The sequence-activity relationship between metallo-β-lactamases IMP-1, IMP-6, and IMP-25 suggests an evolutionary adaptation to meropenem exposure

Abstract

Metallo-β-lactamases are important determinants of antibacterial resistance. In this study, we investigate the sequence-activity relationship between the closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more efficient enzyme across the overall spectrum of tested β-lactam antibacterial agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation distinguishing IMP-25 from IMP-1 and IMP-6 may affect enzyme activity via Asn233. Copyright © 2012, American Society for Microbiology. All Rights Reserved.