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）：产肠毒素大肠杆菌 (ETEC) 菌株被 NIAID 归类为优先 B 病原体。 ETEC 相关腹泻每年导致全世界近一百万人死亡，此外还导致免疫功能低下的个人和旅行者（包括部署的军事人员）患病。 ETEC 相关腹泻的关键毒力因子被认为是细菌粘附素或定植因子 (CFA) 和肠毒素。肠聚集性大肠杆菌热稳定肠毒素 1 (EAST1) 是由大肠杆菌菌株产生的肠毒素之一，可引起人类和动物腹泻。然而，EAST1 在腹泻中的毒力意义尚未确定，部分原因是尚未确定适合关键测试的模型。我们初步研究的结果表明，使用 K88ac 受体阳性无菌仔猪和 K88ac 菌毛大肠杆菌模型的附加模型可以很容易地用于评估肠毒素在大肠杆菌相关腹泻中的毒力意义。在本提案中，我们将构建表达 EAST1 毒素和 K88ac 菌毛的模型病原体，以通过使用附加仔猪攻击模型来定义 EAST1 在腹泻中的毒力意义及其对也表达其他毒素的大肠杆菌菌株引起的腹泻的协同作用。 EAST1毒力的测定将为制定预防和治疗策略以保护人类和动物免受腹泻病提供信息。该 R15 提案将招募有前途的本科生与专家研究团队一起接受培训，因为他们专注于 EAST1 毒素在腹泻中的生物学相关性。产肠毒素大肠杆菌 (ETEC) 是腹泻病的主要原因。 ETEC 腹泻每年导致 400,000 至 800,000 人死亡，并给国际旅行者和军事人员带来健康问题和经济后果。肠聚集性大肠杆菌热稳定毒素 1 (EAST1) 与腹泻有关。但 EAST1 毒素是否是腹泻的毒力决定因素尚不清楚。确定 EAST1 的毒力意义对于我们识别腹泻中其他未知的毒力因子至关重要。本研究旨在检验 EAST1 在腹泻中的毒力意义。确定EAST1毒素在腹泻病中的毒力意义将为预防或控制该疾病提供重要信息。