Molecular epidemiology and genomic insights into the transmission of carbapenem-resistant NDM-producing Escherichia coli

Escherichia coli is a leading cause of nosocomial infections. Carbapenem-resistant E. coli (CREC), which has been frequently isolated in recent years because of the widespread use of carbapenems, poses a significant challenge to clinical anti-infection treatment. In this study, a total of 27 CREC strains were identified from a set of 795 E. coli isolates collected over a two-year period from a tertiary hospital in China. Whole-genome sequencing revealed that 17 strains carried the bla(NDM-5) gene, 5 strains carried the bla(NDM-1) gene, 1 strain carried the bla(NDM-7) gene, and the remaining 4 strains carried the bla(KPC-2) gene. All 23 NDM-producing E. coli strains were resistant to all antibiotics except tigecycline, colistin, and cefiderocol. Nine different sequence types (STs) were identified, with ST410 and ST167 being the most prevalent. All of the bla(NDM) genes were located on conjugatable plasmids. We identified five different plasmid replicon types ranging in size from 20 kb to 200 kb, with the IncX3-type plasmid, 46 kb in size, being a key factor in facilitating the horizontal transmission of the bla(NDM) gene in E. coli. The structure surrounding the bla(NDM) gene was relatively conserved and mainly contained the following structures: IS3000-ISAbal25-IS5-bla(NDM)-ble(MBL)-trpF-dsbC-IS26. However, the plasmid backbone structure was highly variable, which indicates that the bla(NDM) gene has already spread horizontally among different types of plasmids. In addition, we discovered two copies of the bla(NDM-5) gene in a single plasmid (pEC29-NDM-5), with an identical structure around the gene and the complete sequence of the class 1 integron. Our findings detail the prevalence of CREC in a tertiary hospital in China, and the emergence of multiple copies of the bla(NDM-5) gene on a single plasmid needs our attention.