Large-scale comparative analysis reveals phylogenomic preference of blaNDM-1 and blaKPC-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.