Stable Signal Peptides and the Response to Secretion Stress in <i>Staphylococcus aureus</i>
Bibliographic record
Abstract
ABSTRACT Protein secretion is essential, but how it is managed is poorly understood. In bacteria, most secreted proteins require release from the outer surface of the cytoplasmic membrane by type I signal peptidase (SPase), which cleaves the mature protein from its membrane-bound N-terminal signal peptide. As the first step that occurs outside the protected cytoplasmic environment and because insufficient activity can rapidly result in the toxic accumulation of preproteins, the activity of SPase is expected to be closely monitored and perhaps supplemented when insufficient. Indeed, we previously demonstrated that inhibition of SPase in Staphylococcus aureus results in derepression of the ayrRABC operon, which encodes an alternate mechanism to release proteins. However, in this case, the proteins are released with partially intact signal peptides, with the exception of IsaA, which is released with a virtually intact signal peptide. Here we show that mutation of AyrA [ ayrA (R233K)] results in constitutive derepression of ayrRABC and that mutation of IsaA’s signal peptide [ isaA (K2Q)] results in hyperderepression upon SPase inhibition, which also requires AyrA. Further studies demonstrate that the inducing signal for ayrRABC derepression is accumulation of a subset of preproteins with signal peptides that are stable toward further processing and that the signal is critically amplified by the K2Q mutation and relayed to AyrR by AyrA. These results elucidate the mechanism by which S. aureus monitors and responds to secretion stress. The presence of ayrRA in other bacteria suggests that it may represent a general strategy linking membrane stress to appropriate transcriptional responses. IMPORTANCE Bacteria interact with their environment by secreting proteins that perform a myriad of functions, and the final step is the release of the mature protein from the cell surface via the activity of type I signal peptidase (SPase). While the bacterial response to many stresses is understood in some detail, almost nothing is known about how cells respond to secretion stress, such as insufficient SPase activity, which would eventually result in cell death. We previously demonstrated that the inhibition of SPase in Staphylococcus aureus results in the derepression of the ayrRABC operon, which can functionally replace SPase, but which is normally repressed by AyrR. We now demonstrate that the inducing signal for derepression is accumulation of a subset of preproteins with signal peptides that are stable to further processing and that the signal is relayed to AyrR via AyrA.
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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 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".