Abstract:
Carbohydrates play pivotal roles in the first stages of microbial infections and can be exploited as decoys to hijack the interactions between bacteria and the host cell. Multivalent glycan probes mimicking the natural presentation of glycans in living cells have been successfully employed to study fundamental carbohydrate/protein interactions in microbial systems; however, most pathogenic glycan receptors exhibit a shared specificity for commonly found sugars present in both healthy and pathogenic cells, posing a challenge for target selectivity. In this study, we report the synthesis of a small library of d-arabinose multivalent probes, a sugar absent in human physiology, and their evaluation in a bacteria agglutination assay using cluster analysis. Our findings reveal preferential binding to Staphylococcus aureus of C2-linked arabinose moieties over C1- or C5-linked probes, underscoring the importance of glycan presentation in targeting specificity. Furthermore, we demonstrate the selectivity of the C2-linked probe toward S. aureus across a panel of common bacterial pathogens. Additionally, these probes are able to disrupt biofilm formation in S. aureus SH1000, thereby further proving the cell surface interactions with S. aureus