The Salmonella phage shock protein system is required for defense against host antimicrobial peptides
Bibliographic record
Abstract
Macrophages are professional phagocytes that play a major role in engulfing and eliminating invading pathogens. Some intracellular pathogens, such as Salmonella enterica serovar Typhimurium, exploit macrophages as niches for their replication, which requires precise and dynamic modulation of bacterial gene expression in order to resist the hostile intracellular environment. Here, we present a comprehensive analysis of the global transcriptome of S. Typhimurium across four stages of infection of primary macrophages. Our results revealed a profound change in early-stage gene expression dominated by pathways linked to metabolic processes required for Salmonella adaptation to the proinflammatory conditions of the macrophage. We identified the phage shock protein (Psp) system to be highly expressed in intracellular S. Typhimurium, with sustained high expression over the course of infection. We determined that the Psp system is regulated by the virulence-associated two-component system SsrA-SsrB, which coordinates its expression with critical bacterial functions required for immune evasion and intracellular survival. Functional assays demonstrated that the Psp system mediates resistance to host antimicrobial peptides, including cathelicidin-related antimicrobial peptide (CRAMP), which we demonstrate supports bacterial persistence in host tissues and survival within macrophages. Our findings establish the Psp system as a new and critical adaptive mechanism for evading host immune defenses and highlight the utility of temporal transcriptomics in unraveling the genetic strategies employed by S. Typhimurium during macrophage infection.
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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 | 0.001 | 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".