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.
The primary goal of this proposal is to understand how the ability of most common Escherichia coli adhesin, FimH, to dynamically change its structure is affecting the type of antibodies that are produced against it. We intend to perform a comprehensive analysis of the molecular and protective properties of the antibodies in context of the their specificity and inhibition of the bacterial cell adhesion and pathogenicity.
|Kisiela, Dagmara I; Avagyan, Hovhannes; Friend, Della et al. (2015) Inhibition and Reversal of Microbial Attachment by an Antibody with Parasteric Activity against the FimH Adhesin of Uropathogenic E. coli. PLoS Pathog 11:e1004857|
|Kisiela, Dagmara I; Rodriguez, Victoria B; Tchesnokova, Veronika et al. (2013) Conformational inactivation induces immunogenicity of the receptor-binding pocket of a bacterial adhesin. Proc Natl Acad Sci U S A 110:19089-94|