Role of circadian rhythms in the susceptibility to Clostridium difficile infection

昼夜节律在艰难梭菌感染易感性中的作用

• 批准号: 9895923
• 负责人: Jerome Menet
• 金额: $ 21.59万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895923
• 关键词: Accounting; Adaptor Signaling Protein; Address; Affect; Anaerobic Bacteria; Animal Model; Antibiotics; Appearance; Bile Acid Biosynthesis Pathway; Bile Acids; Biological Process; Biology; Cells; Circadian Rhythms; Clinical; Clostridium difficile; Community-Acquired Infections; Cytoplasm; Data; Development; Digestion; Disease; Environment; Epidemic; Epithelial Cells; Exhibits; Exposure to; FZD1 gene; Family; Feedback; Flow Cytometry; Gene Expression; Genes; Genetic Transcription; Genome; Germination; Goals; Guanosine Triphosphate Phosphohydrolases; Hospitals; Impairment; Infection; Inflammation; Inflammatory Response; Leukocytes; Light; Mammalian Cell; Mammals; Mediating; Metabolic; Molecular; Monitor; Morbidity - disease rate; Mus; Nature; Nosocomial Infections; Organism; Pathogenicity; Pathologic; Patients; Periodicity; Phase; Physiology; Predisposition; Process; Proteins; Radiation; Recovery; Regulation; Reproduction spores; Resting Phase; Role; Severities; Site; Structure; Symptoms; Testing; Time; Toll-like receptors; Toxic effect; Toxin; United States; Virulence; Wild Type Mouse; bacterial resistance; base; circadian; circadian pacemaker; circadian regulation; design; differential expression; experimental study; feeding; host colonization; insight; intestinal epithelium; monocyte; mortality; mouse model; poliovirus receptor; receptor; receptor expression; recruit; response; rho; rho GTP-Binding Proteins; transcriptome sequencing; virtual

Project Summary Clostridium difficile is now the most common cause of hospital-acquired infections in the United States. This Gram-positive, spore-forming, strict anaerobe most commonly infects antibiotic- treated hosts, though community-acquired infections are on the rise for unknown reasons. To survive outside a host, C. difficile produces dormant spores. Spores are metabolically dormant forms of bacteria that are resistant to many harsh conditions (e.g., many cleaning agents, heat, radiation and antibiotics). In a host, C. difficile spores germinate in response to bile acids. Following C. difficile spore germination, the vegetative cells produce the toxins that trigger the host’s inflammatory response and that cause the primary symptoms of disease. Remarkably, the effectors of C. difficile infection (e.g., toxin receptor abundance and inflammation) exhibit strong circadian rhythms. These rhythms are generated by molecular circadian clocks found in virtually every mammalian cell, and which rely on transcriptional feedback loops to coordinate the rhythmic expression of about 10-15% of the genome. The circadian nature of the host physiology suggests that the normal host circadian rhythms may impact the efficiency with which C. difficile infects, colonizes and causes disease. In this exploratory application, the effects of host circadian biology on the ability of C. difficile to colonize and on the host’s inflammatory response to C. difficile infection will be explored.

项目总结