Effect of Lipid Length and Cationic Residues on the Antibacterial and Hemolytic Activities of Paenibacterin
Bibliographic record
Abstract
Paenibacterin A1 (PA1) is a broad-spectrum, cationic cyclic lipodepsipeptide antibiotic isolated from Paenibacillus thiaminolyticus. In this study, the roles of the cationic residues and lipid tail length on the in vitro antibacterial and hemolytic activities of PA1 was examined in the context of an active PA1 analogue, called PAK, in which the two D-Orn residues in PA1 were converted to D-Lys residues. The effect of reducing the length of the lipid tail in PAK from 15 to 12–10 carbons on the minimum inhibitory concentration (MIC) depended upon the bacteria. This change had little effect on the MIC against Escherichia coli and Bacillus subtilis but resulted in a reduction in activity against most of the ESKAPE pathogens tested with the exception of Klebsiella pneumoniae. Any one of the four cationic residues in PAK could be replaced with alanine with only a minimal effect on its MIC against B. subtilis, E.coli, K. pneumoniae, Acinetobacter baumannii, and MSSA. For Pseudomonas aeruginosa and the two MRSA strains tested, the presence of cationic residues at positions 7 and 12 are not important for activity, while the cationic residues at positions 1 and 4 are important. While PAK exhibited some hemolysis at 8 μg/mL and 70% hemolysis at 128 μg/mL, its C-12 and C-10 analogues were not hemolytic up to 128 μg/mL. All PAK analogues that had one or two cationic residues replaced with alanine were as hemolytic as or more hemolytic than PAK.
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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) | 0.000 | 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 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".