Na Wang, Xiaocui Peng, Huiying Li, Xiaoyu Li, Chunmei Lei, Bu Wang, Jianhua Liu, Wei Zhang
This study identified recurrent candidate chromosome-associated virulence-locus configurations in ST11 hv-CRKP that are distinct from canonical fusion-plasmid architectures. This evidence extends the current models beyond plasmid fusion and underscores the value of genomic surveillance strategies capable of detecting chromosomal virulence, which may be overlooked when surveillance focuses solely on virulence plasmids. Defining this evolutionary trajectory provides a foundation for infection prevention and control, as well as for designing targeted interventions to limit the spread of these high-risk pathogens. Using multiple lines of genomic evidence, we established a framework for assessing candidate chromosomal localizations and identifying breakpoint-associated read signatures.
BACKGROUND: The global rise in hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses a severe threat to public health. However, the evolutionary mechanisms underlying hypervirulence in carbapenem-resistant strains remain incompletely understood. Here, we investigated the genetic basis of hypervirulence in a prevalent carbapenem-resistant lineage.
METHODS: Whole-genome sequencing and comparative genomic analyses were performed on 112 locally collected carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates collected from 2020 to 2022 and 4,636 publicly available K. pneumoniae genomes, including 557 hv-CRKP.
RESULTS: Among 66 hv-CRKP identified locally, the ST11-KL64 lineage was dominant, accounting for 87.9%. As against the classical fusion-plasmid model, these isolates harbored candidate chromosomal virulence-locus configurations, supported by convergent short-read sequencing evidence, with insertion sequences identified at or near the inferred breakpoint regions. IS-positive hv-CRKP isolates included in the phenotypic comparison showed significantly greater virulence in Galleria mellonella infection models than the IS-negative hv-CRKP comparator isolates (log-rank test, p < 0.0001). Global phylogenetic analysis showed that strains carrying related candidate chromosomal virulence-locus configurations clustered within a distinct lineage, with the currently available genomes in this group predominantly originating from China.
CONCLUSION: This study identified recurrent candidate chromosome-associated virulence-locus configurations in ST11 hv-CRKP that are distinct from canonical fusion-plasmid architectures. This evidence extends the current models beyond plasmid fusion and underscores the value of genomic surveillance strategies capable of detecting chromosomal virulence, which may be overlooked when surveillance focuses solely on virulence plasmids. Defining this evolutionary trajectory provides a foundation for infection prevention and control, as well as for designing targeted interventions to limit the spread of these high-risk pathogens. Using multiple lines of genomic evidence, we established a framework for assessing candidate chromosomal localizations and identifying breakpoint-associated read signatures.