Antigenic switch in bacterial adhesins

细菌粘附素的抗原转换

• 批准号: 8695287
• 负责人: EVGENI Veniaminovic SOKURENKO
• 金额: $ 19.31万
• 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/8695287
• 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）：本提案的主要目标是了解大肠杆菌最常见的1型菌毛粘附素的变构构象特性如何定义其在尿路感染发病机制中的作用。FimH是1型菌毛的粘附亚基，是大肠杆菌引起尿路感染的主要因素之一。我们确定了FimH的甘露糖结合凝集素结构域可以呈现两种构象状态-对终端暴露的甘露糖基残基具有高亲和力和低亲和力。FimH的构象变化本质上是高度动态的，是FimH介导剪切增强细菌粘附能力的基础。我们打算在免疫反应中分析FimH的构象开关。