Ambler class B metallo-β-lactamase (MBL)

Ambler class B metallo-β-lactamases (MBLs) are a diverse group of zinc-dependent enzymes produced by bacteria to neutralize beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. Unlike serine-beta-lactamases (Classes A, C, and D), MBLs utilize one or two divalent zinc ions in their active site to facilitate the nucleophilic attack and subsequent hydrolysis of the beta-lactam ring. These enzymes are primarily found in Gram-negative pathogens such as Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, where they contribute to high-level multidrug resistance. MBLs are particularly clinically significant because they are not inhibited by traditional beta-lactamase inhibitors like clavulanic acid or avibactam, leaving very few therapeutic options for infected patients. Current drug development efforts focus on novel boronates and chelator-based inhibitors that can restore the efficacy of carbapenems and other last-resort antibiotics. The rapid global dissemination of MBL-encoding genes, such as NDM-1, via mobile genetic elements represents a major threat to modern medicine and public health.

Other names

Metallo-beta-lactamaseClass B beta-lactamaseZinc-dependent beta-lactamaseCarbapenem-hydrolyzing metallo-beta-lactamaseNDM (New Delhi metallo-beta-lactamase)VIM (Verona integron-encoded metallo-beta-lactamase)IMP (Imipenemase)

Inhibition of the enzyme's catalytic activity by chelating essential zinc ions or binding to the active site to prevent the hydrolysis of the beta-lactam ring in antibiotics.