Inhibition of bacterial adhesion to live human cells: Activity and cytotoxicity of synthetic mannosides

Bacterial adhesion to glycosylated surfaces is a key issue in human health and disease. Inhibition of bacterial adhesion by suitable carbohydrates could lead to an anti-adhesion therapy as a novel approach against bacterial infections. A selection of five α-mannosides has been evaluated as inhibitors of bacterial adhesion to the polysaccharide mannan, as well as to the surface of live human HT-29 cells. Cell toxicity studies were performed to identify the therapeutic window for a potential in vivo-application of the tested carbohydrates. A previously published mannosidic squaric acid diamide was shown to be exceptionally effective as inhibitor of the bacterial lectin FimH.

► Bacterial adhesion to human cells and its inhibition with new mannosides was shown.
► We conclude that mannan is a fair model for highly mannosylated cell surfaces.
► Cytotoxicity of tested mannosides was determined and the biocompatibility indices determined.
► A novel mannosidic squaric acid derivative was identified as new lead compound.
► The glycobiological potential of specific mannosides for an anti-adhesion approach was shown.