Molecular Microbiology of Enterotoxigenic E. coli Pathogen-Host Interactions

产肠毒素大肠杆菌病原体-宿主相互作用的分子微生物学

• 批准号: 9926220
• 负责人: James Michael Fleckenstein
• 金额: $ 24.01万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-14 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926220
• 关键词: Acute; Address; Adhesions; Adjuvant; Amino Acids; Antigens; Architecture; Bacterial Adhesins; Bacterial Adhesion; Bangladeshi; Binding; Cell surface; Cells; Cessation of life; Chemistry; Child; Cholera; Chronic; Clustered Regularly Interspaced Short Palindromic Repeats; Complement; Developed Countries; Developing Countries; Development; Diarrhea; Disease; Disease susceptibility; Elements; Engineering; Epithelial; Epithelial Cells; Epithelium; Escherichia coli Infections; Event; Gene Expression; Genes; Genome; Glycocalyx; Glycoproteins; Glycoside Hydrolases; Goals; Goblet Cells; Growth; Human Volunteers; Immune response; In Vitro; Individual; Infection; Institutes; Intestinal Mucosa; Intestines; Investigation; Kinetics; Laboratories; Lead; Lectin; Malnutrition; Membrane; Membrane Proteins; Microbiology; Microscopy; Modeling; Molecular; Mucin-2 Staining Method; Mucins; Nature; Organism; Pathogenesis; Patients; Polysaccharides; Proteins; Proteomics; Risk Factors; Sanitation; Small Intestines; Structure; Surface; System; Testing; Thermogenesis; Time; Toxin; Vaccine Antigen; Vaccine Design; Vaccines; Virulence Factors; Water; Work; blood group; carcinoembryonic antigen-related cell adhesion molecules; confocal imaging; design; diarrheal disease; enterotoxigenic Escherichia coli; gastrointestinal epithelium; global health; glycosyltransferase; gut colonization; high risk; improved; intestinal epithelium; mutant; novel; novel strategies; pathogen; prevent; receptor; response; stem cells; therapy development; uptake; vaccine candidate; vaccine development

Project Summary/Abstract This work focuses on enterotoxigenic Escherichia coli (ETEC), globally the most common bacterial cause of serious diarrheal illness. These illnesses threaten the lives of many children in poor regions of the world where sanitation and clean water are limited. While some ETEC are clearly associated with development of cholera- like diarrhea, basic molecular mechanisms underlying severe illness remain undefined. The long-term goal of these studies is to address basic questions that can inform our understanding of acute illness and more chronic sequelae that may impact or approach to development of vaccines for these organisms:  “Why are individuals with blood group A more susceptible to severe infections cause by ETEC ?”  “How does ETEC or its toxins alter intestinal surfaces to promote infection?”  “Are ETEC particularly well-equipped to promote these interactions?”  “Are there other antigens that interact with host cells to promote infections?” Studies to date have shown us that the pathogenesis of ETEC infection is actually quite complicated, potentially involving many proteins. Novel proteins that are not part of vaccines currently being tested could be added to improve the coverage and function of these vaccines. Understanding disease susceptibility on a molecular level can permit us to protect individuals at the highest risk. Addressing these fundamental questions will fill important gaps in our understanding of ETEC interactions with the intestine as well as cellular responses that develop following ETEC infections. Collectively these studies should permit a more rational approach to development of a broadly protective vaccine for these pathogens of global importance.

项目总结/摘要 这项工作的重点是产肠毒素大肠杆菌（ETEC），全球最常见的细菌原因， 严重的慢性病。这些疾病威胁着世界贫困地区许多儿童的生命， 卫生设施和清洁用水有限。虽然一些ETEC显然与霍乱的发展有关， 与腹泻一样，严重疾病的基本分子机制仍不清楚。的长期目标 这些研究是为了解决一些基本问题，这些问题可以帮助我们了解急性疾病， 可能影响或接近这些微生物疫苗开发的慢性后遗症： 为什么A型血的人更容易受到ETEC引起的严重感染？ ETEC或其毒素如何改变肠道表面以促进感染？ ETEC是否特别有能力促进这些互动？ “是否有其他抗原与宿主细胞相互作用以促进感染？” 迄今为止的研究表明，ETEC感染的发病机制实际上相当复杂， 可能涉及许多蛋白质。目前正在测试的疫苗中没有的新蛋白质可能会被用于 以提高这些疫苗的覆盖率和功能。了解疾病易感性 分子水平的保护可以使我们保护处于最高风险的个人。 解决这些基本问题将填补我们对ETEC相互作用的理解中的重要空白， 肠道以及ETEC感染后产生的细胞反应。总体而言， 应该允许更合理的方法来开发针对这些病原体的广泛保护性疫苗， 全球重要性。