Screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model

Dalton, J. P., Uy, B., Okuda, K. S., Hall, C. J., Denny, W. A., Crosier, P. S., Swift, S. and Wiles, S. (2017) Screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model. Journal of Antimicrobial Chemotherapy, 72 2: 421-427. doi:10.1093/jac/dkw421


Author Dalton, J. P.
Uy, B.
Okuda, K. S.
Hall, C. J.
Denny, W. A.
Crosier, P. S.
Swift, S.
Wiles, S.
Title Screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2017-01-01
Sub-type Article (original research)
DOI 10.1093/jac/dkw421
Open Access Status DOI
Volume 72
Issue 2
Start page 421
End page 427
Total pages 7
Place of publication Birmingham, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Objectives: Mycobacterium tuberculosis is a deadly human pathogen that causes the lung disease TB.
M. tuberculosis latently infects a third of the world’s population, resulting in 1.5 million deaths per year. Due
to the difficulties and expense of carrying out animal drug trials using M. tuberculosis and rodents, infections
of the zebrafish Danio rerio with Mycobacterium marinum have become a useful surrogate. However, the infection
methods described to date require specialized equipment and a high level of operator expertise.
Methods: We investigated whether zebrafish larvae could be naturally infected with bioluminescently labelled
M. marinum by immersion, and whether infected larvae could be used for rapid screening of anti-mycobacterial
compounds using bioluminescence. We used rifampicin and a variety of nitroimidazole-based next-generation
and experimental anti-mycobacterial drugs, selected for their wide range of potencies against M. tuberculosis, to
validate this model for anti-mycobacterial drug discovery.
Results: We observed that five of the six treatments (rifampicin, pretomanid, delamanid, SN30488 and SN30527)
significantly reduced the bioluminescent signal from M. marinum within naturally infected zebrafish larvae.
Importantly, these same five treatments also retarded the growth of M. tuberculosis in vitro. In contrast, only
three of the six treatments tested (rifampicin, delamanid and SN30527) retarded the growth of M. marinum
in vitro.
Conclusions: We have demonstrated that zebrafish larvae naturally infected with bioluminescent M. marinum M
can be used for the rapid screening of anti-mycobacterial compounds with readily available equipment and
limited expertise. The result is an assay that can be carried out by a wide variety of laboratories for minimal
cost and without high levels of zebrafish expertise.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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