Center for Infection and Immunity, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Zhuhai, China.
Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
Front Cell Infect Microbiol. 2021 Apr 13;11:629836. doi: 10.3389/fcimb.2021.629836. eCollection 2021.
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 gene in (), which reduced the resistance to acid medium. To further explore the function of PPE31, the mutant strain was generated in and (), respectively. Macrophages infected with the mutant strain caused a reduced inflammatory mediator expressions. In addition, macrophages infected with Δ had decreased host cell death dependent on JNK signaling. Consistent with these results, deletion of from increased the sensitivity to acid medium and reduced cell death in macrophages. Furthermore, we demonstrate that both mutants from and resulted in reduced survival in macrophages, and the survivability of was deceased in zebrafish due to loss of . Our findings confirm that PPE31 as a virulence associated factor that modulates innate immune responses to mycobacterial infection.
全基因组诱变鉴定出许多分枝杆菌感染和存活所必需的基因，但它们在宿主中的作用和作用机制还了解甚少。使用 CRISPR 干扰，我们在 () 中敲低了基因的表达，这降低了其对酸性介质的抗性。为了进一步探索 PPE31 的功能，分别在 () 和 () 中生成了 突变株。感染 突变株的巨噬细胞导致炎症介质表达减少。此外，感染 Δ 的巨噬细胞中依赖于 JNK 信号的宿主细胞死亡减少。与这些结果一致，从 中删除 增加了对酸性介质的敏感性，并减少了巨噬细胞中的细胞死亡。此外，我们证明了来自 和 的两种 突变株在巨噬细胞中的存活率降低，并且由于 的缺失，斑马鱼中的 的存活率降低。我们的研究结果证实，PPE31 是一种与毒力相关的因子，可调节分枝杆菌感染引起的固有免疫反应。
