Imipenemase metallo-beta-lactamase (IMP)

Imipenemase (IMP) metallo-beta-lactamases are a group of clinically significant enzymes that confer broad-spectrum resistance to nearly all beta-lactam antibiotics, including carbapenems, which are often considered drugs of last resort (UniProt: P52663). These enzymes belong to Ambler Class B and require zinc ions for their catalytic mechanism, allowing them to hydrolyze the beta-lactam ring of penicillins, cephalosporins, and carbapenems, though they are typically inhibited by monobactams like aztreonam (PubMed: 28848236). IMP variants are primarily found in Gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae, often carried on mobile genetic elements like integrons and plasmids, facilitating rapid spread (NCBI: PMC6521595). Because they are not inhibited by traditional beta-lactamase inhibitors like clavulanic acid or tazobactam, they represent a major therapeutic challenge in treating healthcare-associated infections. Current drug development focuses on novel non-beta-lactam inhibitors, such as boronate derivatives like taniborbactam, that can effectively bind the binuclear zinc active site to restore antibiotic potency (PubMed: 31511345).

Other names

IMP-type carbapenemaseMetallo-beta-lactamase IMPClass B1 beta-lactamaseZinc-dependent carbapenemase

Inhibition of the enzyme's catalytic activity by chelating active-site zinc ions or through competitive binding, thereby preventing the hydrolysis of beta-lactam antibiotics and restoring their efficacy.