Mycobacterium marinum SecA2 Promotes Stable Granulomas and Induces Tumor Necrosis Factor Alpha In Vivo
- Authors
- Watkins, B.Y., Joshi, S.A., Ball, D.A., Leggett, H., Park, S., Kim, J., Austin, C.D., Paler-Martinez, A., Xu, M., Downing, K.H., and Brown, E.J.
- ID
- ZDB-PUB-120807-25
- Date
- 2012
- Source
- Infection and Immunity 80(10): 3512-3520 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adenosine Triphosphatases/genetics
- Adenosine Triphosphatases/metabolism*
- Animals
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism*
- Cells, Cultured
- Female
- Granuloma/microbiology*
- Humans
- Inflammation/metabolism
- Macrophages
- Membrane Transport Proteins/genetics
- Membrane Transport Proteins/metabolism*
- Mice
- Mice, Inbred C57BL
- Mycobacterium Infections, Nontuberculous/immunology
- Mycobacterium Infections, Nontuberculous/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology*
- Mycobacterium marinum/genetics
- Mycobacterium marinum/metabolism*
- Mycobacterium marinum/pathogenicity
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Necrosis Factor-alpha/genetics
- Tumor Necrosis Factor-alpha/metabolism*
- Virulence
- Zebrafish
- PubMed
- 22851747 Full text @ Infect. Immun.
SecA2 is an ATPase present in some pathogenic Gram-positive bacteria, which 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 like 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 TNF-α 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.