The Salmonella enterica PhoP Directly Activates the Horizontally Acquired SPI-2 Gene sseL and Is Functionally Different from a S. bongori Ortholog
Bibliographic record
Abstract
To establish a successful infection within the host, a pathogen must closely regulate multiple virulence traits to ensure their accurate temporal and spatial expression. As a highly adapted intracellular pathogen, Salmonella enterica has acquired during its evolution various virulence genes via numerous lateral transfer events, including the acquisition of the Salmonella Pathogenicity Island 2 (SPI-2) and its associated effectors. Beneficial use of horizontally acquired genes requires that their expression is effectively coordinated with the already existing virulence programs and the regulatory set-up in the bacterium. As an example for such a mechanism, we show here that the ancestral PhoPQ system of Salmonella enterica is able to regulate directly the SPI-2 effector gene sseL (encoding a secreted deubiquitinase) in an SsrB-independent manner and that PhoP plays a part in a feed-forward regulatory loop, which fine-tunes the cellular level of SseL. Additionally, we demonstrate the presence of conserved cis regulatory elements in the promoter region of sseL and show direct binding of purified PhoP to this region. Interestingly, in contrast to the S. enterica PhoP, an ortholog regulator from a S. bongori SARC 12 strain was found to be impaired in promoting transcription of sseL and other genes from the PhoP regulon. These findings have led to the identification of a previously uncharacterized residue in the DNA-binding domain of PhoP, which is required for the transcriptional activation of PhoP regulated genes in Salmonella spp. Collectively our data demonstrate an interesting interface between the acquired SsrB regulon and the ancestral PhoPQ regulatory circuit, provide novel insights into the function of PhoP, and highlight a mechanism of regulatory integration of horizontally acquired genes into the virulence network of Salmonella enterica.
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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) | 0.001 | 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) | 0.002 | 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".