ArticlePLoS neglected tropical diseases2021
Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum.
Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Formal description ofInternational journal of systematic and evolutionary microbiology · 2026Article
- Review
- Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.Molecular microbiology · 2024Article
- In-Depth Proteome Coverage of In Vitro-CulturedJournal of proteome research · 2024Article
- Proteomic analysis of theFrontiers in microbiology · 2024Article
- Comprehensive Overview ofCurrent protein & peptide science · 2024Review
- Resurgence of syphilis: focusing on emerging clinical strategies and preclinical models.Journal of translational medicine · 2023Review
- Deep proteome coverage advances knowledge of Treponema pallidum protein expression profiles during infection.Scientific reports · 2023Article
- Advancements in the development of nucleic acid vaccines for syphilis prevention and control.Human vaccines & immunotherapeutics · 2023Review
- Review
- Syphilis vaccine: challenges, controversies and opportunities.Frontiers in immunology · 2023Review
- 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
- The immune response and protective efficacy of a potential DNA vaccine against virulent Pasteurella multocida.Journal, genetic engineering & biotechnology · 2021Article
- Recent Vaccines against Emerging and Tropical Infectious Diseases.Discoveries (Craiova, Romania)Review
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundAn effective syphilis vaccine should elicit antibodies to Treponema pallidum subsp. pallidum (T. p. pallidum) surface antigens to induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses of T. p. pallidum genes to identify putative outer membrane proteins (OMPs) resulted in a list of potential vaccine candidates, still very little is known about whether and how transcription of these genes is regulated during infection. This knowledge gap is a limitation to vaccine design, as immunity generated to an antigen that can be down-regulated or even silenced at the transcriptional level without affecting virulence would not induce clearance of the pathogen, hence allowing disease progression. PRINCIPAL
findingsWe report here that tp1031, the T. p. pallidum gene encoding the putative OMP and vaccine candidate TprL is differentially expressed in several T. p. pallidum strains, suggesting transcriptional regulation. Experimental identification of the tprL transcriptional start site revealed that a homopolymeric G sequence of varying length resides within the tprL promoter and that its length affects promoter activity compatible with phase variation. Conversely, in the closely related pathogen T. p. subsp. pertenue, the agent of yaws, where a naturally-occurring deletion has eliminated the tprL promoter region, elements necessary for protein synthesis, and part of the gene ORF, tprL transcription level are negligible compared to T. p. pallidum strains. Accordingly, the humoral response to TprL is absent in yaws-infected laboratory animals and patients compared to syphilis-infected subjects.
conclusionThe ability of T. p. pallidum to stochastically vary tprL expression should be considered in any vaccine development effort that includes this antigen. The role of phase variation in contributing to T. p. pallidum antigenic diversity should be further studied.
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