Clostridium difficile spore biology: sporulation, germination, and spore structural proteins

• The Clostridium difficile sporulation process is substantially different from the Bacillus subtilis paradigm.
• Novel and unidentified proteins are involved in the formation of the C. difficile spore coat layer.
• C. difficile possesses an exosporium layer that may play a role in pathogenesis.
• The catalytically dead serine protease, CspC, acts as a bile salt germination receptor (GR).

Clostridium difficile is a Gram-positive, spore-forming obligate anaerobe and a major nosocomial pathogen of worldwide concern. Owing to its strict anaerobic requirements, the infectious and transmissible morphotype is the dormant spore. In susceptible patients, C. difficile spores germinate in the colon to form the vegetative cells that initiate Clostridium difficile infections (CDI). During CDI, C. difficile induces a sporulation pathway that produces more spores; these spores are responsible for the persistence of C. difficile in patients and horizontal transmission between hospitalized patients. Although important to the C. difficile lifecycle, the C. difficile spore proteome is poorly conserved when compared to members of the Bacillus genus. Further, recent studies have revealed significant differences between C. difficile and Bacillus subtilis at the level of sporulation, germination, and spore coat and exosporium morphogenesis. In this review, the regulation of the sporulation and germination pathways and the morphogenesis of the spore coat and exosporium will be discussed.