The Bacterial Lectin FimH, a Target for Drug Discovery - Carbohydrate Inhibitors of Type 1 Fimbriae-Mediated Bacterial Adhesion

Adhesion is a prerequisite for bacteria to colonize cell surfaces. To accomplish cellular adhesion, many bacteria use carbohydrate-specific lectins, which are expressed as part of capillary protein appendages expanding from their surface, called fimbriae or pili. For bacteria, colonization of cell surfaces offers advantageous conditions to persist and multiply. For the host, however, bacterial colonization can be affiliated with severe health problems such as inflammation. Therefore, to combat bacterial adhesion and inflammatory diseases, investigation of the molecular and biophysical details of the relevant lectin-carbohydrate interactions is important. Understanding molecular carbohydrate recognition can lead to the development of high-affinity inhibitors of bacterial lectins. That way, interfering with the bacterial attachment to surfaces proves the vision of an antiadhesion therapy, among others, against uropathogenic E. coli (UPEC). One of the most important and best investigated bacterial lectins is the mannose-specific protein FimH, which is expressed on the tips of type 1 fimbriae. During the last 30 years, many natural as well as synthetic mannosidic ligands of FimH have been designed and tested for their inhibitory potencies. We report key results and comment on key problems and perspectives of this research.