Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery

Resistance to beta-lactam antibiotics is rapidly growing, substantially due to the spread of serine-beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), which efficiently catalyse beta-lactam hydrolysis. Combinations of a beta-lactam antibiotic with an SBL inhibitor have been clinically successful; however, no MBL inhibitors have been developed for clinical use. MBLs are a worrying resistance vector because they catalyse hydrolysis of all beta-lactam antibiotic classes, except the monobactams, and they are being disseminated across many bacterial species worldwide. Here we review the classification, structures, substrate profiles, and inhibition mechanisms of MBLs, highlighting current clinical problems due to MBL-mediated resistance and progress in understanding and combating MBLmediated resistance.

Automated summary

Resistance to beta-lactam antibiotics is a growing concern due to the spread of serine-beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), which efficiently break down beta-lactam antibiotics. While inhibitors for SBLs have been successful in clinical use, there are currently no inhibitors for MBLs. MBLs are particularly worrisome as they can break down most beta-lactam antibiotics and are rapidly disseminating across bacterial species worldwide.