A54145 Factor D Is Not Less Susceptible to Inhibition by Lung Surfactant than Daptomycin
Bibliographic record
Abstract
A54145 factor D (A5D) is a cyclic lipopeptide antibiotic that shares several structural and mechanistic features with the clinically important antibiotic daptomycin, such as their requirement for calcium and phosphatidylglycerol (PG) for activity. Studies by others have suggested that daptomycin’s activity is strongly inhibited by lung surfactant while A5D’s activity is not. This finding has inspired efforts, albeit unsuccessful, to develop an A5D analogue that is highly active in the presence of lung surfactant and can be used for treating community acquired pneumonia (CAP). Here we demonstrate that A5D, like daptomycin, has a strong preference for the 1,2-diacyl-sn-glycero-3-phospho-1′-sn-glycerol stereoisomer (2R,2′S configuration) of PG. This PG stereoisomer was determined to be the only stereoisomer of PG in lung surfactant. Both antibiotics are completely antagonized by approximately 1–2 mol equiv of 2R,2′S-PG. Studies performed in the presence of lung surfactant revealed that the antagonism of these peptides by surfactant is mainly due to their interaction with PG and that A5D is not significantly less susceptible to inhibition by lung surfactant than daptomycin.
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How this classification was reachedexpand
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) | 0.003 | 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 teacher head, 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".