Global phylogenomics of Bordetella pertussis ST2 reveals regional heterogeneity in China and lineage-specific genome...

Bordetella pertussis sequence type 2 (ST2) is widely detected in China and in public genome datasets, yet the evolutionary relationships, dissemination patterns, and genomic features that distinguish its major lineages have not been systematically characterized.

In this study, we conducted a comprehensive genomic analysis of 580 ST2 genomes from 24 countries between 1942 and 2024, integrating 46 newly sequenced clinical isolates from Wenzhou, China. Phylogenetic reconstruction showed that the Wenzhou isolates were not homogeneous but comprised two distinct clades, including a dominant macrolide-resistant ptxP1-associated lineage and a smaller ptxP3-associated lineage. At the global scale, the ST2 population resolved into two major clades and three subclades; the dominant ptxP1-associated Wenzhou lineage was assigned to subclade I, whereas the smaller ptxP3-associated Wenzhou lineage belonged to global clade II, with one isolate placed in subclade III. Two China-enriched subclades were strongly associated with 23S rRNA A2047G mutations, whereas a geographically widespread subclade lacked this determinant. Chinese isolates were distributed across multiple phylogenetic positions, supporting repeated introductions followed by local expansion. Comparative analyses further revealed lineage-specific differences in detected insertion sequence (IS) elements and pseudogene accumulation. IS481 was the predominant IS family, and intergenic insertions were more common than intragenic events across lineages. Clade-specific SNPs and stable pseudogene patterns together indicated partially distinct adaptive trajectories among ST2 clades.

These findings define the local and global population structure of ST2, highlight marked regional heterogeneity in contemporary Chinese pertussis, and show that ongoing diversification of this lineage is shaped by both geographic spread and lineage-specific genome evolution.