NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli

A clinical Escherichia coli isolate resistant to all beta-lactams, including carbapenems, expressed a novel metallo-beta-lactamase (MBL), NDM-4, differing from NDM-1 by a single amino acid substitution (Met154Leu). NDM-4 possessed increased hydrolytic activity toward carbapenems and several cephalosporins compared to that of NDM-1. This amino acid substitution was not located in the known active sites of NDM-1, indicating that remote amino acid substitutions might also play a role in the extended activity of this MBL.