Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia; School of Biomedical Sciences, the University of Western Australia, Nedlands, Australia
School of Biomedical Sciences, the University of Western Australia, Nedlands, Australia; Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Department of Pathology, University of Cape Town, Cape Town, South Africa
Enzo Guerrero-Araya
Microbiota-Host Interactions and Clostridia Research Group, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile; Millenium Nucleus in the Biology of Intestinal Microbiota, Santiago, Chile
Daniel Paredes-Sabja
Microbiota-Host Interactions and Clostridia Research Group, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile; Millenium Nucleus in the Biology of Intestinal Microbiota, Santiago, Chile; Department of Biology, Texas A&M University, College Station, United States
School of Life Sciences and Department of Statistics, University of Warwick, Coventry, United Kingdom
Kate E Dingle
Nuffield Department of Clinical Medicine, University of Oxford, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom
Big Data Institute, Nuffield Department of Population Health, University of Oxford, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom
Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia; School of Biomedical Sciences, the University of Western Australia, Nedlands, Australia; Department of Microbiology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores 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 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, and 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 of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work may impact the diagnosis of CDI.
