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Updated: May 20, 2026
Modeling Tuberculosis in Mycobacterium marinum Infected Adult Zebrafish
Published on: October 8, 2018
Mycobacterium marinum SecA2 promotes stable granulomas and induces tumor necrosis factor alpha in vivo
Brigitte Y Watkins1, Shilpa A Joshi, David A Ball
1Department of Microbial Pathogenesis, Genentech, Inc., South San Francisco, California, USA.
Abstract:
SecA2 is an ATPase present in some pathogenic Gram-positive bacteria, is required for translocation of a limited set of proteins across the cytosolic membrane, and plays an important role in virulence in several bacteria, including mycobacteria that cause diseases such as tuberculosis and leprosy. However, the mechanisms by which SecA2 affects virulence are incompletely understood. To investigate whether SecA2 modulates host immune responses in vivo, we studied Mycobacterium marinum infection in two different hosts: an established zebrafish model and a recently described mouse model. Here we show that M. marinum ΔsecA2 was attenuated for virulence in both host species and SecA2 was needed for normal granuloma numbers and for optimal tumor necrosis factor alpha response in both zebrafish and mice. M. marinum ΔsecA2 was more sensitive to SDS and had unique protrusions from its cell envelope when examined by cryo-electron tomography, suggesting that SecA2 is important for bacterial cell wall integrity. These results provide evidence that SecA2 induces granulomas and is required for bacterial modulation of the host response because it affects the mycobacterial cell envelope.
Insights
SecA2 protein is crucial for virulence in pathogenic bacteria like Mycobacterium marinum. Its absence weakens bacteria and impacts host immune responses, highlighting SecA2
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- SecA2 is an ATPase in pathogenic Gram-positive bacteria, essential for protein translocation and virulence.
- Its precise role in modulating host immune responses, particularly in mycobacteria causing tuberculosis and leprosy, remains unclear.
Purpose of the Study:
- To investigate the role of SecA2 in modulating host immune responses in vivo.
- To explore the impact of SecA2 on Mycobacterium marinum virulence in zebrafish and mouse models.
Main Methods:
- Studied Mycobacterium marinum infection in zebrafish and mouse models.
- Utilized cryo-electron tomography to examine bacterial cell envelope structure.
- Assessed bacterial virulence, granuloma formation, and host tumor necrosis factor alpha response.
Main Results:
- Mycobacterium marinum lacking SecA2 (M. marinum ΔsecA2) showed reduced virulence in both zebrafish and mice.
- SecA2 was essential for normal granuloma numbers and optimal tumor necrosis factor alpha response.
- M. marinum ΔsecA2 exhibited increased sensitivity to SDS and unique cell envelope protrusions, indicating compromised cell wall integrity.
Conclusions:
- SecA2 plays a significant role in M. marinum virulence by influencing granuloma formation and host immune modulation.
- SecA2 is critical for maintaining mycobacterial cell envelope integrity.
- These findings suggest SecA2 affects the host response by altering the bacterial cell envelope.
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