Longitudinal Variations in the Gene of Treponema pallidum in an Amoy Strain-Infected Rabbit Model.

Heterogeneous sequences have been hypothesized to be an important factor for persistent infection of Treponema pallidum subsp. (T. pallidum) in humans. Previous research has only explored diversity using a rabbit model infected with almost clonal isolates, which is inconsistent with the fact that infected human isolates contain multiple heterogeneous sequences. Here, we used the T. pallidum Amoy strain with heterogeneous sequences to establish a rabbit infection model and explore longitudinal variations in the gene under normal infection, immunosuppression treatment, and benzathine penicillin G (BPG) treatment using next-generation sequencing. The diversity of the gene was high in all three groups but was highest in the control group and lowest in the BPG group. Interestingly, the overall diversity of in all three groups decreased during infection, exhibiting a "more to less" trend, indicating that survival selection may be an important factor affecting variation in the later infection stage. BPG treatment appeared to reduce the diversity of but increased the frequency of predominant sequence changes, which might facilitate the escape of T. pallidum from the host immune clearance. Furthermore, the original predominant V region sequence did not disappear with disease progression but retained a relatively high proportion within the population, suggesting a new direction for -related vaccine research. This study provides insights into longitudinal variations within the highly heterogeneous gene sequences of T. pallidum and will contribute to further exploration of the pathogenesis of syphilis. The variations are an important factor in persistent T. pallidum infection. A nearly clonal isolate has been used previously to investigate the mechanism of gene variations; however, clinical T. pallidum isolates in infected humans exhibit multiple heterogeneous sequences. Here, we use next-generation sequencing to explore longitudinal variations in the gene under normal infection and immunosuppression and benzathine penicillin G treatment in a rabbit model infected with the Amoy strain with heterogeneous sequences. The overall diversity of in all three groups was high and decreased during infection, exhibiting a "more to less" trend. Benzathine penicillin G treatment reduced the diversity of but increased the frequency of predominant sequence changes. Moreover, the original predominant V region sequence did not disappear as the disease progressed but remained at a relatively high proportion within the population. The research results give us a new understanding about variation.