Large-scale comparative analysis reveals phylogenomic preference of bla NDM-1 and bla KPC-2 transmission among Klebsiella pneumoniae.

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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