasizes the need to include strains spanning multiple ribotypes/clades in phylogenetic and phenotypic studies.