The bactericidal FabI inhibitor Debio 1453 clears antibiotic-resistant Neisseria gonorrhoeae infection in vivo
Bibliographic record
Abstract
Gonorrhoea is a prevalent sexually transmitted infection caused by the bacterial pathogen Neisseria gonorrhoeae. N. gonorrhoeae has demonstrated a remarkable capacity to evolve antibiotic resistance, with emerging strains that show resistance to all standard treatment options. The development of new antibiotics for gonorrhoea, especially those with novel targets and no pre-existing resistance, is critical. One such untapped antibacterial target in N. gonorrhoeae is FabI, an enoyl-acyl carrier protein reductase enzyme that is essential for fatty acid biosynthesis in this pathogen. In the current report, structure-based drug design using novel N. gonorrhoeae FabI inhibitor co-crystals guides medicinal chemistry toward increasing potency in the sub-nanomolar range and drives the discovery of Debio 1453. Debio 1453 is optimized for activity against N. gonorrhoeae and is highly active in vitro against diverse N. gonorrhoeae isolates including those resistant to the last remaining treatment options. Additionally, the compound presents a low propensity for selection of mutants with reduced susceptibility. Debio 1453 is efficacious in vivo against N. gonorrhoeae isolates with clinically relevant multi-drug resistance phenotypes in a murine vaginal gonorrhoea infection model underscoring Debio 1453 as a promising candidate for the treatment of gonorrhoea.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".