Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens.

The emergence and spread of carbapenemase in Gram-negative pathogens poses an enormous threat to global public health. New Delhi metallo-beta-lactamase-1 (NDM-1) inactivates nearly every class of beta-lactam antibiotics, including carbapenem; however, there is no clinically useful NDM-1 inhibitor. Embelin, an important ingredient in traditional herbal medicine, has anti-tumor effects. The current study is the first to discover and examine the inhibitory activity of embelin against beta-lactamase NDM-1. The IC50 of embelin was 2.1 +/- 0.2 mu M when tested against NDM-1 carbapenemase. Most regions of the embelin molecule were buried within NDM-1's active site, and the hydroxyl group of embelin interacted directly with the metal ion Zn2+ as shown by molecular dynamic simulation. Systematic analysis of the antibacterial activities of embelin and antibiotics demonstrated that embelin restored meropenem activity against a panel of NDM-positive pathogens, such as Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Based on these results, embelin could be a promising carbapenem adjuvant candidate against NDM-1-producing bacterial strains.