O02.5 Secreted Proteolytic Activity of Bacterial Vaginosis-Associated Bacteria
Bibliographic record
Abstract
Bacterial vaginosis (BV) is a prevalent dysbiotic vaginal condition associated with increased risk for acquisition/transmission of sexually transmitted infections (STIs). While the microbes present in women with BV are highly variable, functional features such as increased catabolism of peptides/amino acids are relatively conserved. To date, the bacterial proteases initiating this process and identity of host protein targets remain undefined. We hypothesized that broad-acting proteases are secreted by BV-associated bacteria and modulate host factors relevant to STI acquisition. Bacterial suspensions and cell-free supernatants from select BV-associated species were evaluated for proteolytic activity using the universal protease substrate, casein, in agar plates and fluorometric assays. Degradation of collagen was explored using zymography or fluorophore-conjugated collagen with or without inhibitors. Fibrinogen/thrombin degradation was explored through clot inhibition assays and protein gel electrophoresis. Our investigations reveal that BV-associated bacteria including Prevotella amnii, Prevotella bivia, Porphyromonas asaccharolytica, Porphyromonas uenonis, Sneathia amnii, Sneathia sanguinegens, Gardnerella vaginalis, and Gardnerella piotti produce secreted proteases with broad substrate specificity. However, only select species degrade specific host protein polymers, namely collagen. Further investigation of Porphyromonas enzymes revealed that metallo- and cysteine proteases coordinate broad activity. Both species secrete three collagenases, which were fully abrogated by metalloprotease inhibitors in P. uenonis, but not P. asaccharolytica. Finally, both species degrade fibrinogen and thrombin to abrogate blood clotting. These studies reveal proteolytic activity is conserved among numerous vaginal bacteria with important roles in BV pathogenesis. However, modulation of specific host targets is more variable. Vaginal Prevotella and Porphyromonas species increase risk of HIV acquisition and our findings show Porphyromonas species exhibit proteolytic activities through diverse and redundant enzymes. These activities could induce barrier disruption and microhemmorrhage in the cervicovaginal niche, thereby increasing the risk of STI acquisition. Further characterization of secreted proteases and their targets could identify new therapeutics for BV and STIs.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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 | 0.000 |
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".