A dual-tier plasmid network model underpins the evolutionary success of pandemic Klebsiella pneumoniae ST11
摘要
The convergence of antimicrobial resistance and hypervirulence in high-risk Klebsiella pneumoniae clones represents a major public health threat. However, evolutionary mechanisms enabling specific lineages to achieve pandemic dominance remain unclear. In this study, we integrated pangenomics and network analysis across 1,010 complete genomes from 38 countries. Species-wide dynamics revealed an extremely open pangenome (α = 0.59). In contrast, the dominant ST11 lineage, representing 30% of isolates, exhibited extremely low within-lineage phylogenetic diversity, consistent with a recent clonal expansion concentrated in East Asia. The East Asian ST11 lineage exhibited the lowest pangenome diversity (α = 0.86) associated with fixation of persistence and plasmid-stabilization systems and purging of redundant defense mechanisms. This configuration sustains a dual-tier plasmid network comprising a lineage-anchored IncFII(pHN7A8) replicon for vertical stability alongside high-connectivity hubs such as IncFIB(K) facilitating horizontal gene transfer. Chromosomal integration and tandem amplification of key resistance determinants (blaKPC−2, blaCTX−M−15) further reinforced this architecture. Consequently, 34.2% of isolates exhibited convergence of carbapenem resistance and hypervirulence. Within the East Asian ST11 clade, two dominant sub-lineages emerged: KL47:O13 (25.5%) and KL64:O2α (72%). Despite lower IncFII(pHN7A8) penetrance, KL64 became the dominant sub-lineage, indicating that factors beyond plasmid carriage, possibly including surface antigen properties, contribute to its epidemiological success. These findings indicate that ST11 success arises from synergy between species-wide pangenome openness and lineage-specific genomic optimization, and highlight plasmid network topology as a complementary framework for genomic surveillance of adaptive clonal expansion.