TheClostridioides difficilespecies problem: global phylogenomic analysis uncovers three ancient, toxigenic, genomospecies
Knight DR., Imwattana K., Kullin B., Guerrero-Araya E., Paredes-Sabja D., Didelot X., Dingle KE., Eyre DW., Rodríguez C., Riley TV.
AbstractClostridioides difficileinfection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen acrossC. difficileunderscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000C. difficilegenomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI-III. The emergence of these three novel genomospecies predates clades C1-5 by millions of years, rewriting the global population structure ofC. difficilespecifically and taxonomy of thePeptostreptococcaceaein general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution ofC. difficileand close relatives. Beyond the taxonomic ramifications, this work impacts the diagnosis of CDI worldwide.