Large-scale comparative analysis reveals phylogenomic preference of blaNDM-1 and blaKPC-2 transmission among Klebsiella pneumoniae

blaNDM-1 and blaKPC-2 are responsible for the global rise of carbapenem-resistant K. pneumoniae, posing a great challenge to public health. However, the impact of phylogenetic factors on blaNDM-1 and blaKPC-2 dissemination is not yet fully understood. Here, we established a global dataset of 4051 blaNDM-1+ or 10223 blaKPC-2+ K. pneumoniae genomes and compared their transmission mode on a global scale. The results showed that blaNDM-1+ K. pneumoniae genomes exhibited a broader geographical distribution and higher ST richness than blaKPC-2+, indicating higher transmissibility of the blaNDM-1 gene. Furthermore, blaNDM-1+ genomes displayed significant difference in ST lineage, antibiotic resistance genes composition, virulence genes composition, genetic environments with blaKPC-2+, suggesting their distinct dissemination mechanism. blaNDM-1+ genomes were predominantly associated with ST147 and ST16, whereas blaKPC-2+ genomes were mainly found in ST11 and ST258. Significantly different accessory genes were identified between blaNDM-1+ and blaKPC-2+ genomes. The preference for blaKPC-2 distribution across certain countries, ST lineages, and genetic environments underscores vertical spread as the primary mechanism driving the expansion of blaKPC-2. In contrast to blaKPC-2+, blaNDM-1+ genomes did not display such a strong preference, confirming that the blaNDM-1 dissemination mainly depended on horizontal gene transfer. Overall, our study demonstrates different phylogenetic drivers of blaNDM-1 and blaKPC-2 dissemination, providing new insights into their global transmission dynamic.