Metallo-β-lactamase (MBL)

Metallo-β-lactamases (MBLs) are a class of enzymes (specifically, class B β-lactamases) that confer resistance to a broad spectrum of β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. They achieve this by catalyzing the hydrolysis of the β-lactam ring—a core structural feature essential for antibiotic activity—rendering these drugs ineffective. MBLs require one or two zinc ions in their active site for catalytic activity. The zinc ions activate a water molecule that attacks the carbonyl group in the β-lactam ring, leading to its hydrolysis. These enzymes are not inhibited by traditional mechanism-based inhibitors such as clavulanate or tazobactam. Genes encoding MBLs have spread widely among Gram-negative bacteria via mobile genetic elements such as plasmids. This dissemination has made them major contributors to multidrug resistance worldwide—especially concerning because they can degrade carbapenems ("last-resort" antibiotics). Currently there are no clinically approved inhibitors specifically targeting metallo-β-lactamases. Their evolutionary flexibility allows rapid adaptation under antibiotic pressure.

Other names

Metallo-beta-lactamaseMBLsClass B β-lactamase

Hydrolyzes the β-lactam ring of β-lactam antibiotics, rendering them ineffective.