Vanillin inhibits PqsR-mediated virulence in <i>Pseudomonas aeruginosa</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
Reduced efficacy of antibiotics in bacterial diseases is a global concern in clinical settings. Development of anti-virulence compounds which disarm bacterial virulence is an attractive therapeutic agent for complementary antibiotics usage. One potential target for anti-virulence compounds is quorum sensing (QS), the intercellular communication system in most pathogens, such as Pseudomonas aeruginosa. QS inhibitors (QSIs) can inhibit QS effectively, attenuate QS-mediated virulence, and improve host clearance of infections. While studies focused on developing homoserine-based las QSI, few targeted the quinolone-based pqs QS, which implicated host cytotoxicity and biofilm formation. It is imperative to develop novel anti-pqs-QS therapeutics for combinatorial antibiotic treatment of microbial diseases. We employed a gfp-based transcriptional pqs biosensor to screen a natural compounds library and identify vanillin (4-hydroxy-3-methoxybenzaldehyde), the primary phenolic aldehyde of vanilla bean. The vanillin inhibited pqs expression and its associated phenotypes, namely pyocyanin production and twitching motility in P. aeruginosa. Molecular docking results revealed that vanillin binds to the active site of PqsR, the PQS-binding response regulator. Combinatorial treatment of vanillin with antimicrobial peptide (colistin) inhibited biofilm growth in vitro and improved treatment in the in vivo C. elegans acute infection model. We demonstrated that vanillin could dampen pqs QS and associated virulence, thus providing novel therapeutic strategies against P. aeruginosa infections.
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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 | 0.000 |
| 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) | 0.000 | 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 it