No abstract

Because of the antimicrobial resistance crisis,lectins are considered novel drug targets.P seudomonas aeruginosa utilizes LecA and LecB in the infection process.I nhibition of both lectins with carbohydrate-derived molecules can reduce biofilm formation to restore antimicrobial susceptibility.Here, we focused on non-carbohydrate inhibitors for LecA to explore new avenues for lectin inhibition. From as creening cascade we obtained one experimentally confirmed hit, ac atechol, belonging to the well-known PAINS compounds. Rigorous analyses validated electron-deficient catechols as millimolar LecA inhibitors.T he first co-crystal structure of anon-carbohydrate inhibitor in complex with abacterial lectin clearly demonstrates the catechol mimicking the binding of natural glycosides with LecA. Importantly,c atechol 3 is the first non-carbohydrate lectin ligand that binds bacterial and mammalian calcium(II)-binding lectins,g iving rise to this fundamentally new class of glycomimetics.