Development of an additive model to study the significance of heat-labile and hea

开发加性模型来研究热不稳定和热的重要性

基本信息

批准号：
7235838
负责人：
WEIPING ZHANG
金额：
$ 7.18万
依托单位：
SOUTH DAKOTA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7235838
关键词：
Adhesions Animal Experimentation Animal Model Animals Antigens Area Bacteria Bacterial Adhesins Binding Biological Biological Models Cessation of life Child Clinical Dehydration Developing Countries Development Diarrhea Disease Disruption Employment Enteral Enterocytes Enterotoxins Escherichia coli Escherichia coli Vaccines Exhibits Family suidae Fimbria of hippocampus Fimbrial Adhesins Fluids and Secretions Future Gene Expression Genes Gnotobiotic Goals Hand Heating Homeostasis Human Human Development Human Volunteers Individual Infection Infectious Diseases Research Ingestion Inherited Intestines Liquid substance Livestock Mediating Military Personnel Modeling Morbidity - disease rate Mus Numbers Pathogenesis Pathogenicity Personal Satisfaction Pilum Plasmids Play Predisposition Process Proteins Relative (related person)Reporting Research Research Project Grants Resistance Risk Rodent Role Safety Severities Severity of illness Small Intestines Study models Surface Sus scrofa System Toxic effect Toxin Virulence Virulence Factors Virulent Weaning Wolves base design enterotoxigenic Escherichia coli enterotoxin ST enterotoxin STa enterotoxin STb experience human subject mortality mouse model neonate pathogen prevent prototype receptor research study response scorpion toxin I&apos &apos vaccine development volunteer

项目摘要

DESCRIPTION (provided by applicant): Enterotoxigenic Escherichia coli (ETEC) associated diarrheal disease are responsible for an estimated 400,000 to 800,000 deaths annually. Bacterial adhesins or colonization factors (CFAs) and enterotoxins are the key virulence factors in ETEC diarrhea. Enterotoxins, heat-labile toxin(LT) and heat stable toxins (STa, STb) are the main enterotoxins produced by ETEC, these toxins cause disruption of fluid homeostasis and stimulate fluid secretion, which results in diarrhea. However, very limited studies have been done to study virulence significance of individual enterotoxin and to identify enterotoxin(s) of virulence determinant in ETEC diarrhea, which might directly lag vaccine development using enterotoxin(s) as antigens to prevent or decrease the severity of diarrheal disease in humans. The major obstacle to study the pathogenicity of enterotoxins is the lack of a suitable challenge model. Human subject challenge studies have been very limited because of concerns of safety risk, ethnics, and financial expanses; while rodents, the preferred models of most infectious disease research, show no susceptibility to ETEC, and therefore have little value to study ETEC disease. In contrast, certain pigs are naturally susceptible to ETEC, and K88 fimbrial ETEC pathogens to which pigs are susceptible have been studied most extensively and their correlative relationships with diarrhea are best characterized. This research proposes to clone estAB, estA, and estB genes separately for expression of LT, STa and STb, and to construct model pathogens which will allow us to examine significance of each individual enterotoxin in diarrhea. The overall goal of this project is to develop a versatile model to examine the biological relevance of individual enterotoxin in diarrhea disease. The study will elucidate the roles of LT, STa and STb in ETEC diarrhea, and determine the key enterotoxins that may pave the way for development of human ETEC vaccines based on enterotoxins as antigens.

描述（由申请人提供）：产肠毒素大肠杆菌 (ETEC) 相关的腹泻病每年估计导致 400,000 至 800,000 人死亡。细菌粘附素或定植因子 (CFA) 和肠毒素是 ETEC 腹泻的关键毒力因子。肠毒素、不耐热毒素（LT）和热稳定性毒素（STa、STb）是ETEC产生的主要肠毒素，这些毒素会破坏体液稳态并刺激体液分泌，从而导致腹泻。然而，研究个别肠毒素的毒力意义和鉴定 ETEC 腹泻毒力决定因素的肠毒素的研究非常有限，这可能直接滞后于使用肠毒素作为抗原来预防或减轻腹泻严重程度的疫苗开发。人类疾病。研究肠毒素致病性的主要障碍是缺乏合适的攻击模型。由于对安全风险、种族和财务扩张的担忧，人类受试者挑战研究非常有限；而啮齿动物作为大多数传染病研究的首选模型，对 ETEC 不具有易感性，因此对 ETEC 疾病的研究价值不大。相比之下，某些猪天然对 ETEC 敏感，并且对猪易感的 K88 菌毛 ETEC 病原体进行了最广泛的研究，并且对它们与腹泻的相关关系进行了最好的表征。本研究拟分别克隆 estAB、estA 和 estB 基因以表达 LT、STa 和 STb，并构建模型病原体，使我们能够检查每种肠毒素在腹泻中的重要性。该项目的总体目标是开发一种通用模型来检查个体肠毒素在腹泻病中的生物学相关性。该研究将阐明LT、STa和STb在ETEC腹泻中的作用，并确定关键的肠毒素，这可能为开发基于肠毒素作为抗原的人类ETEC疫苗铺平道路。