Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Tuljaguda Complex, Nampally, Hyderabad, India.
Graduate Studies, Manipal University, Manipal, Karnataka, India.
Sci Rep. 2017 Jan 10;7:39706. doi: 10.1038/srep39706.
Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal. PPE2 was translocated into the macrophage nucleus via the classical importin α/β pathway where it interacted with a GATA-binding site overlapping with the TATA box of inos promoter and inhibited NO production. PPE2 prolonged intracellular survival of a surrogate bacterium M. smegmatis in vitro as well as in vivo. This information are likely to improve our knowledge of host-pathogen interactions during M. tuberculosis infection which is crucial for designing effective anti-TB therapeutics.
结核分枝杆菌是引起结核病的细菌，是人类最成功的病原体之一。它已经进化出几种适应技能和逃避机制，以劫持免疫教育过的宿主，使其适应细胞内的生活方式。在这里，我们表明，结核分枝杆菌的一种独特的 PPE 家族成员蛋白 PPE2 可以通过抑制 inos 基因转录来限制一氧化氮 (NO) 的产生。PPE2 蛋白具有亮氨酸拉链 DNA 结合基序和功能核定位信号。PPE2 通过经典的核输入蛋白 α/β 途径被转运到巨噬细胞核内，在那里它与 GATA 结合位点重叠，该位点与 inos 启动子的 TATA 盒重叠，并抑制 NO 的产生。PPE2 延长了替代细菌耻垢分枝杆菌在体外和体内的细胞内存活时间。这些信息可能会提高我们对结核分枝杆菌感染期间宿主-病原体相互作用的认识，这对于设计有效的抗结核治疗方法至关重要。
