[1]Shanghai Skin Disease Hospital, STD Institute,Shanghai,China
[2]Fudan University, Oncology Bioinformatics Center,Shanghai,China
[3]Wenzhou Medical College, School of Laboratory Medicine,Wenzhou,China
[4]Wenzhou Medical University, School of Laboratory Medicine,Hangzhou,China
[5]Shanghai Skin Disease Hospital, Sexually Transmitted Disease Institute,Shanghai,China
[6]Tongji University, Shanghai Skin Disease Hospital,Shanghai,China
[7]Chinese National Human Genome Center at Shanghai, Shanghai-MOST Key Laboratory of Health and Disease Genomics,Shanghai,China
[8]1st Affiliated Hospital of Kunming Medical University, Department of Oncology,Kunming,China
Syphilis is a systemic sexually transmitted disease caused by Treponema pallidum ssp. pallidum (TPA). The origin and genetic background of Chinese TPA strains remain unclear. We identified a total of 329 single-nucleotide variants (SNVs) in eight Chinese TPA strains using next-generation sequencing. All of the TPA strains were clustered into three lineages, and Chinese TPA strains were grouped in Lineage 2 based on phylogenetic analysis. The phylogeographical data showed that TPA strains originated earlier than did T. pallidum ssp. pertenue (TPE) and T. pallidum ssp. endemicum (TPN) strains and that Chinese TPA strains might be derived from recombination between Lineage 1 and Lineage 3. Moreover, we found through a homology modeling analysis that a nonsynonymous substitution (I415F) in the PBP3 protein might affect the structural flexibility of PBP3 and the binding constant for substrates based on its possible association with penicillin resistance in T. pallidum. Our findings provide new insight into the molecular foundation of the evolutionary origin of TPA and support the development of novel diagnostic/therapeutic technology for syphilis.