A macrophage-based screen identifies antibacterial compounds selective for intracellular <i>Salmonella</i> Typhimurium
Bibliographic record
Abstract
Abstract Salmonella Typhimurium ( S . Tm) evades the innate immune response by residing within host phagocytes. To identify inhibitors of intracellular S . Tm growth, we performed parallel chemical screens against S . Tm growing in macrophage-mimicking media and within macrophages. These screens identified novel antibacterials, and revealed that antibiotics with limited Gram-negative coverage are active against intracellular S . Tm. Screening of a S . Tm deletion library in the presence of one compound, metergoline, revealed that outer membrane perturbation enhanced activity in vitro . Combined with our observation of atypical cell surface characteristics of intracellular S . Tm, our work indicates that the bacterial outer membrane is permeabilized within macrophages. We show that metergoline targets the bacterial cytoplasmic membrane, and prolongs animal survival during a systemic S . Tm infection. This work highlights the predictive nature of intracellular screens for in vivo efficacy, and uncovers new aspects of bacterial physiology of intracellular S . Tm.
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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) | 0.000 | 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".