Genetic and enzymatic characterization of two novel bla(NDM-36, -37) variants in Escherichia coli strains

The widespread of different NDM variants in clinical Enterobacterales isolates poses a serious public health concern, which requires continuous monitoring. In this study, three E. coli strains carrying two novel bla(NDM) variants of bla(NDM-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 the bla(NDM-36, -37) enzymes and their carrying strains. The bla(NDM-36, -37) harboring E. 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 of bla(NDM-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 novel bla(NDM) variants in E. coli isolated from the same patient. The work provides insights into the enzymatic function and demonstrates the ongoing evolution of NDM enzymes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10096-023-04576-y.