Phenol-soluble modulins alpha induce G2/M phase transition delay and impair immune response of eukaryotic cells
Bibliographic record
Abstract
Staphylococcus aureus is responsible for a wide range of infections in human and animals. We found that S aureus slowed down host cell proliferation and induced a cytopathic effect. We demonstrated that S aureus induced a G2/M phase transition delay in host cells, which was associated with accumulation of the cyclin-dependent kinase Cdk1/cdc2 and unphosphorylated histone H3. We found that a G2 phase delay was preferential for bacterial internalization and intracellular proliferation. Using size exclusion chromatography and mass spectroscopy analysis, we identified phenol-soluble modulin alpha (PSMα) peptides as the candidates for this effect. The implication of PSMα in cell cycle alteration was confirmed by testing of synthetic PSMα and by comparison of LACwt with the isogenic mutant LAC∆psm, which lacks the operon encoding PSMα. The delay was associated with a decrease of defensins expression in a G2 phase, suggesting that PSMα-induced G2/M phase transition delay deteriorates antibacterial state of the epithelial surface.Investigation of the response to Escherichia coli and S. aureus showed a higher expression of key cytokines IL-6, IL-8, as well as IL-32 (which is involved in dendritic cell maturation) in E. coli-infected host cells. Comparison of cytokines expression in response to LACwt with isogenic mutants, which lack the operon encoding PSMs, show that PSMs inhibit interleukins production, thus impair the innate and adaptive immune response during S. aureus infection. Therefore we show, that PSMs alter the host cell cycle, resulting in a reduction of defense response of host’ cells, that reveal a newly-identified mechanism for promoting infection.
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".