Evolutionary History of Treponema pallidum subsp. pertenue: Insights into Host Ancestry and Cross-Species Transmission

Treponema pallidum, a bacterium from the Spirochaetota phylum, is responsible for treponematoses, such as syphilis, yaws, bejel, and pinta. Different subspecies of this bacterium cause each of these diseases. This study focuses on Treponema pallidum subsp. pertenue (TPE), which causes yaws in humans and is primarily transmitted through direct contact with skin lesions, mainly affecting children and preadolescents. If untreated, it can progress to severe deformities in bones and cartilage. During the 20th century, significant progress was made in the eradication and control of this disease. However, in recent decades, there has been an increase in the number of reported cases. Until recently, it was believed that this subspecies affected only humans, but recent studies have identified that non-human primates (NHPs) have also been naturally infected with TPE. Considering the impacts of this disease on both humans and other species, TPE has become a focus of surveillance and scientific investigation. This study aims to clarify the relationship between infection in humans and other primate species, contributing to a better understanding of transmission dynamics and potential control and prevention strategies. To achieve this, we used genome sequences from 58 TPE strains (24 from humans and 19 from NHPs) available in public repositories and applied phylogenetic analyses and computational tools for recombinant region detection. The phylonetic analysis demonstrated a rapid expansion of the subspecies at the base of the tree and clustered the samples into nine groups. No groups contained both human and NHP samples, indicating that interactions between the two sample groups are rare or nonexistent. Recombination analyses detected only one region where an NHP sample may have recombined with a human sample. The application of the molecular clock in phylogenetic inference indicated a recent origin of TPE in 1885. The study of trait evolution further suggests that the host of the most recent common ancestor of TPE was humans. The analyses conducted in this study provided deeper insights into the spread of the disease and its interaction across different species.