Mycobacterium is known for subverting the host defense machinery, and one such mechanism is the inhibition of autophagy. Here, we have demonstrated that Mycobacterium tuberculosis (MTB) secretes a virulence factor; an early secretory antigenic target protein (ESAT-6) into the phagosome, which induces the expression and activity of mitochondrial superoxide dismutase (SOD-2) of macrophages. Using a series of experiments, and Mycobacterium bovis BCG as a model strain (where ESAT-6 protein is not expressed), we have delineated that the protein regulates SOD-2 of macrophages. The expression and augmentation of SOD-2 activity were confirmed by either incubating the macrophages with ESAT-6 protein, transfection of macrophage by esat6 gene using a eukaryotic promoter vector, or by infection with different mycobacterial strains. The induction of acidification of phagosomal compartment containing bacteria was observed in cells that express low levels of SOD-2. This was further confirmed by observing a significant decrease in the M. bovis BCG intracellular load in the sod-2 knocked-down macrophages.

分枝杆菌以破坏宿主防御机制而闻名，其中一种机制是抑制自噬。在这里，我们证明了结核分枝杆菌（MTB）会分泌一种毒力因子。吞噬体中的一种早期分泌性抗原靶蛋白（ESAT-6），可诱导巨噬细胞线粒体超氧化物歧化酶（SOD-2）的表达和活性。使用一系列实验，并将牛分枝杆菌BCG作为模型菌株（其中ESAT-6蛋白未表达），我们已经确定该蛋白调节巨噬细胞的SOD-2。通过将巨噬细胞与ESAT-6蛋白一起孵育，通过esat6转染巨噬细胞来确认SOD-2活性的表达和增强。使用真核启动子载体或通过感染不同的分枝杆菌菌株来获得该基因。在表达低水平SOD-2的细胞中观察到了吞噬细胞隔室细菌的酸化诱导。通过观察在sod-2敲低的巨噬细胞中牛分枝杆菌BCG细胞内负荷的显着降低，进一步证实了这一点。