Intramolecular synergism and bacterial lysis regulation can explain the complex multi-domain architecture of the bacteriophage endolysin PlySK1249
Bibliographic record
Abstract
Abstract Endolysins are peptidoglycan hydrolases produced at the end of the bacteriophage (phage) replication cycle to lyse the host cell. Gram-positive phages endolysins come in a variety of multi-modular forms that combine different catalytic domains and may have evolved to adapt to their bacterial hosts. However, the reason why phage can adopt endolysin with such complex multidomain architecture is for the moment not well understood. We used the Streptococcus dysgalactiae phage endolysin PlySK1249 as a model to study the implication of multi-domain architecture in phage-induced bacterial lysis and lysis regulation. The activity of the enzyme relied on a bacteriolytic amidase (Ami), a non-bacteriolytic L-Ala-D-Ala endopeptidase (CHAP) acting as a de-chaining enzyme and central LysM cell wall binding domain (CBD). Ami and CHAP synergized for peptidoglycan digestion and bacteriolysis in the native enzyme or when expressed individually and reunified in vitro . This cooperation could be modulated by bacterial cell wall-associated proteases, which specifically cleaved the two linkers connecting the different domains. While both catalytic domains were observed to act coordinately to optimize bacterial lysis, the CBD is expected to delay diffusion of the enzyme until proteolytic inactivation is achieved. As for certain autolysins, PlySK1249 cleavage by bacterial cell wall associated proteases might be an example of dual phage-bacterial regulation and mutual coevolution. In addition, understanding more thoroughly the multidomain interplay of PlySK1249 opens new perspectives on the ideal architecture of therapeutic antibacterial endolysins.
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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".