PROTEASOMAL REGULATION AND PROTEIN QUALITY CONTROL IN M. TUBERCULOSIS

全球每年有近200万人死于结核病。多年来，我们已经确定 结核分枝杆菌(Mtb)蛋白酶体是结核杆菌在动物体内存活所必需的。 蛋白酶体是以高度调控的方式降解蛋白质的多亚基、桶形蛋白酶。 我们目前正在研究蛋白质分解是如何被调控的，从蛋白质是如何被唯一已知的 细菌蛋白质对蛋白质的翻译后修饰，以确定这些标记的蛋白质然后如何输送到 蛋白酶体核心蛋白酶。其次，这项建议将寻求了解一个必不可少的功能 受蛋白酶体降解调节的蛋白质质量控制系统。确定该系统如何 对结核分枝杆菌生理学的贡献可能会确定抗击结核病感染的新方法。因此，这些研究将 揭示蛋白酶体如何感知细胞外信号，以优化致命感染所需的细菌生长。

Tuberculosis kills nearly 2 million people globally every year. Over the years, we have determined that the Mycobacterium tuberculosis (Mtb) proteasome is essential to allow the tubercle bacilli to persist in animals. Proteasomes are multi-subunit, barrel shaped proteases that degrade proteins in a highly regulated manner. We are currently examining how proteolysis is regulated, from how proteins are tagged with the only known bacterial protein-on-protein post-translational modification to how those tagged proteins are then delivered into the proteasome core protease. Secondly, this proposal will seek to understand the functions of an essential protein quality control system that is regulated by proteasomal degradation. Identifying how this system contributes to Mtb physiology may identify new ways to combat tuberculosis infections. Thus, these studies will reveal how a proteasome senses extracellular signals to optimize bacterial growth required for lethal infections.