Recent Advances in the Discovery of Metallo-β-Lactamase Inhibitors for β-lactam Antibiotic-Resistant Reversing Agents

The overuse of antibiotics which exerts the selective pressure for bacterial pathogens has facilitated the spread of antibiotics' resistance. Metallo-beta-lactamases (M beta Ls) are zinc enzymes produced by an increasing number of bacterial pathogens. They can readily cleave carbapenems and most other beta-lactams that are mainstays of therapy for bacterial infections. M beta L-conferred resistance to antibiotics is most worrisome due to M beta Ls exhibiting very broad-spectrum resistance. Therefore, the bacteria carrying M beta Ls have recently become a significant clinical threat. No clinically useful M beta Ls inhibitor has been discovered yet. To address the serious threat to public health posed by the M beta L-conferred resistance to antibiotics, novel effective M beta L inhibitors are urgently needed. This review mainly describes various M beta L inhibitors, giving special attention to their antibacterial activity, mechanisms of action, structure-activity relationships and synergetic effect with clinically available antibiotics.