O16.6 Basic science aids syphilis vaccine development: bloodstream spreading by the syphilis spirochete<i>treponema pallidum</i>
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
<h3>Background</h3> <i>Treponema pallidum</i> ssp. <i>pallidum</i> (<i>Tp</i>) causes syphilis, a sexually transmitted infection characterized by multi-stage disease and diverse symptoms<i>. Tp</i> 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 <i>Tp</i> that mediates adherence to endothelial cells (ECs) lining blood vessel walls. This study explores <i>Tp</i> movement across endothelial barriers to enhance our understanding of <i>Tp</i> dissemination and identify host interactions that could be targeted for vaccine development. <h3>Methods</h3> 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. <h3>Results</h3> Here we show <i>Tp</i> 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 <i>Neisseria meningitidis</i> and <i>Streptococcus pneuomoniae</i>. Further molecular analyses reveal that <i>Tp</i> 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. <h3>Conclusion</h3> 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 <i>Tp</i> barrier traversal reveals that <i>Tp</i> 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 <i>Tp</i> infection and facilitate targeted syphilis vaccine development. <h3>Disclosure</h3> No significant relationships.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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 it