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.
All data generated or analysed during this study are included in the manuscript and Supplementary Data which is hosted at Figshare http://doi.org/10.6084/m9.figshare.12471461.Data files on figshare include: Full MLST data for all 12000+ C. difficile genomes (Fig 1). Whole-genome ANI analyses (Table 1, Fig 3, Fig 5). Tree files for phylogenetic analyses (Fig 2, Fig 4). Pangenome data (Fig 6). Pan-GWAS data (Table 2). Comparative genomic analysis of virulence gene architecture (Fig 7).Note: Regarding the question below - Did your work use any previously published datasets (e.g., DNA sequence data, clinical trial data, field data)?We retrieved the entire collection of C. difficile genomes (taxid ID 1496) held at the NCBI Sequence Read Archive [https://www.ncbi.nlm.nih.gov/sra/]. The raw dataset (as of 1st January 2020) comprised 12,621 genomes. These genomes comprise hundreds, maybe thousands of publications. The individual accession numbers for all genomes analysed in this study are provided in the Supplementary Data at http://doi.org/10.6084/m9.figshare.12471461.
- Daniel R Knight
- Daniel R Knight
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Vaughn S Cooper, University of Pittsburgh, United States
- Received: October 25, 2020
- Accepted: June 8, 2021
- Accepted Manuscript published: June 11, 2021 (version 1)
© 2021, Knight et al.
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