Bacterial metallo-β-lactamase (MBL) (MBL)

Bacterial metallo-β-lactamases (MBLs) are a class of zinc-dependent enzymes that confer broad-spectrum resistance to nearly all β-lactam antibiotics, including carbapenems, which are often considered drugs of last resort (MDPI, 2024; NIH, 2020). Unlike serine-β-lactamases, MBLs utilize one or two zinc ions in their active site to facilitate the nucleophilic attack and hydrolysis of the β-lactam ring (MDPI, 2024; NIH, 2014). These enzymes are primarily found in Gram-negative pathogens such as Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, and their genes (e.g., blaNDM, blaVIM, blaIMP) are frequently carried on mobile genetic elements, facilitating rapid global dissemination (NIH, 2020; MSD Manuals). Because MBLs are not inhibited by traditional β-lactamase inhibitors like clavulanic acid or tazobactam, they represent a significant therapeutic challenge (MDPI, 2024; NIH, 2021). Current drug development efforts focus on novel inhibitors like taniborbactam and xeruborbactam, which aim to restore the efficacy of co-administered antibiotics against multidrug-resistant infections (Healio, 2023; NIH, 2021).

Other names

Class B beta-lactamaseZn-dependent beta-lactamaseMetallo-beta-lactamaseAmbler Class B beta-lactamaseZinc-dependent carbapenemase

Inhibition of the enzyme's catalytic activity by binding to the active site or chelating the essential zinc ions (Zn2+), preventing the hydrolysis of the beta-lactam ring and restoring the activity of co-administered beta-lactam antibiotics (MDPI, 2024; NIH, 2021).