Class B metallo-beta-lactamase (MBL)

Class B metallo-beta-lactamases (MBLs) are a group of zinc-dependent enzymes produced by bacteria that confer resistance to a broad range of beta-lactam antibiotics, including carbapenems, penicillins, and cephalosporins, but notably not monobactams like aztreonam [1, 5, 12]. Unlike Class A, C, and D beta-lactamases which use a serine-based mechanism, MBLs utilize one or two zinc ions in their active site to facilitate the nucleophilic attack and hydrolysis of the beta-lactam ring [1, 5, 8]. Key members of this class include New Delhi metallo-beta-lactamase 1 (NDM-1) and Verona integron-encoded metallo-beta-lactamases (VIM-1, VIM-2), which have spread globally among Gram-negative pathogens like Klebsiella pneumoniae and Pseudomonas aeruginosa [7, 11, 16]. Because they are not inhibited by traditional beta-lactamase inhibitors like clavulanic acid or avibactam, they represent a significant challenge in clinical settings [1, 9, 16]. Current therapeutic strategies focus on developing novel MBL inhibitors, such as boronate-based compounds (e.g., taniborbactam), to be used in combination with existing antibiotics to restore their efficacy against multi-drug resistant infections [6, 10, 12].

Other names

Class B metallo-β-lactamases – predominantly NDM-1, VIM-1, VIM-2Metallo-beta-lactamaseClass B beta-lactamaseNDM-1VIM-1VIM-2New Delhi metallo-beta-lactamase 1Verona integron-encoded metallo-beta-lactamase 1Verona integron-encoded metallo-beta-lactamase 2IMP-type metallo-beta-lactamase

Inhibition of the enzyme's catalytic activity by chelating active-site zinc ions or mimicking the tetrahedral transition state of beta-lactam hydrolysis [1, 3, 12].