PUBLICATION
The zebrafish embryo as an in vivo model for screening nanoparticle-formulated lipophilic anti-tuberculosis compounds
- Authors
- Dal, N.K., Speth, M., Johann, K., Barz, M., Beauvineau, C., Wohlmann, J., Fenaroli, F., Gicquel, B., Griffiths, G., Alonso-Rodriguez, N.
- ID
- ZDB-PUB-211130-7
- Date
- 2021
- Source
- Disease models & mechanisms 15(1): (Journal)
- Registered Authors
- Keywords
- Anti-tuberculosis drugs, Nanoparticles, Zebrafish tuberculosis model, in vivo efficacy, in vivo toxicity
- MeSH Terms
-
- Animals
- Antitubercular Agents/pharmacology
- Antitubercular Agents/therapeutic use
- Mice
- Mycobacterium tuberculosis*
- Nanoparticles*
- Tuberculosis*/drug therapy
- Tuberculosis*/microbiology
- Zebrafish/microbiology
- PubMed
- 34842273 Full text @ Dis. Model. Mech.
Citation
Dal, N.K., Speth, M., Johann, K., Barz, M., Beauvineau, C., Wohlmann, J., Fenaroli, F., Gicquel, B., Griffiths, G., Alonso-Rodriguez, N. (2021) The zebrafish embryo as an in vivo model for screening nanoparticle-formulated lipophilic anti-tuberculosis compounds. Disease models & mechanisms. 15(1):.
Abstract
With the increasing emergence of drug-resistant Mycobacterium tuberculosis strains, new and effective antibiotics against tuberculosis (TB) are urgently needed. However, the high frequency of poorly water-soluble compounds among hits in high-throughput drug screening (HTS) campaigns is a major obstacle in drug discovery. Moreover, in vivo testing using conventional animal TB models such as mice is time-consuming and costly, and represents a major bottleneck in lead compound discovery and development. Here, we report the use of the zebrafish embryo TB model, to evaluate the in vivo toxicity and efficacy of five poorly water-soluble nitronaphthofuran derivatives, which were recently identified to possess anti-tuberculosis activity in vitro. To aid solubilization compounds were formulated in biocompatible polymeric micelles (PM). Three of the five PM-formulated nitronaphthofuran derivatives showed low toxicity in vivo, significantly reduced bacterial burden and improved survival in infected zebrafish embryos. We propose the zebrafish embryo TB-model as a quick and sensitive tool for evaluating in vivo toxicity and efficacy of new anti-TB compounds during early stages of drug development. Thus, this model is well suited to pinpoint promising compounds for further development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping