Molecular Pathogenesis of Enterotoxigenic Escherichia coli Infections

产肠毒素大肠杆菌感染的分子发病机制

• 批准号: 8965936
• 负责人: James Michael Fleckenstein
• 金额: --
• 依托单位: ST. LOUIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8965936
• 关键词: Address; Adherence; Adhesions; Antigens; Area; Bacteria; Bacterial Adhesins; Cell Communication; Cell Cycle Kinetics; Cell Line; Cell Surface Receptors; Cells; Cholera; Complex; Cytolysis; DNA Microarray Chip; Data; Developed Countries; Development; Diarrhea; Disease; Disease Outbreaks; Enteral; Epithelial; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Event; Failure; Flagella; Genes; Genetic Transcription; Goals; Health; Heating; Heterogeneity; Human; Immune response; Infection; Intestines; Investigation; Kinetics; Label; Laboratories; Membrane; Methodology; Molecular; Morbidity - disease rate; Nature; New Agents; Organism; Pathogenesis; Plasmids; Prevention; Prevention approach; Proteins; Pseudomonas; Research; Role; Soldier; Structure; Surface; Toxin; Translating; United States; Urinary tract infection; Vaccines; Veterans; Virulence; Virulence Factors; design; enteric pathogen; enterotoxigenic Escherichia coli; fimbria; foodborne outbreak; global health; immunogenic; insight; microscopic imaging; mortality; novel; novel strategies; pathogen; pathogenic Escherichia coli; public health relevance; release factor; research and development; response; time use; tool; vaccine development

DESCRIPTION (provided by applicant): The enterotoxigenic Escherichia coli (ETEC) are a genetically diverse type of pathogenic E. coli that cause astounding numbers of cases of diarrheal illness worldwide, and have emerged as a cause of large-scale outbreaks of diarrhea in the United States. These organisms share the ability to produce, secrete, and deliver heat-stable (ST) and/or heat-liable (LT) toxins to the intestinal lining cells ultimately causing diarrhea, which can be severe and cholera-like. The toxin genes encoded on plasmids, were identified shortly after the discovery of these toxin-producing E. coli more than 40 years ago. Most research on ETEC until very recently focused on a small number of molecules, namely the toxins themselves and plasmid-encoded fingerlike colonization factors (CFs). Unfortunately, vaccine development centered on these antigens alone has proven to be very challenging in part because of the heterogeneity of the CF molecules and the fact that the toxins do not appear to afford complete protection against disease (in the case of LT), or are not immunogenic (as is the case for ST). The recent failure of several vaccines incorporating these antigens has prompted both a search for alternative strategiesand a return to basic pathogenesis studies in order to address gaps in our understanding of how these globally important pathogens cause disease. While much is known about the molecular action of these toxins once they enter host cells, very little is known about how the bacteria effectively deliver these toxins to their respective cell surface receptors. These studies will use recently developed molecular tools, capitalize on recent discoveries of new agents, and exploit the state-of-the-art methodology to define the roll of novel molecules on the surface of ETEC that promote the effective delivery of these toxins. The long-term goal of these studies is to translate this information into rational design of a safe, effective, and broadly protective ETEC vaccine.

描述（由申请人提供）：