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The emergence and spread of carbapenemase in Gram-negative pathogens poses an enormous threat to global public health. New Delhi metallo-β-lactamase-1 (NDM-1) inactivates nearly every class of β-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 β-lactamase NDM-1. The IC 50  of embelin was 2.1 ± 0.2 μM 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 Zn 2+ , 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.

Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens