Bile salts and glycine as co-germinants for Clostridium difficile spores

Department of Molecular Biology and Microbiology, Tufts University, School of Medicine, Boston, MA

^* To whom correspondence should be addressed. Email: linc.sonenshein{at}tufts.edu.

	Abstract

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. 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 co-germinants. 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.