Pathogenesis of EAST1 toxin in ETEC associated diarrhea disease

EAST1 毒素在 ETEC 相关腹泻病中的发病机制

基本信息

批准号：
7363893
负责人：
WEIPING ZHANG
金额：
$ 21.68万
依托单位：
SOUTH DAKOTA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-18 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7363893
关键词：
Accounting Address Affect Animals Antibiotic Resistance Bacteria Bacterial Adhesins Biological Biological Assay Biological Models Businesses Cessation of life Companions Data Development Diarrhea Disease Disease Outbreaks Economics Elderly Enterotoxins Escherichia coli Escherichia coli heat-labile toxin Exhibits Facility Construction Funding Category Family suidae Fimbria of hippocampus Genes Gnotobiotic Goals Health Heating High Prevalence Human Immunocompromised Host Individual Industry International Livestock Medial Military Personnel Modeling Mus National Institute of Allergy and Infectious Disease Neonatal Oryctolagus cuniculus Outcome Outcome Study Pathogenesis Physiological Pilum Population Prevention Prevention strategy Production Recruitment Activity Research Research Methodology Severities Students Sus scrofa System Testing Toxin Training Vaccines Virulence Virulence Factors Weaning base disorder control disorder prevention enteroaggregative Escherichia coli enterotoxigenic Escherichia coli heat stable toxin (E coli)pathogen prevent receptor research study therapy development

项目摘要

DESCRIPTION (provided by applicant): Enterotoxigenic Escherichia coli (ETEC) strains are categorized as priority B pathogens by NIAID. ETEC-associated diarrhea is responsible for nearly one million deaths each year around the world in addition to causing of illness to immunocompromised individuals and travelers including deployed military personnel. The key virulence factors in ETEC- associated diarrhea are believed to be bacterial adhesins or colonization factors (CFAs) and enterotoxins. Enteroaggregative Escherichia coli heat stable enterotoxin 1 (EAST1) is among the enterotoxins produced by E. coli strains that cause diarrhea in humans and animals. However, the virulence significance of EAST1 in diarrhea has not been defined, in part because a suitable model for key tests has not been identified. Results from our initial studies demonstrated that an additive model using K88ac-receptor positive gnotobiotic piglets and K88ac-fimbrial E. coli model can be readily employed to assess virulence significance of enterotoxins in E. coli-associated diarrhea. In this proposal, we will construct model pathogens expressing EAST1 toxin and K88ac fimbria to define virulence significance of EAST1 in diarrhea and its synergetic contribution to diarrhea caused by E. coli strains that also express other toxins by using the additive piglet challenge model. Determination of EAST1 virulence will provide information for the development of prevention and treatment strategies to protect humans and animals from diarrhea disease. This R15 proposal will recruit promising undergraduate students to be trained with the expert research team as they focus on the biological relevance of EAST1 toxin in diarrhea. Enterotoxigenic Escherichia coli (ETEC) are the primary cause of diarrheal disease. ETEC diarrhea is responsible for 400,000 to 800,000 deaths each year, and brings health concerns and economic consequences in international travelers and military personnel. Enteroaggregative Escherichia coli heat stable toxin 1 (EAST1) is associated with diarrhea. But whether EAST1 toxin is the virulence determinant in diarrhea is unclear. Determination of virulence significance of EAST1 is essential for us to identify other unknown virulence factors in diarrhea. This proposed research is to examine the virulence significance EAST1 in diarrhea. The determination of virulence significance of EAST1 toxin in diarrheal disease will provide essential information to prevent or control this disease.

描述（由申请人提供）：肠毒素大肠杆菌（ETEC）菌株被NIAID归类为优先B病原体。与ETEC相关的腹泻还造成全球近一百万人死亡，除了使疾病造成免疫力低下的个人和旅行者，包括部署的军事人员。相关腹泻中的关键毒力因子被认为是细菌粘附素或定殖因子（CFA）和肠毒素。大肠杆菌肠毒素1（EAST1）是大肠杆菌菌株产生的肠毒素之一，在人类和动物中引起腹泻。然而，尚未定义East1在腹泻中的毒力意义，部分原因是尚未确定合适的钥匙测试模型。我们最初的研究的结果表明，使用K88AC受体阳性Gnotobiotic Piglets和K88AC-脑大肠杆菌模型的加性模型很容易被用来评估肠毒素在大肠杆菌相关腹泻中的毒力意义。在该提案中，我们将构建表达East1毒素和K88AC纤维的模型病原体，以定义East1在腹泻中的毒力意义及其对大肠杆菌菌株引起的腹泻的协同贡献，这些大肠菌菌株也通过使用添加性小猪挑战模型来表达其他毒素。 EAST1毒力的确定将为预防和治疗策略的发展提供信息，以保护人类和动物免受腹泻病的侵害。该R15提案将招募有希望的本科生接受专家研究团队的培训，因为他们专注于East1毒素在腹泻的生物学相关性。肠毒素大肠杆菌（ETEC）是腹泻病的主要原因。 ETEC腹泻每年造成400,000至800,000人死亡，并对国际旅行者和军事人员带来健康问题和经济后果。肠凝集大肠杆菌热稳定毒素1（EAST1）与腹泻有关。但是，East1毒素是否是腹泻中的毒力决定因素尚不清楚。 EAST1的毒力意义的确定对于我们确定腹泻中其他未知的毒力因子至关重要。这项拟议的研究是检查腹泻中的毒力显着性East1。 East1毒素在腹泻病中的毒力意义的确定将提供预防或控制这种疾病的重要信息。