Verona integron-encoded metallo-β-lactamase 2 (VIM-2)

Verona integron-encoded metallo-β-lactamase 2 (VIM-2) is a potent enzyme produced by various Gram-negative bacteria, most notably Pseudomonas aeruginosa, which confers broad-spectrum resistance to nearly all beta-lactam antibiotics, including carbapenems [1, 2]. As a Class B metallo-beta-lactamase, VIM-2 utilizes two zinc ions in its active site to facilitate the nucleophilic attack and subsequent hydrolysis of the beta-lactam ring, rendering the antibiotic inactive [3]. This enzyme is typically encoded on mobile genetic elements like integrons and plasmids, allowing for rapid horizontal gene transfer between bacterial species and contributing significantly to the global crisis of antimicrobial resistance [2]. In clinical settings, VIM-2-producing pathogens are associated with high morbidity and mortality due to the lack of effective treatment options, as traditional beta-lactamase inhibitors like clavulanic acid and tazobactam are ineffective against MBLs [4]. Current therapeutic strategies focus on the development of novel broad-spectrum inhibitors, such as taniborbactam (VNRX-5133), which are designed to bind the MBL active site and restore the efficacy of co-administered antibiotics [5]. Understanding the structural biology and mechanism of VIM-2 is essential for the design of next-generation inhibitors that can overcome the challenges posed by metallo-beta-lactamase-mediated resistance [3, 5]. Citations: [1] UniProt P0C0S1; [2] Poirel L, et al. (2000) Antimicrob Agents Chemother; [3] Bonomo RA, et al. (2018) Cold Spring Harb Perspect Med; [4] Docquier JD, et al. (2010) Drug Resist Updat; [5] Liu J, et al. (2020) Reviews in Medicinal Chemistry.

Other names

VIM-2Metallo-beta-lactamase VIM-2blaVIM-2Carbapenem-hydrolyzing metallo-beta-lactamase VIM-2

Inhibition of the metallo-beta-lactamase enzyme activity, typically through the use of cyclic boronates or other chelating moieties that interact with the active-site zinc ions to prevent the hydrolysis of beta-lactam antibiotics.