Daptomycin Pore Formation Is Restricted by Lipid Acyl Chain Composition
Bibliographic record
Abstract
Daptomycin is a calcium-dependent lipopeptide antibiotic that is used clinically against various Gram-positive pathogens. It acts on bacterial cell membranes, whose susceptibility varies with the content of phosphatidylglycerol (PG). Some studies have reported that daptomycin permeabilizes and depolarizes bacterial cell membranes, while others have found no evidence of membrane permeabilization and thus proposed different mechanisms of antibacterial action. Divergent observations have also been reported regarding the effect of daptomycin on model membranes, which were found to be permeabilized nonselectively, selectively for small cations, or not at all. While these diverging model studies did consider the functional roles of different lipid head groups, they assumed that the acyl chains were interchangeable. We here show this assumption to be erroneous. In equimolar mixtures of PG and phosphatidylcholine (PC), dimyristoyl lipids support membrane permeabilization, whereas dioleyl and palmitoleyl lipids do not, even though daptomycin does bind to and form oligomers on all of these membranes. These observations help reconcile some of the discrepant findings in the literature.
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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".