Antigenic switch in bacterial adhesins

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。大肠杆菌确定了其在尿路感染发病机制中的作用。FimH是Th 1型菌毛的粘附亚基，是影响E.大肠杆菌引起尿路感染。我们确定，甘露糖结合凝集素结构域的FimH可以采取两种构象状态-具有高和低亲和力对终端暴露的甘露糖残基。FimH中的构象转变本质上是高度动态的，并且是FimH介导剪切增强的细菌粘附的能力的基础。我们打算分析FimH中的构象开关的背景下，对粘附蛋白的免疫反应。

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.