O16.6 Basic science aids syphilis vaccine development: bloodstream spreading by the syphilis spirochete<i>treponema pallidum</i>
Bibliographic record
Abstract
Background Treponema pallidum ssp. pallidum (Tp) causes syphilis, a sexually transmitted infection characterized by multi-stage disease and diverse symptoms. Tp undergoes rapid vascular dissemination, penetrating tissue, placental, and blood-brain barriers to access secondary infection sites via a process that is incompletely understood. The protein Tp0751 is an adhesin on the host-facing surface of Tp that mediates adherence to endothelial cells (ECs) lining blood vessel walls. This study explores Tp movement across endothelial barriers to enhance our understanding of Tp dissemination and identify host interactions that could be targeted for vaccine development. Methods The methods of affinity chromatography and proteomics were used to identify receptor proteins on host ECs that are bound by Tp0751. Antibody inhibition studies revealed specific receptor regions required for binding. Endothelial barrier traversal was investigated with immunofluorescence and barrier permeability assays. Phosphoproteomics identified endothelial intracellular signaling pathways initiated by Tp0751 by exploring gain/loss of phosphoryl groups on proteins. Results Here we show Tp uses Tp0751 to bind the 67 kDa laminin receptor (LamR) on human EC surfaces. Importantly, the same region of LamR is also targeted by meningitis-causing bacteria including Neisseria meningitidis and Streptococcus pneuomoniae. Further molecular analyses reveal that Tp and Tp0751 disrupt the architecture of human cell-cell junctions in blood vessel walls without altering overall barrier integrity. Phosphoproteomics demonstrates that ECs exposed to Tp0751 exhibit differential phosphorylation on proteins known to promote endothelial barrier traversal by leukocytes and pathogens. Conclusion These studies suggest a common tissue invasion strategy exists for neuroinvasive pathogens and identifies an interaction that can guide vaccine development for syphilis and other neuroinvasive diseases. Further, exploring Tp barrier traversal reveals that Tp uses similar mechanisms as immune cells and neurotropic pathogens to invade tissues and cause the detrimental sequelae associated with syphilis. These studies enhance our understanding of Tp infection and facilitate targeted syphilis vaccine development. Disclosure No significant relationships.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.108 | 0.049 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".