Abstract：
The PE and PPE family proteins of Mycobacterium tuberculosis (Mtb) is exclusively found in pathogenic Mycobacterium species, comprising approximately 8-10 % of the Mtb genome. These emerging virulent factors have been observed to play pivotal roles in Mtb pathogenesis and immune evasion through various strategies. These immunogenic proteins are known to modulate the host immune response and cell-death pathways by targeting the powerhouse of the cell, the mitochondria to support Mtb survival. In this article, we are focused on how PE/PPE family proteins target host mitochondria to induce mitochondrial perturbations, modulate the levels of cellular ROS (Reactive oxygen species) and control cell death pathways. We observed that the time of expression of these proteins at different stages of infection is crucial for elucidating their impact on the cell death pathways and eventually on the outcome of infection. This article focuses on understanding the contributions of the PE/PPE proteins by unravelling the triad of host mitochondria, oxidative stress and cell death pathways that facilitate the Mtb persistence. Understanding the role of these proteins in host cellular pathways and the intricate mechanisms paves the way for the development of novel therapeutic strategies to combat TB infections.
摘要：
结核分枝杆菌（Mtb）的PE和PPE家族蛋白仅在致病性分枝杆菌物种中发现，包含大约8-10%的Mtb基因组。已观察到这些新兴的毒力因子通过各种策略在Mtb发病机理和免疫逃避中起关键作用。已知这些免疫原性蛋白通过靶向细胞的动力室来调节宿主免疫应答和细胞死亡途径。支持Mtb存活的线粒体。在这篇文章中,我们专注于PE/PPE家族蛋白如何靶向宿主线粒体以诱导线粒体扰动，调节细胞ROS（活性氧）的水平并控制细胞死亡途径。我们观察到，这些蛋白质在感染不同阶段的表达时间对于阐明它们对细胞死亡途径和最终感染结果的影响至关重要。本文主要通过解开宿主线粒体的三联体来理解PE/PPE蛋白的贡献，促进Mtb持久性的氧化应激和细胞死亡途径。了解这些蛋白质在宿主细胞途径中的作用和复杂的机制为开发新型治疗策略以对抗TB感染铺平了道路。
