NMR Backbone Assignment of VIM-2 and Identification of the Active Enantiomer of a Potential Inhibitor

Carbapenem resistance caused by metallo-β-lactamases is a serious global challenge that, if not tackled efficiently, expected to lead millions of deaths in the coming decades. Verona-integron encoded metallo-β-lactamase 2 (VIM-2) bacterial enzyme that has been reported from multidrug-resistant nosocomial isolates Pseudomonas aeruginosa and other Gram-negative pathogens. As it hydrolyzes most β-lactams including carbapenems, major threat current antimicrobial chemotherapies. So far, there no clinically applicable inhibitor for this enzyme. In work, backbone NMR resonance assignment VIM-2 disclosed, opening up investigations important its potential inhibitors solutions, enabling rational improvement candidates. Making use assignment, we identified active enantiomer candidate as well possible binding site Kd, utilizing chemical shift titration experiments.