Division of Microbiology and Academy of Scientific and Innovative Research(+), CSIR-Central Drug Research Institute, Lucknow, 226031, India.
Division of Microbiology and Academy of Scientific and Innovative Research(+), CSIR-Central Drug Research Institute, Lucknow, 226031, India.
Biochimie. 2019 Oct;165:156-160. doi: 10.1016/j.biochi.2019.07.023. Epub 2019 Aug 1.
Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase (PtpA) has so far been known to control intracellular survival of mycobacteria; whereas the ATP synthase which is essential for mycobacterial growth has recently been contemplated in developing a breakthrough anti-TB drug, diarylquinoline. Since both of these enzymes have been established as validated drug targets; we report a robust and functional relationship between these two enzymes through a series of experiments using Mtb H37Ra. In the present study we report that the mycobacterial ATP synthase alpha subunit is regulated by PtpA. We generated gene knock-out for the enzyme PtpA and subjected to determine the mycobacterial replication and the proteome profile of wild type, mutant (ΔptpA) and complemented (ΔptpA:ptpA) strains of Mtb H37Ra. A substantial amount of decrease in the protein level of ATP synthase alpha subunit (AtpA) in case of mutant H37Ra was observed, while the levels of the enzyme were either increased or remained unchanged, in wild type and in the complemented strains.
结核分枝杆菌（Mtb）蛋白酪氨酸磷酸酶（PtpA）迄今已知可控制分枝杆菌的细胞内存活；而 ATP 合酶对于分枝杆菌的生长至关重要，最近被考虑用于开发一种突破性的抗结核药物，二芳基喹啉。由于这两种酶都已被确立为有效的药物靶点；我们通过一系列使用 Mtb H37Ra 的实验报告了这两种酶之间的稳健而功能上的关系。在本研究中，我们报告了分枝杆菌 ATP 合酶α亚基受 PtpA 调节。我们生成了该酶 PtpA 的基因敲除体，并对野生型、突变型（ΔptpA）和互补型（ΔptpA：ptpA）的 Mtb H37Ra 菌株的分枝杆菌复制和蛋白质组谱进行了测定。在突变体 H37Ra 中，观察到 ATP 合酶α亚基（AtpA）的蛋白水平大量下降，而在野生型和互补型菌株中，该酶的水平要么增加，要么保持不变。
