Imipenemase metallo-beta-lactamase (IMP) (IMP)

IMP-type metallo-beta-lactamases (IMPs) are a critical family of Ambler Class B1 enzymes that mediate high-level resistance to a wide array of beta-lactam antibiotics, including carbapenems, cephalosporins, and penicillins (PMID: 15845483). These enzymes are characterized by their requirement for divalent zinc ions to catalyze the hydrolysis of the beta-lactam ring, a mechanism distinct from the covalent acyl-enzyme intermediate used by serine-beta-lactamases (PMID: 24513114). Originally discovered in Pseudomonas aeruginosa in Japan, IMP variants have disseminated globally via mobile genetic elements like integrons and plasmids, frequently appearing in Enterobacterales and Acinetobacter species (PMID: 20660673). The presence of IMP-type enzymes in clinical isolates significantly limits therapeutic options, as they are not inhibited by commercially available inhibitors such as clavulanic acid, sulbactam, or tazobactam (PMID: 31601601). Consequently, infections caused by IMP-producing bacteria are associated with high mortality rates and represent a major public health threat. Ongoing drug discovery efforts are focused on identifying potent MBL inhibitors, such as cyclic boronates like taniborbactam and xeruborbactam, to be used in combination with existing beta-lactams to overcome this resistance mechanism (PMID: 33536237).

Other names

IMP-1ImipenemaseClass B1 metallo-beta-lactamaseIMP-type MBL

The enzyme utilizes one or two zinc ions to activate a water molecule, which then performs a nucleophilic attack on the beta-lactam ring's carbonyl group, leading to ring opening and antibiotic inactivation (PMID: 24513114).