Calcium is a very important second messenger, whose concentration in various cellular compartments is under tight regulation. A disturbance in the levels of calcium in these compartments can play havoc in the cell, as it regulates various cellular processes by direct or indirect mechanisms. Here, we have investigated the functional importance of a calcium transporting P2A ATPase, CtpF of Mycobacterium tuberculosis (Mtb) in the pathogen's interaction with the host. Among its uncanny ways of dealing with the host with umpteen strategies for survival and persistence in humans, CtpF is identified as a new player. The levels of ctpF are upregulated in macrophage stresses like hypoxia, high nitric oxide levels and acidic pH. Using confocal microscopy and fluorimetry, we show that CtpF effluxes calcium in macrophages in early stages of Mtb infection. Downregulation of ctpF expression by conditional knockdown resulted in perturbation of host calcium levels and consequent decreased activation of mTOR. We present a mechanism how calcium efflux by the pathogen inhibits mTOR-dependent autophagy and enhances bacterial survival. Our work highlights how Mtb engages its metal efflux pumps to exploit host autophagic process for its proliferation.

钙是非常重要的第二信使，钙在各种细胞室中的浓度受到严格的调节。这些隔室中钙水平的紊乱会在细胞中造成破坏，因为它通过直接或间接机制调节各种细胞过程。在这里，我们研究了钙转运P2A ATPase，CtpF的功能重要性。结核分枝杆菌（mtb）中病原体与宿主的相互作用。CtpF是其以多种生存和持久性策略与宿主打交道的怪异方式，被认为是新的参与者。的水平ctpF在缺氧，高一氧化氮水平和酸性pH的巨噬细胞应激中被上调。使用共聚焦显微镜和荧光法，我们显示CtpF在Mtb感染的早期阶段流出了巨噬细胞中的钙。下调ctpF通过条件性敲低的表达导致宿主钙水平的扰动，并因此降低了mTOR的活化。我们提出了一种机制，病原体的钙外排如何抑制mTOR依赖性自噬并增强细菌存活率。我们的工作重点介绍了Mtb如何利用其金属外排泵来利用宿主自噬过程使其增殖。