ArticleDisease models & mechanisms2021
An anti-tuberculosis compound screen using a zebrafish infection model identifies an aspartyl-tRNA synthetase inhibitor.
Article in Disease models & mechanisms, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Zebrafish swimming towards cures: a scalable NAM platform for drug discovery.Drug discovery today · 2026Review
- Review
- Single and Combined Effects of Meropenem, Valproic Acid, and Ketoprofen on Adult Zebrafish Behavior, Oxidative Stress, and Acetylcholinesterase Activity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Impact of Animal Models and Strain Standardization on the Evaluation of Tuberculosis Vaccine Efficacy.Vaccines · 2025Review
- Modulating mycobacterial envelope integrity for antibiotic synergy with benzothiazoles.Life science alliance · 2024Article
- Vitamin BMicrobiology spectrum · 2024Article
- Diving into drug-screening: zebrafish embryos as an in vivo platform for antimicrobial drug discovery and assessment.FEMS microbiology reviews · 2024Review
- The tunicamycin derivative TunR2 exhibits potent antibiotic properties with low toxicity in an in vivo Mycobacterium marinum-zebrafish TB infection model.The Journal of antibiotics · 2024Article
- Study on the Anti-Marine drugs · 2024Article
- Article
- Dysregulation ofBiomolecules · 2023Article
- Modelling infectious disease to support human health.Disease models & mechanisms · 2022Article
- New therapeutic strategies forExpert review of anti-infective therapyReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Finding new anti-tuberculosis compounds with convincing in vivo activity is an ongoing global challenge to fight the emergence of multidrug-resistant Mycobacterium tuberculosis isolates. In this study, we exploited the medium-throughput capabilities of the zebrafish embryo infection model with Mycobacterium marinum as a surrogate for M. tuberculosis. Using a representative set of clinically established drugs, we demonstrate that this model could be predictive and selective for antibiotics that can be administered orally. We further used the zebrafish infection model to screen 240 compounds from an anti-tuberculosis hit library for their in vivo activity and identified 14 highly active compounds. One of the most active compounds was the tetracyclic compound TBA161, which was studied in more detail. Analysis of resistant mutants revealed point mutations in aspS (rv2572c), encoding an aspartyl-tRNA synthetase. The target was genetically confirmed, and molecular docking studies propose the possible binding of TBA161 in a pocket adjacent to the catalytic site. This study shows that the zebrafish infection model is suitable for rapidly identifying promising scaffolds with in vivo activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.