Class B metallo-beta-lactamase (MBL) (MBL)

Class B metallo-beta-lactamases (MBLs) are a group of zinc-dependent enzymes produced by bacteria that confer resistance to a broad spectrum of beta-lactam antibiotics, including carbapenems, which are often considered last-resort treatments [1, 3]. Unlike serine beta-lactamases (Classes A, C, and D), MBLs utilize one or two zinc ions in their active site to facilitate the nucleophilic attack of a water molecule on the beta-lactam ring, leading to its hydrolysis [5, 11]. This unique mechanism makes them immune to traditional beta-lactamase inhibitors like clavulanic acid, tazobactam, or avibactam [3, 14]. MBLs are primarily found in Gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales, often carried on mobile genetic elements like plasmids, which facilitates their rapid global spread [4, 12]. The clinical significance of MBLs is profound, as they contribute to multi-drug resistant (MDR) infections with extremely limited therapeutic options [9, 15]. Current drug development focuses on novel inhibitors like taniborbactam and xeruborbactam, or using MBL-stable antibiotics like aztreonam in combination with other inhibitors to overcome co-produced resistance enzymes [7, 10].

Other names

Metallo-beta-lactamaseBBLAmbler class B beta-lactamaseZinc-dependent beta-lactamaseCarbapenemaseNew Delhi metallo-beta-lactamase (NDM)Verona integron-encoded metallo-beta-lactamase (VIM)Imipenemase (IMP)

Inhibition of the enzyme's catalytic activity, typically through zinc chelation or competitive binding at the active site, which prevents the hydrolysis of the beta-lactam ring and restores the efficacy of co-administered antibiotics [3, 8, 11].