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

Verona integron-encoded metallo-beta-lactamase 1 (VIM-1) is a critical bacterial enzyme that confers broad-spectrum resistance to nearly all beta-lactam antibiotics, including carbapenems, which are typically reserved for severe, multidrug-resistant infections. First identified in Pseudomonas aeruginosa in Verona, Italy, VIM-1 has since disseminated globally among various Gram-negative pathogens, including Klebsiella pneumoniae and Escherichia coli. As a member of the Ambler Class B (subclass B1) metallo-beta-lactamases, it utilizes two zinc ions in its active site to catalyze the hydrolysis of the beta-lactam ring, thereby inactivating the antibiotic. VIM-1 is particularly challenging in clinical settings because it is not inhibited by conventional beta-lactamase inhibitors such as clavulanic acid, tazobactam, or avibactam. Its presence often leads to multidrug-resistant or even pan-resistant phenotypes, significantly limiting therapeutic options for healthcare-associated infections. Current drug development efforts are focused on novel inhibitors like taniborbactam and xeruborbactam, which aim to restore the efficacy of beta-lactams against VIM-1-producing strains. The enzyme's ability to spread rapidly via mobile genetic elements like integrons and plasmids makes it a major target for antimicrobial stewardship and diagnostic surveillance.

Other names

VIM-1 metallo-beta-lactamaseblaVIM-1Verona integron-borne metallo-beta-lactamase 1Metallo-beta-lactamase VIM-1

Inhibitors of VIM-1 typically function by binding to the active site and either chelating the essential zinc ions or forming stable complexes that prevent the enzyme from hydrolyzing the beta-lactam ring of antibiotics. Substrate antibiotics are inactivated by the enzyme through a zinc-mediated nucleophilic attack by a water molecule on the beta-lactam carbonyl group.