EBioMedicine · 2025
Global emergence of Carbapenem-resistant Hypervirulent Klebsiella pneumoniae driven by an IncFIIK34 KPC-2 plasmid.
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Jiang Jianping, Wang Leilei, Hu Yiyi, Chen Xin, Li Pei, Zhang Jianfeng, Zhang Yixin, Su Jiachun, Xu Xiaogang, Xiao Yonghong, Liu Zhengyin, Yu Yunsong, Gao Hainv, Doi Yohei, van Duin David, Fowler Vance G, Chen Liang, Wang Minggui
Аннотация
BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been increasingly reported worldwide, posing a severe challenge to public health; however, the mechanisms driving its emergence and global dissemination remain unclear.
METHODS: We analysed CR-hvKp strains derived from canonical hvKp backgrounds, and acquired a carbapenemase-encoding gene. These strains were identified from 485 CRKp isolates in the CRACKLE-2 China cohort, 259 CRKp isolates from a multi-centre study, and 67,631 K. pneumoniae genomes available in GenBank. Clinical isolates harbouring the IncFIIK34 KPC-2 plasmid were selected for genome sequencing, RNA-Seq, conjugation assays, in vivo, ex vivo, and in vitro phenotypic characterisation.
FINDINGS: Analysis of clinical CR-hvKp isolates and the 414 genomes from 24 countries available in GenBank identified an IncFIIK34 KPC-2 plasmid as the prevalent KPC plasmid (detected in 25%, 45/178 of KPC-producing CR-hvKp). Compared with the epidemic IncFIIK2 KPC-2 plasmid, the IncFIIK34 KPC-2 plasmid exhibited a 100- to 1000-fold increase in conjugation frequency (10-4-10-5 vs. 10-7) and an in vitro growth advantage under meropenem challenge-likely due to the overexpression of conjugation-related genes and an increased blaKPC copy number and expression. CR-hvKp isolates and hvKp transconjugants carrying this plasmid often exhibited reduced mucoviscosity, while retaining hypervirulence in both murine models and human neutrophil assays.
INTERPRETATION: The IncFIIK34 plasmid may be a key factor driving the global dissemination of CR-hvKp, underscoring the urgent need for enhanced molecular surveillance of this emerging pathogen.
FUNDING: National Natural Science Foundation of China and National Institutes of Health.
METHODS: We analysed CR-hvKp strains derived from canonical hvKp backgrounds, and acquired a carbapenemase-encoding gene. These strains were identified from 485 CRKp isolates in the CRACKLE-2 China cohort, 259 CRKp isolates from a multi-centre study, and 67,631 K. pneumoniae genomes available in GenBank. Clinical isolates harbouring the IncFIIK34 KPC-2 plasmid were selected for genome sequencing, RNA-Seq, conjugation assays, in vivo, ex vivo, and in vitro phenotypic characterisation.
FINDINGS: Analysis of clinical CR-hvKp isolates and the 414 genomes from 24 countries available in GenBank identified an IncFIIK34 KPC-2 plasmid as the prevalent KPC plasmid (detected in 25%, 45/178 of KPC-producing CR-hvKp). Compared with the epidemic IncFIIK2 KPC-2 plasmid, the IncFIIK34 KPC-2 plasmid exhibited a 100- to 1000-fold increase in conjugation frequency (10-4-10-5 vs. 10-7) and an in vitro growth advantage under meropenem challenge-likely due to the overexpression of conjugation-related genes and an increased blaKPC copy number and expression. CR-hvKp isolates and hvKp transconjugants carrying this plasmid often exhibited reduced mucoviscosity, while retaining hypervirulence in both murine models and human neutrophil assays.
INTERPRETATION: The IncFIIK34 plasmid may be a key factor driving the global dissemination of CR-hvKp, underscoring the urgent need for enhanced molecular surveillance of this emerging pathogen.
FUNDING: National Natural Science Foundation of China and National Institutes of Health.