Genetic Profiling of the Full-Length tprK Gene in Patients with Primary and Secondary Syphilis

Abstract

The resurgence of syphilis in both low- and high-income countries has attracted attention, and persistent infection by the pathogen has long been a research focus. The tprK gene, encoding the hypervariable outer membrane protein, is thought to be responsible for pathogen immune evasion and persistent infection.

Genomic Epidemiology of Treponema pallidum and Circulation of Strains With Diminished tprK Antigen Variation Capability in Seattle, 2021–2022

“…We first examined potential confounders and found no relationship between the number of unique high-confidence V regions per sample and the number of T. pallidum genome copies input to the tprK library prep replicates (Pearson coefficient r = 0.204; P = .27) ( Supplementary Figure 1 A ). There was also no difference in the number of unique V regions by lineage or clinical stage ( P > .05; Welch's t test) ( Supplementary Figure 1 B ), despite previous studies of full-length haplotypes showing increased diversity of tprK in secondary samples [ 9 , 30 ]. Furthermore, we did not see associations between the number of unique tprK V regions and patient race, biological sex, sexual preference, age, swab sample location, intravenous drug use, or methamphetamine use.…”

“…Given the slow evolutionary rate of the T. pallidum genome and faster rate of tprK gene conversion, it may be worthwhile to include tprK deep sequencing data in public health genomic investigations to achieve greater temporal resolution of T. pallidum relatedness. Greater tprK diversity is associated with secondary syphilis cases [ 9 , 30 ], and tprK diversity may be indicative of the time elapsed since infection and helpful for public health investigations. However, correlation with more granular clinical history and epidemiological information is required.…”