Antimicrobial Activity Of A Histone Derived Peptide In The Airway Surface Liquid
Bibliographic record
Abstract
Extracellular histones are viewed as cytotoxic markers in cell death, apoptosis and NETosis. However, extracellular histones have been found to carry out a number of roles outside their function as a damage associated molecular patterns to signal cell death. Extracellular histones have been seen to act as an early release marker of cell stress, influence cell growth, have antimicrobial activity and bioactive peptides. A suggested method for the intentional secretion of histones has been show through amphisomes, with histones being present in the proteome of healthy biological systems. Airway surface liquid (ASL), present in the lumen of the airways plays a critical role in airway defense and innate immunity. We identified a number of histone derived peptides by de novo peptide sequencing of the airway surface liquid. In ASL overlying H441, Calu3 and BMI‐1 transduced human bronchial epithelial cells (HBEC) we identified similar histone peptides. This was supported by their presence in sputum samples from people with and without Cystic Fibrosis disease. To test whether the ASL histone peptides had a bioactive role we produced synthetic analogues using SPOT peptide synthesis. The peptides were then tested for effects on human embryonic kidney (HEK 293) cell growth, viability and intracellular Ca 2+ [Ca2+]i. One candidate, MAT9 when screened suppressed the rise in [Ca2+]i in response to thapsigargin (p=0.001, n=8 with 16 replicates), but did not affect cell viability or cell growth. When MAT9 (10µM) was tested on H441 airway epithelial cells, it increased the thapsigargin‐induced rise in [Ca2+]i (P=0.01, n=6, with 12 replicates). This difference in calcium response could be due to a lack of toll‐like receptors (known receptors for histone proteins) in HEK cells which are present in H441 cells. Alongside this MAT9 (10µM) inhibited growth of luminescent Pseudomonas aeruginosa and was able to significantly reduce the growth rate over 4 hours at 5µM (P=0.01, n=4, with 16 replicates). Outside of this antibacterial activity, preliminary data showed some activity against Sars‐Cov2 replication in Caco‐2 cells. This data indicates that MAT9 is a histone derived peptide with bioactivity, and its proline‐alanine sequence may represent a chance to enhance this activity by changing its isomerization.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".