Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic <i>Escherichia coli</i>
Georgia I. Nasi,
Konstantina I. Georgakopoulou,
Marilena K. Theodoropoulou,
Nikos C. Papandreou,
Evangelia D. Chrysina,
Paraskevi L. Tsiolaki,
Vassiliki A. Iconomidou
Affiliations
Georgia I. Nasi
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
Konstantina I. Georgakopoulou
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
Marilena K. Theodoropoulou
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
Nikos C. Papandreou
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
Evangelia D. Chrysina
Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
Paraskevi L. Tsiolaki
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
Vassiliki A. Iconomidou
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15701 Athens, Greece
Type I fimbriae are the main adhesive organelles of uropathogenic Escherichia coli (UPEC), consisting of four different subunits. Their component with the most important role in establishing bacterial infections is the FimH adhesin located at the fimbrial tip. This two-domain protein mediates adhesion to host epithelial cells through interaction with terminal mannoses on epithelial glycoproteins. Here, we propose that the amyloidogenic potential of FimH can be exploited for the development of therapeutic agents against Urinary Tract Infections (UTIs). Aggregation-prone regions (APRs) were identified via computational methods, and peptide-analogues corresponding to FimH lectin domain APRs were chemically synthesized and studied with the aid of both biophysical experimental techniques and molecular dynamic simulations. Our findings indicate that these peptide-analogues offer a promising set of antimicrobial candidate molecules since they can either interfere with the folding process of FimH or compete for the mannose-binding pocket.