Genetic mechanisms governing sporulation initiation in Clostridioides difficile

As an anaerobe, Clostridioides difficile relies on the formation of a dormant spore for survival outside of the mammalian host's gastrointestinal tract. The spore is recalcitrant to desiccation, numerous disinfectants, UV light, and antibiotics, permitting long-term survival against environmental insults and efficient transmission from host to host. Although the morphological stages of spore formation are similar between C. difficile and other well-studied endospore-forming bacteria, the C. difficile genome does not appear to encode many of the known, conserved regulatory factors that are necessary to initiate sporulation in other spore-forming bacteria. The absence of early sporulation-specific orthologs suggests that C. difficile has evolved to control sporulation initiation in response to its unique and specific ecological niche and environmental cues within the host. Here, we review our current understanding and highlight the recent discoveries that have begun to unravel the regulatory pathways and molecular mechanisms by which C. difficile induces spore formation.