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

bla and bla 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 and bla is not yet fully understood This study established a global dataset of 4051 bla+ and 10,223 bla+ K. pneumoniae genomes, and compared their transmission modes on a global scale. The results showed that bla+ K. pneumoniae genomes exhibited a broader geographical distribution and higher sequence type (ST) richness than bla+ genomes, indicating higher transmissibility of the bla gene. Furthermore, bla+ genomes displayed significant differences in ST lineage, antibiotic resistance gene composition, virulence gene composition and genetic environments compared with bla+ genomes, suggesting distinct dissemination mechanisms. bla+ genomes were predominantly associated with ST147 and ST16, whereas bla+ genomes were mainly found in ST11 and ST258. Significantly different accessory genes were identified between bla+ and bla+ genomes. The preference for bla distribution across certain countries, ST lineages and genetic environments underscores vertical spread as the primary mechanism driving the expansion of bla. In contrast, bla+ genomes did not display such a strong preference, confirming that the dissemination of bla mainly depends on horizontal gene transfer. Overall, this study demonstrates different phylogenetic drivers for the dissemination of bla and bla, providing new insights into their global transmission dynamics.