Emergence of a novel sequence type carbapenem-resistant hypervirulent Klebsiella pneumoniae ST6417 harboring blaNDM-5 on the lncX3 plasmid

Abstract

ABSTRACT Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is a significant pathogen causing major public health problems worldwide. This study characterized a novel sequence type 6417 (ST6471) CR-hvKP strain recovered from the blood of a male patient with septicemia. Strain CR2021 is not susceptible to carbapenems, cephalosporin, sulfonamides, quinolones, or levofloxacin and is susceptible to amikacin and tigecycline. Molecular typing indicated that ST6417 is derived from the most dominant hypervirulent K. pneumoniae (hvKP) clone in China, ST23, with a single-locus variation in tonB. The genomic characterization of CR2021, which contains three plasmids, was performed through whole-genome sequencing. The plasmid pCR2021_IncFII contains 12 antibiotic resistance genes [blaCTX-M-3, blaTEM-1B, blaDHA-1, aac (3)-Ild, aadA16, sul1, sul2, qnrB4, ARR-3, dfrA27, qacE, merACDE], all of which are associated with genetic elements. The plasmid pCR2021_IncFIB carries crucial virulence-related genes, while the plasmid pCR2021_IncX3 only harbors the blaNDM-5 resistance gene and exhibits 99% similarity with two other blaNDM-5-carrying IncX3 plasmids (pSHX180-NDM5, pNDM-K725), with coverage of 87% and 100%, respectively. The blaNDM-5 genetic region contains an additional IS26-Tn3 genetic module. Serum killing and anti-human neutrophil phagocytosis tests indicated that CR2021 exhibits high virulence, which was further confirmed in a Galleria mellonella larvae infection model. CR-hvKP is becoming more prevalent in China; however, the majority have evolved from the multidrug resistance clone ST11 and its variants by acquiring virulence factors. Conversely, CR-hvKP derived from hvKP, such as the clone ST23, remains relatively rare. Therefore, the discovery of ST6417 underscores the need for further research into the genetic characteristics and evolution of bacteria.IMPORTANCEST11 and its variants, which often exhibit drug resistance, represent popular clones of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) in China, often leading to high morbidity and mortality rates owing to their high virulence and robust drug resistance. Conversely, CR-hvKP, originating from the high-virulence sequence type ST23, remains rarely reported. In this study, we identified a novel ST6417 CR-hvKP strain derived from ST23, carrying blaNDM-5 on an IncX3 plasmid conferring resistance to carbapenems. In addition, we elucidate its virulence, resistance to drugs, and genetic characteristics. The discovery of ST6417 highlights the diverse pathways in the evolution of CR-hvKP, warranting increased attention.

Keywords

• Klebsiella pneumoniae
• ST6417
• carbapenem resistance gene
• hypervirulent
• IncX3