Elongation Factor P-Dependent Translation and Metabolic Phenotypes of Salmonella
Bibliographic record
Abstract
The facultative intracellular pathogen Salmonella has acquired adaptations contributing to virulence, including pathogenicity islands and regulatory alterations. Elongation factor P (EF-P) is a universally conserved translation factor, and deletion of efp in Salmonella results in pleiotropic phenotypes, including hyperactive metabolism, reduced stress resistance, and avirulence. Crystal structures demonstrated that EF-P adopts the shape of a tRNA and binds to the ribosome to stimulate peptide bond synthesis. Preliminary analyses suggested that EF-P is not a general translation factor but rather influences a specific subset of proteins. In this thesis I investigate the mechanism underlying EF-Pâ s impact on translation and how its deletion leads to the observed phenotypes. I present the Salmonella EF-P-dependent proteome, and particular proteins offer explanations for efp mutant phenotypes. Meanwhile, other groups discovered that EF-P rescues ribosomes stalled at polyproline motifs. I expand upon their work and show that polyproline motifs are not strictly necessary or solely sufficient to render a protein dependent on EF-P. I demonstrate that residues upstream of the polyproline motif significantly influence stall strength. Furthermore, translation initiation rate greatly impacts EF-P-dependence. I present a model wherein elongation stalls only reduce protein synthesis if they are more rate-limiting than translation initiation. While examining efp mutants, I discovered a novel phenotype of wild-type Salmonella. When dicarboxylates are the sole carbon source, Salmonella represses its growth using the general stress response sigma factor RpoS, the RpoS-stabilizer IraP, and repression of the dicarboxylate transporter DctA. Moreover, E. coli does not exhibit this phenotype and the E. coli dctA promoter is sufficient to induce Salmonella growth. This divergence suggests a potential role in virulence, and I examine the accumulation of succinate and itaconate in activated macrophage. I demonstrate that the dicarboxylate phenotype does not influence intracellular survival, and I propose novel hypotheses of why Salmonella has evolved this trait.
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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".