PPE31 Contributes to Host Cell Death.

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.