Quercetin, A Potential Metallo-β-Lactamase Inhibitor for Use in Combination Therapy Against β-Lactam Antibiotic-Resistant Bacteria

Among the various mechanisms that bacteria use to develop antibiotic resistance, the multiple expression of β-lactamases has become pandemic, threatening public health and increasing patient mortality rates. Although combination therapy—in which a β-lactamase inhibitor is administered together with a β-lactam antibiotic—has proven effective against serine β-lactamases, inhibitors are not yet available for metallo-β- lactamases. Herein, we describe the potential for quercetin, a plant-derived flavinol, to be utilized in combination therapy as a metallo-β-lactamase inhibitor. Previous studies have demonstrated the numerous biological effects that this natural compound may exhibit; however, its anti-bacterial and inhibitor activity is only now coming under investigation. We therefore seek to provide an overview of the literature describing the current progress in our understanding of quercetin as a metal-chelator and a β-lactamase inhibitor and thus bring greater attention to this non-toxic and abundant natural product.

Keywords: Quercetin; Flavinols; Anti-Microbials; Combination Therapy; Metallo-β-Lactamase Inhibitor

Abbreviation: AMA: Aspergillo Marasmine A; EDTA: Ethylene Diaminetetraacetic acid; ESKAPE: Enterococcus Faecium, Staphylococcus Aureus, Klebsiella Pneumoniae, Acinetobacter Baumannii, Pseudomonas Aeruginosa, and Enterobacter Species; FDA: Food and Drug Administration; IMP: Imipenemase; MBL: Metallo-β-Lactamase; NDM-1: New Delhi Metallo-Beta-Lactamase-1; VIM: Verona Imipenemase