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Metallo-beta-lactamases (MBLs) are a diverse group of enzymes that confer resistance to a broad spectrum of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. They catalyze the hydrolysis of the beta-lactam ring, rendering these antibiotics ineffective. MBLs are particularly concerning due to their ability to inactivate carbapenems—often considered last-resort antibiotics—and the absence of clinically available inhibitors. They are classified into subgroups B1, B2, and B3, all sharing an αβ/βα sandwich fold and typically requiring one or two zinc ions for activity. MBLs provide bacteria with high-level resistance, and their genes spread rapidly via horizontal gene transfer. The New Delhi metallo-beta-lactamase 1 (NDM-1) is a notable example implicated in global outbreaks of multidrug-resistant infections.
Zinc-dependent hydrolysis of beta-lactam ring
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