Abstract

In recent work, we have used chemical screening to identify inhibitor hits that would block trimeric autotransporter adhesins from binding to collagen. To this end, we have developed screening assays where the adhesin in question is expressed on the E.coli cell surface. The bacteria expressing the recombinant adhesin are then fluorescently labeled and exposed to a collagen-coated surface. During screening, chemicals from a >40.000 compound library have been added to this setup, and a loss of fluorescence was interpreted as effective adhesion inhibition. After eliminating false positives such as fluorescence quenchers or bactericidal substances, we were left with <20 hits that had promising properties and that we now study further. I will show some of the results on dose-dependent inhibition, and discuss possible uses of such inhibitors as therapeutics, implant coatings or research tools.