Purpose This study retrospectively analyzed the genome characteristics of blaKPC-2 in multidrug-resistant Klebsiella pneumoniae collected from the ICU of a teaching hospital in Shanghai, China.Methods From February 2018 to December 2019, 36 strains of multidrug-resistant Klebsiella pneumoniae were collected from the bronchoalveolar lavage fluid of critically ill patients. The genome of all isolates was obtained through the Illumina sequence, and single nucleotide polymorphisms of the blaKPC-2 gene were analyzed to explore blaKPC-2’s evolutionary characteristics. Different strains’ genetic relationships and homology were studied by constructing an evolutionary tree on a single copy orthologue. Pacbio combined Illumina sequence was conducted to evaluate the structure and potential mobility of drug-resistant plasmids of the strain KP-s26.Results The distribution of resistance and virulence genes had little difference, but most strains had significant differences in the plasmid-encoded region. Most strains (31/36) carried the carbapenemase gene blaKPC-2, with no single nucleotide polymorphism in different strains. Extended-spectrum β-lactamase resistance genes, such as blaCTX-M and blaSHV, were found in the isolates, but no metallo-β-lactamases were detected. All strains with blaKPC-2 coexisted with chromosomal-associated fosfomycin resistance genes fosA6, and the coexistence of blaKPC-2 and blaCTX variants (blaCTX-M-15, blaCTX-M-65, and blaCTX-M-27) was also detected in 29/31 strains. The isolate KP-s26 carried five circular plasmids. pA and pB were conjugate plasmids, as they carried drug resistance genes and contained a complete IV secretion system.Conclusion The blaKPC-2 carbapenemase gene is relatively conservative in the process of evolution; drug-resistant plasmids containing conjugated transfer elements contribute to the spreading of drug resistance. The coexistence of blaKPC-2 with fosA6 or blaCTX-M variants was associated with increased fosfomycin resistance and broad-spectrum β-lactam resistance, respectively.Clinical Trials Registration Clinical Trials.gov Identifier: NCT03950544
Yali Zhang,Mengyue Liu,Jiangfeng Zhang,Jie Wu,Lijuan Hong,LiQiang Zhu,Jinzhao Long
bla NDM-1 and bla KPC-2 are responsible for the global increase in carbapenem-resistant Klebsiella pneumoniae , posing a great challenge to public health. However, the impact of phylogenetic factors on the dissemination of bla NDM-1 and bla KPC-2 is not yet fully understood . This study established a global dataset of 4051 bla NDM-1 + and 10,223 bla KPC-2 + K. pneumoniae genomes, and compared their transmission modes on a global scale. The results showed that bla NDM-1 + K. pneumoniae genomes exhibited a broader geographical distribution and higher sequence type (ST) richness than bla KPC-2 + genomes, indicating higher transmissibility of the bla NDM-1 gene. Furthermore, bla NDM-1 + genomes displayed significant differences in ST lineage, antibiotic resistance gene composition, virulence gene composition and genetic environments compared with bla KPC-2 + genomes, suggesting distinct dissemination mechanisms. bla NDM-1 + genomes were predominantly associated with ST147 and ST16, whereas bla KPC-2 + genomes were mainly found in ST11 and ST258. Significantly different accessory genes were identified between bla NDM-1 + and bla KPC-2 + genomes. The preference for bla KPC-2 distribution across certain countries, ST lineages and genetic environments underscores vertical spread as the primary mechanism driving the expansion of bla KPC-2 . In contrast, bla NDM-1 + genomes did not display such a strong preference, confirming that the dissemination of bla NDM-1 mainly depends on horizontal gene transfer. Overall, this study demonstrates different phylogenetic drivers for the dissemination of bla NDM-1 and bla KPC-2 , providing new insights into their global transmission dynamics.
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