Aromatic alpha-glycosides of mannose are powerful inhibitors of the adherence of type 1 fimbriated Escherichia coli to yeast and intestinal epithelial cells

Abstract

Adherence of bacteria via their surface lectins to host epithelial cells is considered an important initial event in bacterial pathogenesis. Mannose-specific (type 1) fimbriae are among the most commonly found lectins in enterobacteria. We studied the effect of aromatic α-glucosides of mannose on the agglutination of mannan-containing yeasts by different strains of Escherichia coli and on the adherence of the bacteria to guinea pig ileal epithelial cells. In both systems these compounds were considerably more effective inhibitors than methyl α-mannoside, with 4-methylumbelliferyl α-mannoside and p-nitro-o-chlorophenyl α-mannoside being the strongest inhibitors. Both compounds were approximately 400-times stronger inhibitors of yeast agglutination by E. coli O128 than was methyl α-mannoside and 1,000- and 470-fold stronger, respectively, than was methyl α-mannoside in inhibiting the adherence of the bacteria to ileal epithelial cells. 4-Methylumbelliferyl α-mannoside was 540 to 1,000 times more effective in inhibiting yeast agglutination by four additional strains of mannose-specific E. coli. It was also more efficient than methyl α-mannoside in removing adherent E. coli O128 from ileal epithelial cells. Our resuls provide further evidence that type 1 fimbriae of E. coli possess a hydrophobic region next to the mannose-binding site. The results suggest that 4-methylumbelliferyl α-mannoside and p-nitro-o-chlorophenyl α-mannoside are good candidates for the design of therapeutic agents that may prevent adherence in vivo and infection by E. coli strains that express type 1 fimbriae.