Virulence on the move: toxin plasmids drive diversity and disease in Clostridium perfringens

Clostridium perfringens is a Gram-positive anaerobe responsible for a wide spectrum of diseases in humans and animals, driven by an expanding arsenal of toxins. Notably, many of these virulence factors are encoded on mobile genetic elements, particularly conjugative plasmids, positioning mobile DNA at the centre of C. perfringens pathogenicity. Over the past decade, the pace of discovery has accelerated, with at least 11 new putative toxin-encoding genes identified, revealing an increasingly complex and dynamic toxin landscape. Here, we review advances in our understanding of toxin diversity and plasmid biology in C. perfringens, highlighting the remarkable plasticity of its mobile genome. We discuss how plasmid-encoded virulence, horizontal gene transfer and the emergence of novel plasmid families are reshaping current models of pathogenesis and evolution. We also consider key gaps in knowledge, including plasmid function, mobility and ecological context, and outline priorities for future genomic and functional studies. Together, these advances position C. perfringens as a compelling model to understand how mobile genetic elements drive virulence, adaptation and disease in bacterial pathogens.