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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要这项工作重点关注产肠毒素大肠杆菌 (ETEC)，它是全球范围内最常见的细菌性致病菌这些疾病威胁着世界贫困地区许多儿童的生命。尽管某些 ETEC 明显与霍乱的发生有关，但卫生设施和清洁水却很有限。与腹泻一样，严重疾病的基本分子机制仍不清楚。这些研究旨在解决可以帮助我们了解急性疾病等的基本问题可能影响或接近这些生物体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？” “是否还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，可能涉及许多不属于目前正在测试的疫苗的蛋白质。添加以提高这些疫苗的覆盖范围和功能。分子水平可以让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 与这些研究共同探讨了 ETEC 感染后肠道和细胞的反应。应允许采取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。