metallobetalactamase

Metallobeta-lactamases are zinc-dependent enzymes that hydrolyze beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. They belong to the Ambler class B of beta-lactamases and differ from serine beta-lactamases in their mechanism and inhibition profile.

The active site of metallobeta-lactamases contains zinc ions that activate a water molecule to attack the beta-lactam ring, rendering the antibiotic ineffective. These enzymes have broad substrate spectra and are poorly inhibited by classic beta-lactamase inhibitors such as clavulanic acid, tazobactam, or sulbactam.

Genes encoding metallobeta-lactamases include bla_NDM, bla_VIM, bla_IMP, bla_SPM, bla_SIM, and bla_DIM, among others. These genes are frequently located on plasmids and other mobile elements, enabling rapid spread among Gram-negative bacteria, notably Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, in both clinical and environmental settings.

Clinically, metallobeta-lactamase producers often cause carbapenem-resistant infections and limit therapeutic options. In many cases, aztreonam remains active unless other beta-lactamases co-exist that hydrolyze it. Detection relies on phenotypic tests such as EDTA-based synergy assays, the modified carbapenem inactivation method, and molecular assays for specific bla genes. Prompt recognition supports infection control and targeted therapy.

Treatment of MBL infections is challenging; there is no universally approved MBL-specific inhibitor. Some strategies under investigation include aztreonam in combination with beta-lactamase inhibitors (such as avibactam) to counteract coexisting enzymes, as well as newer agents under development. Infection prevention and antimicrobial stewardship are key to limiting spread.