Metallo-beta-lactamase (MBL) (MBL)

Metallo-beta-lactamases (MBLs) are a diverse group of zinc-dependent enzymes (Ambler Class B) that catalyze the hydrolysis of nearly all beta-lactam antibiotics, including carbapenems, penicillins, and cephalosporins [1][3]. These enzymes, notably the IMP-1 and NDM-1 variants, are primarily found in Gram-negative bacteria such as Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, where they serve as a major mechanism of multidrug resistance [2][4]. Unlike serine-beta-lactamases, MBLs utilize one or two zinc ions in their active site to activate a water molecule for nucleophilic attack on the beta-lactam ring [3]. This unique mechanism makes them resistant to traditional inhibitors like clavulanic acid, tazobactam, and avibactam [1]. Consequently, MBL-producing pathogens are associated with high mortality rates in clinical settings due to limited treatment options [4]. Therapeutic development focuses on novel cyclic boronate inhibitors like taniborbactam and xeruborbactam, which can inhibit both serine- and metallo-beta-lactamases, or the use of monobactams like aztreonam which are intrinsically stable against MBL-mediated hydrolysis [4][5].

Other names

Class B beta-lactamaseZinc-dependent beta-lactamaseIMP-type metallo-beta-lactamaseNDM-type metallo-beta-lactamaseNew Delhi metallo-beta-lactamase 1Imipenemase 1VIM-type metallo-beta-lactamase

Inhibition of the metallo-beta-lactamase enzyme by binding to the active site or chelating the essential zinc ions, thereby preventing the hydrolysis of beta-lactam antibiotics [3][4].