Bacterial metallo-beta-lactamase (MBL) (MBL)

Bacterial metallo-beta-lactamases (MBLs) are a diverse group of zinc-dependent enzymes that confer broad-spectrum resistance to beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [1, 2]. Unlike serine-beta-lactamases, MBLs utilize one or two zinc ions in their active site to facilitate the nucleophilic attack and hydrolysis of the beta-lactam ring, rendering the antibiotic inactive [3, 6]. These enzymes are primarily produced by Gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and members of the Enterobacteriaceae family [2, 13]. The rapid global dissemination of MBL genes, such as NDM-1, VIM, and IMP, via mobile genetic elements has created a significant public health threat [10, 15]. These enzymes are particularly problematic because they are not inhibited by traditional beta-lactamase inhibitors like clavulanic acid, tazobactam, or avibactam [4, 6]. Therapeutic strategies focus on developing novel MBL inhibitors, such as taniborbactam and xeruborbactam, which are designed to restore the efficacy of co-administered antibiotics [11, 12]. These inhibitors often work by binding to the active site or chelating the essential zinc cofactors [4, 14]. Clinical management of MBL-producing infections remains a major challenge due to the limited number of effective treatment options and the potential for off-target effects on human metalloenzymes [3, 11].

Other names

Class B beta-lactamase [5]Zn-dependent beta-lactamase [1]Metallo-beta-lactamase [1]BBL [5]Carbapenemase (Class B) [7]

Inhibition of the enzyme's catalytic activity by binding to the active site or chelating essential zinc ions to prevent antibiotic hydrolysis [4, 14].