Overall, the data presented in this thesis contribute to the knowledge of C. difficile spores to overcome the effects of inhibitory bile salts facilitating germination in ileal contents from non-antibiotic treated mice.

Bile salts, calcium, and amino acids synergize together to decrease the required concentrations to physiological levels. difficile spores is regulated within the gastrointestinal tract by pH and availability of specific germinants, limiting germination to the ileum. Data presented in this thesis indicate that germination of C. In this work, I describe for the first time an additional germination pathway activated by bile salts and intestinal calcium. The goals of this thesis are to describe the earliest events of germination including the specific conditions that facilitate germination, the mechanism of bile salts amino acid induced germination, and characterize the role of calcium. The amino acid receptor has yet to be discovered. difficile germinates in response to the combination of amino acids and bile salts with a unique pseudo-protease receptor, CspC. difficile spores germinate through a unique mechanism. difficile genome does not encode any orthologs of these receptors, C. Much is known about bacterial spore germination in Bacillus spp., however, since the C. These germinants are typically amino acids that interact with specific receptors found within the spore (GerA). Germination occurs after specific environmental cues, known as germinants, signal to the spore that conditions are favorable for vegetative cell growth. Germination is the first pathogenic event that occurs after ingestion of the spore and thus, is required for disease. difficile spores are the infectious particles when a susceptible patient ingests a spore, it becomes reactivated in the small intestine through a process known as germination. These spores allow the bacterium to survive in harsh environmental conditions such as oxygen, low pH, ethanol, dessication, etc. Spo0A phosphorylation leads to activation of a cascade of compartment specific transcription factors and the production of mature dormant spores. Sporulation occurs when bacterial growth conditions are unfavorable which leads to the phosphorylation of the major transcription factor Spo0A. difficile spores are produced through a highly regulated process known as sporulation. difficile infection is a toxin-mediated disease, however, they are dependent on the ability to produce spores. These symptoms are caused by the production of two large exotoxins (TcdA and TcdB), that attack the host intestinal epithelium. difficile infections cause symptoms ranging from severe diarrhea, to pseudomembranous colitis, toxin megacolon, and even death.

AbstractClostridium difficile is an anaerobic spore forming bacterium that is an important human pathogen and a leading cause of hospital acquired infectious diarrhea worldwide.

C.difficile spore