Dissemination of bla NDM -harboring plasmids in carbapenem-resistant and hypervirulent Klebsiella pneumoniae

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global public health threat, and CRKP strains carrying bla NDM plasmids are of particular concern. Here, the antimicrobial resistance and molecular epidemiological characteristics of 59 CRKP strains isolated from patients receiving care at a tertiary hospital in China from 2019 to 2021 were determined through antimicrobial resistance testing and genomic sequence analysis. We analyzed the genetic characteristics and transmissibility of bla NDM -harboring plasmids through S1-digested pulsed field gel electrophoresis, Southern blotting, and conjugation assays. The virulence levels of the strains were evaluated using a Galleria mellonella larvae infection model. All the CRKP strains were multidrug resistant, but none were resistant to colistin or tigecycline. A total of eight sequence types (STs) were detected in these CRKPs, with ST11 (39/59) and ST15 (12/59) being the most common. Among the carbapenemase genes, bla KPC (39/59) and bla NDM (18/59) were the most common, with bla KPC-2 transmitted mainly through ST11 clones and bla NDM-5 transmitted through ST15 clones. The bla NDM -harboring plasmids primarily belong to the incompatibility type IncX3 (14/18). IS 26 -mediated gene recombination, sequence insertion, and plasmid integration were observed to occur during the dissemination process. The resistance gene profile mediated by bla NDM -harboring plasmids can be transferred through conjugation, which have almost no fitness cost and is extremely stable after passage. Six of these strains presented carbapenem resistance combined with hypervirulence (CR-hvKP), including ST23-KL1, ST218-KL57, ST17-KL112, and ST147-KL64. Additionally, bla NDM -harboring plasmids can disseminate rapidly over large surface areas and persist for a long time in medical institutions, leading to outbreaks of highly resistant clones associated with CR-hvKP. IMPORTANCE The appearance of plasmids carrying bla NDM and the rise of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have significantly escalated the public health risk associated with Carbapenem-resistant Klebsiella pneumoniae (CRKP). In this study, we described the resistance rates, virulence factors, and molecular epidemiology of 59 CRKP isolated from patients at a tertiary hospital in China from 2019 to 2021. Beyond this, we also assessed the characteristics of bla NDM -harboring plasmids and their dissemination patterns among CRKP, especially some CR-hvKP. Our research contributes to the field of bla NDM dissemination studies, prompting researchers to formulate strict measures to prevent and control the development of bla NDM -harboring plasmids, which is instrumental in the clinical development of targeted treatment plans.