<i>Pseudomonas aeruginosa</i> quorum‐sensing homoserine lactone inhibits O <sub>2</sub> consumption and stimulates H <sup>+</sup> secretion by airway epithelia (869.2)
Bibliographic record
Abstract
P. aeruginosa biofilms accumulate in the airways of cystic fibrosis patients and produce the quorum‐sensing molecule N‐(3‐oxododecanoyl)‐homoserine lactone (C12) that depolarizes mitochondria. We tested whether C12 and P. aeruginosa biofilms change O 2 consumption and H + secretion into the extracellular fluid of JME (CF nasal epithelia, ΔF508CFTR) and CFTR‐corrected JME cells studied in Seahorse X24‐well dishes. C12 caused dose‐dependent (min = 1 µM, max = 50 µM) inhibition of O 2 consumption (to 0.6x control) and increases in H + secretion (to 1.3x control), similar to effects of mitochondrial poisons antimycin + rotenone. As measured by pH‐stat, C12 increased H + secretion into the apical solution of human tracheal epithelial (HTE) cells in primary culture by 0.3 µeq . cm ‐2. hr ‐1 , similar to rates measured using Seahorse. H + secretion by HTE cells was blocked by Zn 2+ . PAO1wt biofilms inhibited O 2 consumption and increased H + secretion by JME cells, while PAO1lasI biofilm and planktonic PAO1wt did not. JME and CFTR‐corrected JME cells behaved similarly during all treatments. These data indicated: (i) P. aeruginosa biofilms, most likely operating through C12, inhibit O 2 consumption and stimulate H + secretion by airway epithelia. (ii) H + secretion occurs through a Zn 2+ ‐sensitive H + channel in the apical membrane. (iii) Although there is no direct role for CFTR in these processes, a downward spiral in CF is predicted: increased acidity in CF ASL (no HCO 3 secretion) → reduced antimicrobial factors → P. aeruginosa accumulation in biofilms → inhibit mitochondrial metabolism and increase anaerobic glycolysis in epithelia → increased epithelial secretion of H + → increased acidity in ASL → reduced antimicrobial factors → increased P. aeruginosa accumulation. Grant Funding Source : NIH, CFRI
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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) | 0.002 | 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 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".