ArticlePLoS neglected tropical diseases2015
Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 43 citations in OpenAlex.
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- Advancements in the development of nucleic acid vaccines for syphilis prevention and control.Human vaccines & immunotherapeutics · 2023Review
- Red Blood Cell Lysis Pretreatment Can Significantly Improve the Yield of Treponema pallidum DNA from Blood.Microbiology spectrum · 2023Article
- Syphilis vaccine: challenges, controversies and opportunities.Frontiers in immunology · 2023Review
- The Outer Membrane Lipoprotein Tp0136 Stimulates Human Platelet Activation and Aggregation Through PAR1 to Enhance GFrontiers in immunology · 2022Article
- Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar.PLoS neglected tropical diseases · 2021Article
- Two Potential Syphilis Vaccine Candidates Inhibit Dissemination ofFrontiers in immunology · 2021Article
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- Investigation of syphilis immunology and Treponema pallidum subsp. pallidum biology to improve clinical management and design a broadly protective vaccine: study protocol.BMC infectious diseases · 2020Article
- Comparative genomics and full-length Tprk profiling of Treponema pallidum subsp. pallidum reinfection.PLoS neglected tropical diseases · 2020Article
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- Analysis of host cell binding specificity mediated by the Tp0136 adhesin of the syphilis agent Treponema pallidum subsp. pallidum.PLoS neglected tropical diseases · 2019Article
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- Complete genome sequences of two strains of Treponema pallidum subsp. pertenue from Indonesia: Modular structure of several treponemal genes.PLoS neglected tropical diseases · 2018Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Adherence-mediated colonization plays an important role in pathogenesis of microbial infections, particularly those caused by extracellular pathogens responsible for systemic diseases, such as Treponema pallidum subsp. pallidum (T. pallidum), the agent of syphilis. Among T. pallidum adhesins, TP0136 is known to bind fibronectin (Fn), an important constituent of the host extracellular matrix. To deepen our understanding of the TP0136-Fn interaction dynamics, we used two naturally-occurring sequence variants of the TP0136 protein to investigate which region of the protein is responsible for Fn binding, and whether TP0136 would adhere to human cellular Fn in addition to plasma Fn and super Fn as previously reported. Fn binding assays were performed with recombinant proteins representing the two full-length TP0136 variants and their discrete regions. As a complementary approach, we tested inhibition of T. pallidum binding to Fn by recombinant full-length TP0136 proteins and fragments, as well as by anti-TP0136 immune sera. Our results show that TP0136 adheres more efficiently to cellular Fn than to plasma Fn, that the TP0136 NH2-terminal conserved region of the protein is primarily responsible for binding to plasma Fn but that binding sites for cellular Fn are also present in the protein's central and COOH-terminal regions. Additionally, message quantification studies show that tp0136 is highly transcribed during experimental infection, and that its message level increases in parallel to the host immune pressure on the pathogen, which suggests a possible role for this protein in T. pallidum persistence. In a time where syphilis incidence is high, our data will help in the quest to identify suitable targets for development of a much needed vaccine against this important disease.
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