Whole genome sequencing of carbapenem- and polymyxin-resistant clinical isolates of Escherichia coli to analyze resistance mechanisms

Objectives To clarify the resistance phenotypes, genetic and molecular characteristics of carbapenem-polymyxin co-resistant Escherichia coli clinical isolates in China, and provide evidence for clinical infection control. Methods 11 co-resistant E. coli isolates collected from a hospital during 2021–2023 were analyzed retrospectively. Antimicrobial susceptibility testing, modified carbapenem inactivation method (mCIM/eCIM) and whole-genome sequencing (WGS) were performed. Resistance genes, plasmid replicons, multilocus sequence typing (MLST) and phylogenetic analysis based on core genome SNPs were conducted using bioinformatics tools. Results All isolates co-carried bla NDM and mcr-1 genes, with bla NDM-5 (72.7%) as the dominant variant. Heterogeneous plasmid replicon types were detected, and phylogenetic analysis clustered the isolates into three clades. MLST identified seven sequence types (STs), with ST167 (36.4%) being the most prevalent. All isolates were resistant to carbapenems, polymyxins and β-lactams, and universally susceptible to tigecycline. Conclusions The coexistence of bla NDM and mcr-1 is the key cause of carbapenem-polymyxin co-resistance in E. coli . The diverse plasmid replicon types and typical resistance gene profiles highly suggest the potential involvement of plasmid-mediated horizontal gene transfer in resistance gene dissemination, which warrants further experimental verification. The genetic diversity of the isolates indicates no clonal outbreak, but the presence of closely related strains highlights the need for continuous surveillance and strengthened infection control measures to prevent further spread of such multidrug-resistant strains.