High prevalence of KPC-3 in carbapenem-resistant Pseudomonas aeruginosa across multiple clonal lineages in China
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Background
The epidemiology of Klebsiella pneumoniae carbapenemase (KPC)-producing Pseudomonas aeruginosa is rapidly evolving in China. While bla KPC-2 remains the predominant KPC variant in P. aeruginosa , bla KPC-3 has rarely been documented in this pathogen. This study investigated the molecular epidemiology, resistance and virulence characteristics, and plasmid features of bla KPC-3 -producing CRPA isolates collected from a tertiary hospital in eastern China.
Methods
A total of 65 non-duplicate CRPA isolates collected in 2023 were subjected to whole-genome sequencing. Antimicrobial susceptibility testing, phylogenetic analysis, plasmid characterization, conjugation experiments, and virulence assays were performed.
Results
Among the 65 CRPA isolates, 37 (56.9%) carried bla KPC-3 . These bla KPC-3 -positive isolates belonged to four sequence types (STs), including ST1076 (62.2%), ST463 (21.6%), ST646 (10.8%), and ST3393 (5.4%). To our knowledge, this is the first report of bla KPC-3 in P. aeruginosa ST463, ST646 and ST3393. All isolates exhibited extensive drug resistance, and 51.8% were resistant to ceftazidime-avibactam.
Phylogenetic analysis indicated that bla KPC-3 dissemination was driven by both clonal expansion and horizontal transmission. Comparative genomic analysis identified three kinds of bla KPC-3 -carrying plasmid. A transferable IncP-2 megaplasmid was widely distributed among ST1076, ST646, and ST3393 isolates, whereas non-transferable IncP-10 plasmids were primarily restricted to ST463. The genetic environments and plasmid backbones of bla KPC-3 were highly conserved and closely related to those of bla KPC-2 and its variants, suggesting evolution from pre-existing bla KPC-2 -associated plasmids. Virulence analysis demonstrated marked heterogeneity across lineages.
ST463 isolates co-harbored exoU and exoS , exhibited enhanced biofilm formation and pyocyanin production, and caused significantly higher mortality in the G. mellonella infection model, indicating a hypervirulent phenotype.
Conclusions
The bla KPC-3 is becoming an increasingly important determinant of carbapenem resistance in P. aeruginosa in China. The IncP-2 megaplasmid and IncP-10 plasmid derived bla KPC-3 spread across multiple lineages. Continuous genomic surveillance and enhanced infection control measures are urgently needed to prevent its further prevalence in clinical settings.
