ArticlePLoS pathogens2023
Treponema pallidum subsp. pallidum with an Artificially impaired TprK antigenic variation system is attenuated in the Rabbit model of syphilis.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Global research trends in neurosyphilis: a bibliometric analysis from 2010 to 2024.Frontiers in immunology · 2025Pooled it
- Putative mechanisms of ocular inflammation in syphilis.Journal of ophthalmic inflammation and infection · 2026Review
- The Global Syphilis Epidemic: Turning the Tide.Sexually transmitted diseases · 2026Article
- Formal description ofInternational journal of systematic and evolutionary microbiology · 2026Article
- Lineage-specificbioRxiv : the preprint server for biology · 2026Article
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- Syphilis and Tuberculosis as Mimickers of Autoimmune Diseases: Diagnostic Overlap and Surveillance Implications in Mexico.Diseases (Basel, Switzerland) · 2025Review
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- High quality transcriptome profiling confirms the transcriptional landscape of Treponema pallidum subsp. pallidum.Scientific reports · 2025Article
- Establishment of the Nichols strain as the type strain ofInternational journal of systematic and evolutionary microbiology · 2025Review
- Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.ACS central science · 2025Review
- Development and utilization ofmBio · 2025Article
- Research Advances in Clinical Strategies and Preclinical Models for Syphilis Relapse.Infection and drug resistance · 2025Review
- Development and utilization ofbioRxiv : the preprint server for biology · 2024Article
- Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.Molecular microbiology · 2024Article
- Article
- Genomic Epidemiology of Treponema pallidum and Circulation of Strains With Diminished tprK Antigen Variation Capability in Seattle, 2021-2022.The Journal of infectious diseases · 2024Article
- Comprehensive Overview ofCurrent protein & peptide science · 2024Review
- Advancements in the development of nucleic acid vaccines for syphilis prevention and control.Human vaccines & immunotherapeutics · 2023Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe TprK protein of the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire of 53 silent chromosomal donor cassettes (DCs) into the single tprK expression site to continually generate TprK variants. Several lines of research developed over the last two decades support the theory that this mechanism is central to T. pallidum's ability for immune avoidance and persistence in the host. Structural and modeling data, for example, identify TprK as an integral outer membrane porin with the V regions exposed on the pathogen's surface. Furthermore, infection-induced antibodies preferentially target the V regions rather than the predicted β-barrel scaffolding, and sequence variation abrogates the binding of antibodies elicited by antigenically different V regions. Here, we engineered a T. pallidum strain to impair its ability to vary TprK and assessed its virulence in the rabbit model of syphilis. PRINCIPAL
findingsA suicide vector was transformed into the wild-type (WT) SS14 T. pallidum isolate to eliminate 96% of its tprK DCs. The resulting SS14-DCKO strain exhibited an in vitro growth rate identical to the untransformed strain, supporting that the elimination of the DCs did not affect strain viability in absence of immune pressure. In rabbits injected intradermally with the SS14-DCKO strain, generation of new TprK sequences was impaired, and the animals developed attenuated lesions with a significantly reduced treponemal burden compared to control animals. During infection, clearance of V region variants originally in the inoculum mirrored the generation of antibodies to these variants, although no new variants were generated in the SS14-DCKO strain to overcome immune pressure. Naïve rabbits that received lymph node extracts from animals infected with the SS14-DCKO strain remained uninfected.
conclusionThese data further support the critical role of TprK in T. pallidum virulence and persistence during infection.
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