Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.629836
Keywords
virulence factors; PPE31; cell death; Mycobacterium tuberculosis; JNK signaling
Categories
Funding
- National Science and Technology Key Projects for Major Infectious Diseases [2017ZX10302301002]
- National Natural Science Foundation of China [31470877]
- Development Project of Foshan Fourth People's Hospital [FSSYKF-2020003, FSSYKF-2020017]
- Guangzhou Science and Technology Planning Project [201704020226, 201604020006]
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CRISPR interference was used to study the ppe31 gene in Mycobacterium marinum and Mycobacterium tuberculosis, revealing its role in resistance to acid medium, inflammatory mediator expression in infected macrophages, and host cell death. Deletion of ppe31 from both strains increased sensitivity to acid medium and decreased cell death in macrophages, indicating PPE31 as a virulence factor modulating innate immune responses to mycobacterial infection.
Genome scale mutagenesis identifies many genes required for mycobacterial infectivity and survival, but their contributions and mechanisms of action within the host are poorly understood. Using CRISPR interference, we created a knockdown of ppe31(Mm) gene in Mycobacterium marinum (M. marinum), which reduced the resistance to acid medium. To further explore the function of PPE31, the ppe31 mutant strain was generated in M. marinum and Mycobacterium tuberculosis (M. tuberculosis), respectively. Macrophages infected with the ppe31(Mm) mutant strain caused a reduced inflammatory mediator expressions. In addition, macrophages infected with M. marinum Delta ppe31(Mm) had decreased host cell death dependent on JNK signaling. Consistent with these results, deletion of ppe31(Mtb) from M. tuberculosis increased the sensitivity to acid medium and reduced cell death in macrophages. Furthermore, we demonstrate that both ppe31 mutants from M. marinum and M. tuberculosis resulted in reduced survival in macrophages, and the survivability of M. marinum was deceased in zebrafish due to loss of ppe31(Mm) . Our findings confirm that PPE31 as a virulence associated factor that modulates innate immune responses to mycobacterial infection.
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