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Mechanisms of Clostridium difficile spore germination

艰难梭菌孢子萌发机制

基本信息

批准号：
10369015
负责人：
Joe Sorg
金额：
$ 44.05万
依托单位：
TEXAS A&M UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10369015
关键词：
Air Alleles Amino Acids Anaerobic Bacteria Antibiotic Resistance Antibiotics Appearance Bacillus subtilis Bacteria Bile Acids Binding Biological Assay Cell Wall Cells Chenodeoxycholic Acid Clostridium difficile Complex Data Disease Endospore-Forming Bacteria Environment Epidemic Excretory function Exposure to Gastrointestinal tract structure Genes Genetic Screening Germ Cells Germination Glycine Growth Healthcare Systems Hospitals Immunocompromised Host Incubated Infection Knowledge Lead LytA enzyme Mediating Membrane Molecular Molecular Target Morbidity - disease rate Mothers Mutagenesis Mutate Organism Pathogenesis Pathway interactions Patients Peptide Hydrolases Phase Phenotype Process Production Proteins Reaction Recombinants Reporting Reproduction spores Research Personnel Risk Role Signal Transduction Signaling Protein Site Surface Symptoms Taurocholic Acid Testing Toxin United States Work antibiotic-associated diarrhea base combat cost cost estimate design endolysin experimental study health care settings hybrid protein inhibitor mortality mouse model mutant novel novel therapeutics protein complex receptor validation studies

项目摘要

Clostridium difficile is the leading cause of antibiotic-associated diarrhea in the hospital and long term health care settings. In addition to the patient toll, the treatment-associated costs of C. difficile infections to the United States healthcare system have been estimated at $5 billion. Although the rate of C. difficile infection in the United States is rising, surprisingly little is known about the mechanisms of C. difficile pathogenesis. C. difficile is believed to be acquired by the host in the form of a dormant spore. To cause disease, the spore must respond in the gastrointestinal tract to signals that trigger germination, thereby allowing growth as a vegetative bacterium, toxin production and subsequent spore formation before excretion into the environment. Taurocholic acid, a bile acid normally found in the GI tract, and glycine are co- germinants for C. difficile spores. Another bile acid, chenodeoxycholic acid, inhibits taurocholic acid-mediated germination and is toxic for C. difficile vegetative growth. In prior work, the molecular target of bile acids on the C. difficile spore was identified - identifying the first C. difficile spore germinant receptor. This led to the finding that C. difficile spore germination proceeds through a novel, ‘outside – in’ germination pathway. More recently, the target of the amino acid co-germinants on the C. difficile spore was identified. In this proposal, the investigator proposes to: (1) characterize how the C. difficile ‘germinosome’ proteins interact; (2) define the mechanism of localization of these proteins in the C. difficile spore; (3) globally identify YabG protease targets; and (4) characterize the impact of these targets on C. difficile pathogenesis. Successful completion of the experiments outlined herein will extend the understanding of the mechanisms of C. difficile germination, open new avenues in the study of C. difficile spore formation and spore germination.

艰难梭菌是医院和长期抗生素相关性腹泻的主要原因