Dissecting the role of fimbrial repertoire in Enteroaggregative Escherichia coli

剖析菌毛在肠聚集性大肠杆菌中的作用

• 批准号: 8823332
• 负责人: JORGE A GIRON
• 金额: $ 23.7万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-20 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8823332
• 关键词: 5 year old; Accounting; Acute; Adherence; Adhesives; Agriculture; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Antibody Response; Area; Bacteria; Biological; Cell Communication; Cells; Characteristics; Child; Childhood; Consumption; Data; Developed Countries; Developing Countries; Development; Diarrhea; Disease; Disease Outbreaks; Epithelial Cells; Escherichia coli; Escherichia coli EHEC; Escherichia coli Infections; Fimbriae Proteins; Fimbrial Adhesins; Fimbrin; Food; Foundations; Future; Genes; Geographic Locations; Goals; Health; Human; Immune response; Infection; Infection prevention; Inflammatory; Inflammatory Response; Intestines; Kidney; Knowledge; Laboratories; Life; Life Style; Link; Lipoproteins; Membrane; Meningitis; Microbial Biofilms; Molecular; Molecular Chaperones; Northern Europe; Operon; Organism; Patients; Pattern; Pilum; Play; Population; Prevention; Property; Proteins; Public Health; Reporting; Research; Role; Salmonella; Septicemia; Serum; Shiga Toxin; Surface; United States National Institutes of Health; Virulence; Virulence Factors; Water; World Health; analog; appendage; beef; cytokine; differential expression; enteroaggregative Escherichia coli; enteropathogenic Escherichia coli; fimbria; gastrointestinal infection; insight; mortality; mucoid; novel; pathogen; pathogenic Escherichia coli; prevent; public health relevance; receptor; tool; trait

 DESCRIPTION (provided by applicant): Diarrheal diseases account for 650 million cases per year worldwide and 6 million children under 5 years old die each year due to acute gastrointestinal infection. Several pathotypes of diarrheagenic Escherichia coli [enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC)] play a major etiologic role in endemic areas. Enterohemorrhagic E. coli (EHEC) are associated with serious intestinal and kidney illness in developed countries due to consumption of tainted beef and agricultural products. The recent outbreaks caused in Northern Europe by a new EAEC O104:H4 producing the Shiga toxin highlight undoubtedly the significance of pathogenic E. coli and their ability to acquire virulence factors. The EAEC pathotype comprises a group of highly heterogenous E. coli strains, which share in common the ability to aggregate onto abiotic surfaces and epithelial cells forming a characteristic stacked-brick pattern. Their capacity to form dense biofilms may explain in part their ability to cause persistent diarrhea. Three aggregative adherence fimbriae (AAF/I-III) have been reported in EAEC but these are present in less than 15% of strains from different geographic regions. However, many other fimbrial operons exist that are shared with comnesal E. coli strains but little is known regarding their rol in adherence and biofilm formation. In this project we will provide insight into better understand the differential expression of these fimbrial operons and how they relate to adherence and biofilm formation. We expect to advance knowledge on the virulence mechanisms of pathogenic E. coli in general for the development of strategies towards prevention and treatment of diarrheal illnesses.

 描述（由申请人提供）：全世界每年有6.5亿例腹泻病，每年有600万5岁以下儿童死于急性胃肠道感染。致病性大肠杆菌的几种致病型[肠致病性（EPEC）、肠聚集性（EAEC）、肠致病性（ETEC）]在流行区起主要的病原作用。肠出血性大肠在发达国家，由于食用受污染的牛肉和农产品，大肠杆菌（EHEC）与严重的肠道和肾脏疾病有关。最近在北方欧洲由一种新的产滋贺毒素的EAEC O 104：H4引起的疫情无疑突出了致病性E.大肠杆菌及其获得毒力因子的能力。 EAEC致病型包括一组高度异质的E.大肠杆菌菌株，它们共同具有聚集在非生物表面和上皮细胞上形成特征性堆叠砖状图案的能力。它们形成致密生物膜的能力可以部分解释它们引起持续腹泻的能力。在EAEC中已经报道了三种聚集性粘附菌毛（AAF/I-III），但这些菌毛存在于来自不同地理区域的不到15%的菌株中。然而，存在许多与comnesal E.大肠杆菌菌株，但很少知道他们的作用，粘附和生物膜的形成。在这个项目中，我们将提供更好地了解这些菌毛操纵子的差异表达，以及它们如何与粘附和生物膜形成。我们希望能进一步了解致病性大肠杆菌的致病机制。大肠杆菌的一般发展战略，以预防和治疗肠道疾病。