Optimization of protective antibodies response against bacterial adhesins

点击翻译按钮获取中文摘要

ABSTRACT The primary goal of this proposal is to understand how conformational properties of the major pathogenesis factor of E. coli - most common, type 1 fimbrial adhesin of E. coli - defines its ability to elicit a protective antibody response as a vaccine candidate against urinary tract infections caused by E. coli. FimH is an adhesive subunit of the type 1 fimbriae and is one of the major factors in the ability of E. coli to bing human urothelium and 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, bind fast and strongly human cell receptors and shed bound antibodies. We intend to perform a comprehensive functional analysis of antibodies against both conformational states of FimH to analyze the conformational switch in FimH in the context of the immune response against the adhesive protein.