C. difficile spore germination receptors

University Of Nevada Las Vegas, Las Vegas NV

Investigators

Abstract

This research award in the Chemistry of Life Processes (CLP) program supports work by Professor Abel-Santos at the University of Nevada Las Vegas to study the mechanism of Clostridium difficile spore germination using kinetic methods and molecular probes. Kinetic analysis of C. difficile spore germination is used to determine how small molecules (germinants) interact with C. difficile spores to induce germination. Using germinant analogs as activators and/or inhibitors of C. difficile spore germination allows defining which parts of the germinant molecules are required for interaction with the C. difficile germination machinery. Finally, photoreactive analogs serve to characterize which spore protein(s) bind to the germinants. These complementary experiments will allow mapping interactions between germinants and C. difficile spores. By using techniques from chemistry, biochemistry, and microbiology, we are able to study a hitherto intractable biological problem. The project has a broader impact on education, as a diverse group of students receives multidisciplinary training in chemistry, biochemistry, and microbiology to provide them with in-depth exposure to both physical and biological sciences. Since spore germination is the fist step in establishing infection by C. difficile, a molecular-level understanding of how spores germinate could eventually lead to new approaches to prevent C. difficile associated disease. In a more general sense, sporulating bacteria are used beneficially to control agricultural insect pests. Furthermore, some sporulating bacteria species can be used to produce precursors used by the chemical and pharmaceutical industry. Thus, the chemical techniques and knowledge developed in this project will be applicable to understanding the germination process in important bacteria species.