Drug resistance is becoming a rising problem worldwide that led to more than 700 000 deaths last year. The opportunistic ESKAPE pathogen Pseudomonas aeruginosa is considered as particularly critical by the World Health Organization (WHO). Different approaches for treatment are currently being investigated and the inhibition of their adhesins to prevent bacterial biofilm formation is a promising approach to break antimicrobial resistance.[1,2] Biofilms protect the bacteria from external threats such as antibiotics and immune defense and are therefore a target for intervention.[3] P. aeruginosa expresses two lectins, D-galactose binding LecA and L-fucose/ D-mannose binding LecB, which are both virulence factors and responsible for bacterial adhesion and biofilm formation. It was shown that inhibition of these lectins with carbohydrate-derived molecules leads to a reduced biofilm formation. Here, we aimed at the development of non-carbohydrate glycomimetics targeting LecA. To this end, we identified catechols as potential LecA inhibitors, and carefully validated these well-known pan assay interference class of molecules in biophysical assays. Competitive binding was established for a distinct set of catechol containing molecules.
