Metallo-β-lactamase enzyme (MBL)

Metallo-β-lactamase enzymes (MBLs) are a diverse group of zinc-dependent hydrolase enzymes found predominantly in Gram-negative bacteria that catalyze the hydrolysis of a wide variety of β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, except monobactams[1][2][5][6]. These enzymes require one or two zinc ions in their active sites to activate a water molecule, enabling nucleophilic attack on the β-lactam ring, which leads to antibiotic inactivation[1][2][3][4][5]. MBLs are divided into subclasses B1, B2, and B3 based on sequence and structure, all featuring variations of a key αβ/βα fold and metal coordination motifs[1][3]. They are a major cause of resistance to β-lactam antibiotics in clinically relevant bacteria such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia[1][2][3]. MBLs are considered high-priority antimicrobial resistance targets since current β-lactamase inhibitors such as clavulanic acid and avibactam do not block these enzymes, and there are no approved MBL inhibitors as of 2024, though several are in clinical trials[2][5]. The genes encoding MBLs (such as NDM, VIM, IMP) spread rapidly via horizontal gene transfer, contributing to pandemic multidrug resistance crises and limiting treatment options for life-threatening infections[1][2][5]. Detection of MBLs in clinical isolates signals a high risk of treatment failure, and monitoring for their gene presence is a key biomarker for resistance surveillance and patient management.

Other names

Metallo-beta-lactamaseMBLMetallo-β-lactamaseβ-lactamase (metallo-dependent subclass)B1/B2/B3 β-lactamasesNDM-1VIMIMPL1AIM-1BlaBGOB

Hydrolysis of the β-lactam ring in antibiotics, inactivation of β-lactam antibiotics, Inhibition of the metallo-β-lactamase zinc active site (for inhibitor drugs)