Modulation of the Regulatory Activity of Bacterial Two-component Systems by SlyA
Bibliographic record
Abstract
Activation of the transcriptional regulator SlyA by the PhoP/PhoQ two-component system controls intracellular expression of numerous factors influencing Salmonella virulence. By dissecting the SlyA regulon using stable isotope labeling with amino acids in cell culture analysis, we found that SlyA enhances overall transcription of PhoP-activated loci. This amplification of cellular responses to Mg2+ occurs when SlyA binds to the phoPQ promoter thereby activating phoP autoregulation via a positive feedback mechanism. SlyA footprints a DNA region located one helical turn upstream of the PhoP box, which overlaps the H-NS-binding motif required for signal-dependent phoP repression in high Mg2+ conditions. Therefore, binding of SlyA likely antagonizes H-NS and facilitates the interaction of PhoP to its own promoter, subsequently activating the phoPQ operon. Establishment of this regulatory circuit allows SlyA to exert its effect on the PhoP/PhoQ system specifically in Salmonella, which may confer an additional transcriptional regulation. Thus, our results provide a molecular mechanism that determines SlyA-dependent activation of PhoP-regulated genes in modulating Salmonella virulence. Evidence from this study also suggests a function of SlyA as a mediator in signal transduction from the PhoP/PhoQ system to other bacterial two-component systems in Salmonella.
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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".