Studies on Emergent Diarrheagenic E. coli Pathogens

突发性腹泻大肠杆菌的研究

• 批准号: 8597997
• 负责人: Oscar G GOMEZ
• 金额: $ 36.2万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-15 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8597997
• 关键词: 5 year old; Adherence; Animal Model; Antibiotic Resistance; Bacteriophages; Basic Science; Case-Control Studies; Categories; Cause of Death; Cells; Cessation of life; Child; Childhood; Chromosomes; Clinical; Clinical Sciences; Clonality; Collection; Colombia; Costa Rica; Country; DNA; DNA Sequence Analysis; Data; Developing Countries; Development; Diarrhea; Disease; Epidemiology; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Etiology; Event; Evolution; Feces; Frequencies; Future; Genes; Genetic; Genetic Markers; Genetic Materials; Genetic Variation; Genome; Goals; Horizontal Gene Transfer; Human; Incidence; Infection; International; Intestines; Knowledge; Latin America; Lesion; Life; Mediating; Modeling; Molecular; Molecular Biology; Molecular Epidemiology; Organism; Outcome; Pakistan; Pathogenesis; Pathogenicity; Pathogenicity Island; Phenotype; Pilum; Plasmids; Prevalence; Prevention; Prevention Measures; Prevention strategy; Public Health; Research; Role; Rotavirus; Secondary to; South America; South Dakota; Testing; Type III Secretion System Pathway; Universities; Vaccines; Viral; Virulence; Virulence Factors; Work; base; cytotoxicity; enteropathogenic Escherichia coli; enterotoxigenic Escherichia coli; epidemiology study; genetic element; genetic epidemiology; innovation; insight; medical schools; mortality; novel; pathogen; pathogenic bacteria; pilus genes; public health relevance; research and development; surveillance study; tool; vaccine development

DESCRIPTION (provided by applicant): Childhood diarrhea leads to 2 million deaths every year among children less than 5 years of age mainly in underserved countries. E. coli pathogens are believed to be the second most common cause of death after Rotavirus. Six categories of diarrheagenic E. coli have been known to cause diarrhea, yet, recent studies by our group have identified a new diarrheagenic category designated localized adherent E. coli (LAEC) that is significantly associated with childhood diarrhea in Colombia, South America. The long term goal of this study is to understand the epidemiology and the molecular mechanisms of pathogenesis of this new LAEC emergent pathogen. The first specific aim proposes to evaluate the frequency and association of LAEC with childhood diarrhea by conducting two international multicenter case-control studies. We hypothesize that LAEC is associated with childhood diarrhea in children less than 5 years of age living in developing countries. The second specific aim will explain how LAEC virulence factors are essential to cause disease in a piglet model of human infection. We hypothesize that the type IV bundle-forming pilus and a novel type III secretion system directing bacterial-cell invasion are directly associated with the pathogenesis of LAEC diarrhea. The last specific aim will conduct genome DNA sequencing analysis of LAEC strains to identify the genetic elements that resulted in the emergence of LAEC as a pathogen. We hypothesize that LAEC shares in common well defined virulence genes that were acquired by horizontal gene transfer. This project if significant because it will bring fundamental knowledge on the epidemiology, genetics, and pathogenesis of LAEC and will generate molecular biology tools to facilitate future studies on LAEC diarrhea epidemiology, prevention measures and vaccine development research.

描述（由申请人提供）：儿童腹泻每年导致200万5岁以下儿童死亡，主要发生在服务不足的国家。E.大肠杆菌病原体被认为是仅次于轮状病毒的第二大常见死因。6种常见的致菌E.已知大肠杆菌会引起腹泻，然而，我们小组最近的研究已经确定了一种新的肠源性类别，称为局部粘附性大肠杆菌。大肠杆菌（LAEC）与南美哥伦比亚的儿童腹泻显著相关。本研究的长期目标是了解这种新的LAEC突发病原体的流行病学和发病机制的分子机制。第一个具体目标是通过进行两项国际多中心病例对照研究来评估LAEC与儿童腹泻的频率和相关性。我们假设LAEC与生活在发展中国家的5岁以下儿童的儿童腹泻有关。第二个具体目标将解释LAEC毒力因子是如何在人类感染的仔猪模型中引起疾病的。我们推测，IV型菌毛形成菌毛和一种新的III型分泌系统直接指导细菌细胞入侵LAEC腹泻的发病机制。最后一个具体目标是对LAEC菌株进行基因组DNA测序分析，以确定导致LAEC作为病原体出现的遗传因素。我们假设LAEC共享通过水平基因转移获得的共同的明确定义的毒力基因。该项目意义重大，因为它将带来LAEC流行病学，遗传学和发病机制的基础知识，并将产生分子生物学工具，以促进LAEC腹泻流行病学，预防措施和疫苗开发研究的未来研究。