Lineage-specific tprK diversification and Treponema pallidum transmission dynamics in Buenos Aires, Argentina

Syphilis rates are rising globally, with increases in congenital syphilis in South America particularly concerning. The characterization of contemporary South American Treponema pallidum (Tp) strains is crucial to syphilis vaccine development, yet few genomic epidemiology studies have focused on this region. Here, we performed whole genome sequencing (WGS) of Tp from Buenos Aires, Argentina, as well as deep sequencing of the hypervariable tprK locus, which is critical to Tp immune evasion.

People with primary, secondary, or congenital syphilis were enrolled at two clinics in Buenos Aires between October 2018 and January 2023, including individuals associated with intra-household transmission. Hybrid capture WGS was performed and a core genome phylogeny generated. K-mer-based methods using full-length tprK PacBio long reads were used to uncover differences in diversity and detect Tp transmission.

Tp genomes were recovered from 70 individuals in Buenos Aires and primarily belonged to globally dominant SS14 sublineage-1 and Nichols sublineage-8, as did Tp from Brazil (n=8). Peruvian samples (n=3) all belonged to sublineage-1. Two individuals from Argentina had co-infections with Nichols- and SS14-lineage strains. Macrolide resistance via A2058G occurred in 27/70 (38.6%) samples. Across 56 samples, tprK allelic diversity was significantly increased in secondary syphilis, oral lesions, and SS14-lineage strains compared to primary syphilis, anogenital lesions, and Nichols-lineage strains, respectively. Increased diversity in SS14-lineage strains is driven by an enhanced repertoire of V7-specific donor sequences. tprK sequences from intra-household transmissions were more similar than unrelated samples with identical core genomes.

Tp circulating in South America is closely related to dominant global sublineages. Increased tprK diversity in the SS14 lineage may influence Tp's ability to escape host immunity. tprK profiling is a promising tool to elucidate syphilis transmission networks. This study underscores the utility of genomics to yield insights into Tp pathogenesis.

Gates Foundation INV-036560 (A.S.); NIH/NIAID R01AI139265 (J.D.K).