Comparative genomics reveals the genetic diversity and plasticity of Clostridium tertium.

Clostridium tertium, increasingly recognized as the emerging human pathogen frequently isolated from environmental and clinical specimens, remains genetically underexplored despite its clinical relevance. This study aims to explore the genetic characteristics of C. tertium by genomic analysis. This study presented a comprehensive genomic investigation of 45 C. tertium strains from the GenBank database. Genome sizes (3.27-4.55 Mbp) and coding gene counts varied markedly across strains. Phylogenetic analyses based on 16S rRNA gene and core genome uncovered distinct intra-species lineages, including evolutionarily divergent clusters likely shaped by niche specialization. Pan-genomic analysis confirmed an open genome, with accessory and strain-specific genes enriched in functions related to environmental adaptation and regulation. Functional annotation further identified diverse virulence factor genes (e.g. clpP, nagK) and antibiotic resistance genes (e.g. vatB, tetA(P)) co-occurring with mobile genetic elements (MGEs), suggesting that horizontal gene transfer (HGT) may be a key driver of genome plasticity in C. tertium. Notably, one-third of the strains carried CRISPR-Cas systems, indicating the defense potential against exogenous genetic elements. C. tertium exhibited extensive genetic diversity and genome plasticity, probably driven by MGE-mediated HGT, defense mechanisms of CRISPR-Cas systems, and functional adaptation related to virulence and resistance. These traits may underlie its ability to colonize diverse environments and acquire pathogenicity and resistance.