Related Experiment Video
Updated: Apr 27, 2026
Modeling Tuberculosis in Mycobacterium marinum Infected Adult Zebrafish
Published on: October 8, 2018
Modeling tuberculous meningitis in zebrafish using Mycobacterium marinum
Lisanne M van Leeuwen1, Martijn van der Kuip2, Sameh A Youssef3
1Department of Pediatric Infectious Diseases and Immunology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands Department of Medical Microbiology and Infection Control, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
Researchers adapted a zebrafish model to study tuberculous meningitis (TBM). The model successfully demonstrated granuloma formation in the brain, offering new insights into TBM pathogenesis and potential therapeutic targets.
Area of Science:
- Neuroscience
- Infectious Diseases
- Zebrafish Models
Background:
- Tuberculous meningitis (TBM) is a severe form of tuberculosis with high mortality.
- Rich foci, brain-specific granulomas, are characteristic of TBM, but their early role remains unclear.
- Understanding TBM early pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To adapt and validate the zebrafish model for studying tuberculous meningitis (TBM).
- To investigate the early pathogenesis of TBM, focusing on granuloma formation and bacterial dissemination in the brain.
- To explore the role of Rich foci in TBM development using a novel model system.
Main Methods:
- Adapted the zebrafish-Mycobacterium marinum infection model for TBM research.
- Infected adult zebrafish and embryos via various routes (intraperitoneal, parenchyma, hindbrain ventricle, caudal vein).
- Analyzed granuloma formation, bacterial infiltration, and blood-brain barrier (BBB) integrity in infected zebrafish.
Main Results:
- TBM-like granulomas formed in the meninges and brain parenchyma of adult zebrafish.
- Zebrafish embryos showed efficient bacterial infiltration and early granuloma formation in brain tissue, irrespective of BBB development.
- An M. marinum ESX-1 mutant showed impaired granuloma formation in the zebrafish brain.
Conclusions:
- The adapted zebrafish-M. marinum model is suitable for studying TBM pathogenesis.
- The model allows for detailed analysis of bacterial and host factors in TBM.
- This research may lead to improved diagnostic tools and therapeutics for TBM.
