Verona integron-encoded metallo-beta-lactamase 1 (VIM-1) (VIM-1)

Verona integron-encoded metallo-beta-lactamase 1 (VIM-1) is a zinc-dependent enzyme that confers broad-spectrum resistance to beta-lactam antibiotics, including carbapenems, which are often used as last-resort treatments for serious infections [1, 2]. First identified in Pseudomonas aeruginosa, VIM-1 has since spread globally across various Gram-negative species, including Klebsiella pneumoniae and Escherichia coli, primarily through mobile genetic elements like class 1 integrons [2, 3]. The enzyme operates by utilizing one or two zinc ions in its active site to facilitate the nucleophilic attack of a water molecule on the beta-lactam ring, thereby inactivating the antibiotic [1, 4]. This mechanism is distinct from serine-beta-lactamases and renders VIM-1-producing bacteria resistant to most clinically available beta-lactamase inhibitors such as clavulanic acid, tazobactam, and avibactam [4, 5]. Consequently, VIM-1 is a high-priority target for the development of next-generation inhibitors, such as bicyclic boronates like taniborbactam and xeruborbactam, which are designed to bind the metallo-enzyme active site and restore the efficacy of carbapenems and cephalosporins [5, 6]. The presence of VIM-1 in clinical isolates is a significant biomarker for multi-drug resistance and necessitates specialized diagnostic testing to guide appropriate antibiotic therapy [3, 7].

Other names

VIM-1Verona integron-encoded metallo-beta-lactamase 1blaVIM-1Metallo-beta-lactamase VIM-1

Inhibitors like taniborbactam act as transition-state analogs that bind to the zinc ions in the active site of VIM-1, preventing the enzyme from hydrolyzing the beta-lactam ring of co-administered antibiotics [4, 5].