Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy

Abstract

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.

Clostridioides difficile strain-dependent and strain-independent adaptations to a microaerobic environment

“… C. difficile strains are genetically diverse due to a high rate of genome rearrangement [20, 25] and commonly have variable phenotypes clinically and in culture [26–30]. To determine whether increased tissue oxygenation is a common feature amongst strains during CDI, mice were infected with a C.…”

A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile

“…The three cryptic clades are extremely divergent (Figs 1 and 2a) and likely represent independent species or subspecies based on the genomic data [14]. Three of the five major clades contain epidemic sequence types (STs); C2 contains ST 1 (corresponding to RT 027), C4 contains ST 37 (RT 017) and C5 contains ST 11 (several RTs, including RT 078) [14]. To date, studies have been conducted on the role of AMR in the emergence and spread of two epidemic STs, 1 and 11 [10, 12, 13].…”

Genomic characterization of nine Clostridioides difficile strains isolated from Korean patients with Clostridioides difficile infection

“…However, further studies using molecular methods indicated a diversity of organisms in the genus Clostridium , and 16S rRNA phylogenetic analysis confirmed that C. difficile had less than 97% similarity with other species from the genus Clostridium . Currently, the genus Clostridioides includes two species, C. difficile and C. mangenotii [ 11 , 48 ].

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