Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, the authors provide for the first time binding data of the mol. events underlying type 1 fimbrial adherence, by crystallog. analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl mannosides. The results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous Bu a-D-mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (Kd = 0.15 mM) than mannose (Kd = 2.3 mM). Exploration of the binding affinities of a-D-mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold redn. in affinity, resp., compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concns. of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. The authors foresee that the authors' findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs. [on SciFinder (R)]