Antigenic switch in bacterial adhesins

细菌粘附素的抗原转换

• 批准号: 8588239
• 负责人: EVGENI Veniaminovic SOKURENKO
• 金额: $ 21.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-05 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588239
• 关键词: Adhesions; Adhesives; Affect; Affinity; Antibodies; Antibody Formation; Antigenic Switching; Antigens; Back; Bacteria; Bacterial Adhesins; Bacterial Adhesion; Binding; Cell Adhesion; Cell surface; Docking; Escherichia coli; Escherichia coli Adhesins; Escherichia coli Infections; Exhibits; Fimbriae Proteins; Fimbrial Adhesins; Goals; Immune response; Lectin; Ligands; Mannose; Mannose Binding Lectin; Mannose-Binding Lectins; Mechanics; Mediating; Molecular; Molecular Analysis; Molecular Conformation; Monoclonal Antibodies; Nature; Pathogenesis; Pathogenicity; Physiological; Property; Proteins; Research; Role; Specificity; Structure; Surface; Time; Urinary tract infection; Uropathogenic E. coli; Vaccines; Variant; Virulence Factors; base; novel strategies; polyclonal antibody; prevent; public health relevance; receptor; response; type 1 fimbriae; vaccine candidate

DESCRIPTION (provided by applicant): The primary goal of this proposal is to understand how allosteric conformational properties of the most common, type 1 fimbrial adhesin of E. coli defines its role in the pathogenesis of urinary tract infections. FimH is an adhesive subunit of th type 1 fimbriae and is one of the major factors in the ability of E. coli to cause urinary tract infection. We determined that the mannose-binding lectin domain of FimH can assume two conformational states - with a high- and low-affinity towards terminally-exposed mannosyl residues. The conformational shift in FimH is highly dynamic in nature and is the basis of the ability of FimH to mediate shear-enhanced bacterial adhesion. We intend to analyze the conformational switch in FimH in the context of the immune response against the adhesive protein.

描述（由申请人提供）：该提案的主要目标是了解大肠杆菌最常见的1型纤维化粘附蛋白的变构构象特性如何定义其在尿路感染的发病机理中的作用。 FIMH是1型纤维化的粘合剂亚基，是大肠杆菌引起尿路感染能力的主要因素之一。我们确定FIMH的甘露糖结合凝集素结构域可以假设两个构象状态 - 对末端暴露的甘露糖基残基具有高亲和力。 FIMH的构象转移本质上是高度动态的，是FIMH介导剪切增强细菌粘附的能力的基础。我们打算在针对粘合蛋白的免疫反应的背景下分析FIMH中的构象开关。