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

Metallo-beta-lactamases (MBLs), classified as Ambler Class B, are bacterial enzymes that utilize one or two zinc ions in their active site to catalyze the hydrolysis of nearly all beta-lactam antibiotics, including carbapenems. Unlike Class A, C, and D beta-lactamases which use a serine-based mechanism, MBLs employ a metal-dependent water molecule to break the beta-lactam ring, making them resistant to traditional inhibitors like clavulanic acid or avibactam. These enzymes are primarily found in Gram-negative pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, where they contribute significantly to multi-drug resistance. The rapid global spread of MBL genes, particularly NDM-1, poses a severe threat to public health by rendering "last-resort" carbapenems ineffective. Therapeutic strategies currently focus on developing novel boronate-based inhibitors or combining MBL-stable antibiotics like aztreonam with other inhibitors to overcome this resistance. (Sources: StatPearls: Beta Lactamase, PubMed: PMC7449195, UniProt: P0AD64).

Other names

Class B beta-lactamaseZinc-dependent beta-lactamaseMetallo-beta-lactamaseCarbapenemase Class B

Inhibition of the zinc-dependent active site to prevent the hydrolysis of beta-lactam antibiotics, thereby restoring the efficacy of co-administered antibacterial agents.