Genetic and enzymatic characterization of two novel blaNDM-36, -37 variants in Escherichia coli strains
In this study, threeE. coli strains carrying two novelblaNDM variants ofblaNDM-36, -37 were identified from a patient with refractory urinary tract infection (UTI) in China. We conducted antimicrobial susceptibility testing (AST), enzyme kinetics analysis, conjugation experiment, whole-genome sequencing (WGS), and bioinformatics analysis to characterize theblaNDM-36, -37 enzymes and their carrying strains. TheblaNDM-36, -37 harboringE. coli isolates belonged to ST227, O9:H10 serotype and exhibited intermediate or resistance to all β-lactams tested except aztreonam and aztreonam/avibactam. The genes ofblaNDM-36, -37 were located on a conjugative IncHI2-type plasmid. NDM-37 differed from NDM-5 by a single amino acid substitution (His261Tyr). NDM-36 differed from NDM-37 by an additional missense mutation (Ala233Val). NDM-36 had increased hydrolytic activity toward ampicillin and cefotaxime relative to NDM-37 and NDM-5, while NDM-37 and NDM-36 had lower catalytic activity toward imipenem but higher activity against meropenem in comparison to NDM-5. This is the first report of co-occurrence of two novelblaNDM variants inE. coli isolated from the same patient. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of NDM enzymes.