Efficacy of epetraborole against <i>Mycobacterium abscessus</i> is increased with norvaline
Bibliographic record
Abstract
Abstract Certain aminoacyl-tRNA synthetases developed a proofreading mechanism to ensure aminoacylation of tRNAs with cognate amino acids. Epetraborole (EPT) was identified as an inhibitor of the leucyl-tRNA synthetase (LeuRS) editing site in Mycobacterium abscessus . EPT displayed enhanced activity against M. abscessus over Mycobacterium tuberculosis . Crystallographic and equilibrium binding data showed that EPT binds LeuRS Mabs and LeuRS Mtb with similar Kd. Proteomic analysis revealed that when M. abscessus LeuRS mutants were fed the non-proteinogenic amino acid norvaline, leucine residues in proteins were replaced by norvaline, inducing expression of GroEL chaperonins and Clp proteases. In vitro data revealed that supplementation of media with norvaline reduced the emergence of EPT mutants in both M. abscessus and M. tuberculosis . The combination of EPT and norvaline had improved in vivo efficacy compared to EPT in a murine model of M. abscessus infection.
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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".