Oncotarget

Research Papers: Pathology:

Tracing the origin of Treponema pallidum in China using next-generation sequencing

Jun Sun, Zhefeng Meng, Kaiqi Wu, Biao Liu, Sufang Zhang, Yudan Liu, Yuezhu Wang, Huajun Zheng, Jian Huang and Pingyu Zhou _

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Oncotarget. 2016; 7:42904-42918. https://doi.org/10.18632/oncotarget.10154

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Abstract

Jun Sun1,*, Zhefeng Meng2,*, Kaiqi Wu3, Biao Liu3, Sufang Zhang4, Yudan Liu4, Yuezhu Wang5, Huajun Zheng5, Jian Huang5,6 and Pingyu Zhou1,4

1 STD Institute, Shanghai Skin Disease Hospital, Shanghai, China

2 Oncology Bioinformatics Center, Minhang Hospital, Fudan University, Shanghai, China

3 School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China

4 Shanghai Skin Disease Hospital, Clinical School of Anhui Medical University, Shanghai, China

5 Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China

6 Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Pingyu Zhou, email:

Jian Huang, email:

Keywords: Treponema pallidum, syphilis, NGS, SNVs, evolution, Pathology Section

Received: December 20, 2015 Accepted: June 01, 2016 Published: June 17, 2016

Abstract

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.


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