Arrays of Self-Assembled Monolayers for Studying Inhibition of Bacterial Adhesion

This paper describes a simple and convenient method for the rapid screening of potential inhibitors of bacterial adhesion and for the quantitative evaluation of the efficacy of the inhibitors using arrays of self-assembled monolayers (SAMs) of alkanethiolates on gold that are presented on a 96-well microtiter plate. The SAMs present mixtures of α-d-mannopyranoside (a ligand that promotes the adhesion of uropathogenic Escherichia coli by binding to the FimH proteins on the tip of type 1 pili), and tri(ethylene glycol) moieties (organic groups that resist nonspecific adsorption of proteins and cells). The SAMs provide surfaces for studies of adhesion of uropathogenic E. coli to specific ligands; they also provide excellent resistance to nonspecific adhesion. Using arrays of mannoside-presenting SAMs, inhibitors of bacterial adhesion were easily screened by observing the number of bacteria that adhered to the surface of the SAMs in the presence of inhibitor. The potency of the inhibitor was quantified by measuring the percentage of inhibition as a function of the concentration of the inhibitor. The properties of SAMs, when combined with the convenience and standardization of a microtiter plate, make arrays of SAMs a versatile tool that can be applied to high-throughput screening of inhibitors of bacterial, viral, and mammalian cell adhesion and of strongly binding ligands for proteins.