Integrated genomic approaches improve Treponema pallidum phylogenetics and lineage classification.

Syphilis cases have been consistently rising since its near elimination in the late 1990s. This resurgence, along with increasing rates of macrolide resistance and congenital syphilis, has triggered renewed efforts to better understand and control the disease. We analyzed 827 Treponema pallidum genomes and created a new genome-based hierarchical lineage framework, recapitulating the major T. pallidum lineages and characterizing sub-lineages. An updated pangenome was constructed, revealing that T. pallidum subsp. pallidum lineages are determined by a single hypothetical major outer sheath C-terminal domain-containing gene, while no significant genetic difference was observed between T. pallidum subsp. pertenue and T. pallidum subsp. endemicum. This study introduces an integrated genomic approach to characterize T. pallidum and highlights the significance of pangenomes in supporting public health.