PUBLICATION
Optimization and validation of Mycobacterium marinum-induced adult zebrafish model for evaluation of oral anti-tuberculosis drugs
- Authors
- Sridevi, J.P., Anantaraju, H.S., Kulkarni, P., Yogeeswari, P., Sriram, D.
- ID
- ZDB-PUB-160121-8
- Date
- 2014
- Source
- International journal of mycobacteriology 3: 259-67 (Journal)
- Registered Authors
- Kulkarni, Pushkar
- Keywords
- Adult zebrafish, Anti-tuberculosis drugs, Drug discovery, Mycobacterium marinum, Mycobacterium tuberculosis, Oral dosing
- MeSH Terms
- none
- PubMed
- 26786625 Full text @ Int J Mycobacteriol
Citation
Sridevi, J.P., Anantaraju, H.S., Kulkarni, P., Yogeeswari, P., Sriram, D. (2014) Optimization and validation of Mycobacterium marinum-induced adult zebrafish model for evaluation of oral anti-tuberculosis drugs. International journal of mycobacteriology. 3:259-67.
Abstract
Introduction Mycobacterium marinum has emerged as a suitable species for induction of tuberculosis-like disease in zebrafish, and various zebrafish models (larval and adult) for drug screening have been proposed in the literature. It is believed that an adult zebrafish model is more useful in drug screening because, apart from assessment of efficacy, one can obtain data on dosage, pharmacokinetics and overall health improvement. This study suggests a simple, cost-effective and resource-efficient protocol for screening of anti-tuberculosis drugs.
Methods The parameters used for assessment of infection as well as anti-bacterial response were: (a) bacterial count; and (b) body weight change. An optimization study was conducted to establish the concentration of bacteria required to produce a reproducible phenotype of tuberculosis (TB). A negative control (Amoxicillin) and anti-mycobacterial drugs (Isoniazid, Rifampicin, Moxifloxacin, Ethambutol and Isoniazid+Rifampicin) were used for validation of the protocol. All the drugs were administered orally.
Results An intra-peritoneal inoculation of 0.75million bacteria/fish was optimized for the model. All the anti-tuberculosis drugs showed efficacy in this model, whereas the negative control did not show any signs of reversing the parameters of M. marinum infection.
Discussion Adult zebrafish model of M. marinum-induced tuberculosis has not been fully exploited as a drug screening tool. In the present report, a protocol is suggested that is simple, reproducible and resource-efficient for screening of anti-tuberculosis agents. This protocol is an attempt to refine the published protocols and use this model as a surrogate model of human TB for the purpose of drug screening.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping