CpsA, a LytR-CpsA-Psr Family Protein in Mycobacterium marinum, Is Required for Cell Wall Integrity and Virulence
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Qinglan Wang1, Lin Zhu1, Victoria Jones2
1Key Laboratory of Medical Molecular Virology of MOE and MOH, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract:
LytR-CpsA-Psr family proteins play an important role in bacterial cell wall integrity. Although the pathogenic relevance of LytR-CpsA-Psr family proteins has been studied in a few bacterial pathogens, their function in mycobacteria remains uncharacterized. In this work, a transposon insertion mutant (cpsA::Tn) of Mycobacterium marinum was studied. We found that inactivation of CpsA altered bacterial colony morphology, sliding motility, cell surface hydrophobicity, and cell wall permeability. Besides, the cpsA mutant exhibited a decreased arabinogalactan content, indicating that CpsA plays a role in cell wall assembly. Moreover, the mutant shows impaired growth within macrophage cell lines and is severely attenuated in zebrafish larvae and adult zebrafish. Taken together, our results indicated that CpsA, a previously uncharacterized protein, is important for mycobacterial cell wall integrity and is required for mycobacterial virulence.
Insights
The study reveals that CpsA is crucial for maintaining mycobacterial cell wall integrity and virulence. Inactivation of this protein in Mycobacterium marinum impairs cell wall assembly and reduces pathogenicity.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Cell Wall Biology
Background:
- LytR-CpsA-Psr proteins are vital for bacterial cell wall integrity.
- Their role in mycobacteria, particularly Mycobacterium marinum, is largely unknown.
- Understanding these proteins is key to deciphering mycobacterial virulence.
Purpose of the Study:
- To investigate the function of CpsA in Mycobacterium marinum.
- To determine CpsA's role in cell wall assembly and integrity.
- To assess the impact of CpsA on mycobacterial virulence.
Main Methods:
- Construction and analysis of a transposon insertion mutant (cpsA::Tn) in Mycobacterium marinum.
- Assessment of cell wall properties including morphology, motility, hydrophobicity, and permeability.
- Quantification of arabinogalactan content.
- Evaluation of bacterial growth in macrophage cell lines and virulence in zebrafish models.
Main Results:
- Inactivation of CpsA significantly altered colony morphology, sliding motility, cell surface hydrophobicity, and cell wall permeability.
- The cpsA mutant showed reduced arabinogalactan content, indicating a role in cell wall assembly.
- The mutant exhibited impaired growth within macrophages and was severely attenuated in zebrafish larvae and adults.
Conclusions:
- CpsA is essential for maintaining mycobacterial cell wall integrity.
- CpsA plays a critical role in the virulence of Mycobacterium marinum.
- This study identifies CpsA as a novel virulence factor in mycobacteria.
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