Class B1 metallo-beta-lactamase (B1 MBL)

Class B1 metallo-β-lactamases (MBLs) are a clinically significant group of bacterial enzymes that provide broad-spectrum resistance to nearly all β-lactam antibiotics, including carbapenems, which are often the last line of defense against multi-drug resistant infections [1, 2]. Unlike serine-β-lactamases, which use a covalent serine-nucleophile mechanism, MBLs utilize one or two zinc ions in their active site to activate a water molecule for the nucleophilic attack and subsequent hydrolysis of the β-lactam ring [4, 10]. The B1 subclass is the most prevalent and diverse, featuring notorious variants such as New Delhi metallo-β-lactamase (NDM), Verona integron-encoded metallo-β-lactamase (VIM), and imipenemase (IMP) [2, 8]. These enzymes are typically encoded on mobile genetic elements, facilitating their rapid global spread among Gram-negative pathogens like Klebsiella pneumoniae and Pseudomonas aeruginosa [6, 12]. Currently, there are no FDA-approved inhibitors specifically targeting MBLs, although several candidates like taniborbactam and xeruborbactam are in clinical development [13, 14]. The development of effective inhibitors is complicated by the structural diversity of MBL active sites and the potential for off-target effects on essential human metalloenzymes [3, 11].

Other names

Ambler class B1 beta-lactamaseZinc-dependent beta-lactamase subclass B1NDM-type metallo-beta-lactamaseVIM-type metallo-beta-lactamaseIMP-type metallo-beta-lactamaseMetallo-beta-lactamase subclass B1

Inhibition of the enzyme's catalytic activity by coordinating with the active-site zinc ions or mimicking the transition state, thereby preventing the hydrolysis of beta-lactam antibiotics and restoring their efficacy.