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.

中文翻译：

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ATP合酶是结核分枝杆菌H37Ra中蛋白质酪氨酸磷酸酶调节生长和繁殖所必需的酶。

迄今为止，已知结核分枝杆菌（Mtb）蛋白酪氨酸磷酸酶（PtpA）可控制分枝杆菌的细胞内存活。然而，最近在开发突破性的抗结核药物二芳基喹啉中已考虑了分枝杆菌生长必不可少的ATP合酶。由于这两种酶均已被确定为经过验证的药物靶标，因此，我们通过使用Mtb H37Ra进行的一系列实验报告了这两种酶之间的稳固和功能关系。在本研究中，我们报告了分枝杆菌ATP合酶α亚基受PtpA调控。我们生成了酶PtpA的基因敲除，并测定了分枝杆菌复制和野生型，突变株（ΔptpA）和互补型（ΔptpA：ptpA）Mtb H37Ra菌株的蛋白质组谱。