Genetic and phenotypic characterization of the plasmid-encoded NDM-80 metallo-β-lactamase in Escherichia coli isolated from a pediatric patient

Introduction Carbapenem-resistant Enterobacterales (CRE) strains carrying bla NDM variants pose a significant threat to the health of infected patients worldwide. Methods This study isolated a carbapenem-resistant Escherichia coli ( E. coli ) strain carrying bla NDM– 80 from a patient in an intensive care unit in China. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), plasmid transformation assay, cloning experiment, and steady-state kinetic determinations were performed to investigate antimicrobial susceptibility, the characteristics of the genetic environment, the mechanism of resistance gene transmission, resistance gene function, and antibiotic hydrolysis ability. Results The results indicated that E. coli carrying bla NDM– 80 showed significant resistance to all β-lactam antibiotics except for aztreonam, aztreonam-avibactam, and cefiderocol. WGS analysis revealed that the strain belonged to sequence type (ST) 155 and the O4:H51 serotype. The bla NDM– 80 was carried by an unconjugated plasmid, and its complete genetic structure was found to be IS 5- bla NDM– 80 - ble - trpF - dsbD - IS 26- nmuD - IS Kox3. The bla NDM– 80 had single amino acid substitutions such as V88L, D130N, and M154L compared to bla NDM– 1 , whereas it only had the D130N mutation compared to bla NDM– 5 . The bla NDM– 80 and bla NDM– 5 had similar antimicrobial resistance profiles. However, in the absence of the native promoter, the minimum inhibitory concentrations (MICs) of bla NDM– 80 for imipenem, meropenem, cefepime, and cefiderocol were twice as high as those of bla NDM– 1 . Steady-state kinetic determinations revealed that NDM-80 likely had higher hydrolytic activity against imipenem, meropenem, cefepime, and cefiderocol than NDM-1. Discussion This study is the first to report on the emergence of the bla NDM– 80 variant, shedding light on its functional mechanism. Our findings enrich the repertoire of NDM resistance genes and highlight the need for increased surveillance of pathogens harboring bla NDM variants.