Bile salts and glycine as cogerminants for Clostridium difficile spores

Spore formation by Clostridium difficile is a significant obstacle to overcoming hospital-acquired C difficile-associated disease. Spores are resistant to heat, radiation, chemicals, and antibiotics, making a contaminated environment difficult to clean. To cause disease, however, spores must germinate and grow out as vegetative cells. The germination of C difficile spores has not been examined in detail. In an effort to understand the germination of C difficile spores, we characterized the response of C difficile spores to bile. We found that cholate derivatives and the amino acid glycine act as cogerminants. Deoxycholate, a metabolite of cholate produced by the normal intestinal flora, also induced germination of C difficile spores but prevented the growth of vegetative C. difficile. A model of resistance to C difficile colonization mediated by the normal bacterial flora is proposed.