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Mycobacterium PPE31 Contributes to Host Cell Death
Siyuan Feng1,2, Zhongsi Hong1, Guoliang Zhang3
1Center for Infection and Immunity, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Zhuhai, China.
Frontiers in Cellular and Infection Microbiology
|April 30, 2021
Summary
The PPE31 gene is crucial for mycobacterial virulence and survival. Deleting it impairs infectivity and reduces inflammatory responses in host cells, impacting innate immunity.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Genome-wide mutagenesis reveals numerous genes essential for mycobacterial infectivity and survival.
- The precise roles and mechanisms of these genes within host environments remain largely uncharacterized.
Purpose of the Study:
- To investigate the function of the PPE31 gene in mycobacterial virulence.
- To elucidate PPE31's role in modulating host innate immune responses during infection.
Main Methods:
- CRISPR interference was used to create a knockdown of the PPE31 gene in Mycobacterium marinum.
- PPE31 mutant strains were generated in both Mycobacterium marinum and Mycobacterium tuberculosis.
- In vitro assays assessed acid resistance, macrophage inflammatory mediator expression, host cell death (JNK signaling), and intracellular survival.
- In vivo studies evaluated the survival of Mycobacterium marinum in zebrafish.
Main Results:
- Deletion of PPE31 reduced acid resistance in both M. marinum and M. tuberculosis.
- Macrophages infected with PPE31 mutants exhibited reduced inflammatory mediator expression and decreased JNK-dependent host cell death.
- PPE31 mutants showed significantly reduced survival within macrophages and decreased infectivity in a zebrafish model.
- Loss of PPE31 in M. tuberculosis increased sensitivity to acid stress.
Conclusions:
- PPE31 is a significant virulence-associated factor in mycobacteria.
- The PPE31 gene plays a critical role in modulating innate immune responses, contributing to mycobacterial survival and pathogenesis.
- Targeting PPE31 could be a potential strategy for controlling mycobacterial infections.
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