Subclass B3 metallo-beta-lactamase (B3 MBL)

Subclass B3 metallo-beta-lactamases (MBLs) are a distinct group of zinc-dependent enzymes that confer broad-spectrum resistance to beta-lactam antibiotics, including carbapenems, which are often considered last-resort treatments (NIH, 2020; Frontiers, 2023). Unlike the more common B1 subclass (e.g., NDM, VIM), B3 MBLs are phylogenetically diverse and often originate from environmental or opportunistic bacteria like Stenotrophomonas maltophilia (L1) and Elizabethkingia meningoseptica (GOB-1) (NIH, 2020; ASM, 2016). They typically utilize two zinc ions in their active site to facilitate the nucleophilic attack and hydrolysis of the beta-lactam ring, though they are notably inactive against monobactams like aztreonam (NIH, 2020; Wikipedia, 2024). These enzymes represent a significant clinical challenge because they are not inhibited by traditional beta-lactamase inhibitors like clavulanic acid or tazobactam, and no MBL-specific inhibitors are currently approved for clinical use (NIH, 2020; MSD Manuals, 2024). Research is focused on developing novel inhibitors, such as zinc chelators and boronic acid derivatives, to restore the efficacy of carbapenems (NIH, 2020; Frontiers, 2023). However, the structural diversity within the B3 subclass and potential off-target effects on human metallo-enzymes remain major hurdles in drug development (Frontiers, 2023).

Other names

Class B3 metallo-beta-lactamaseSubgroup B3 metallo-beta-lactamaseB3-type MBLZinc-dependent beta-lactamase subclass B3

Subclass B3 metallo-beta-lactamases are targeted by inhibitors that typically act through zinc chelation, which removes the essential metal ions required for catalysis, or through competitive binding to the active site to prevent the hydrolysis of beta-lactam antibiotics (NIH, 2020; Frontiers, 2023).