Curtin Medical School, Faculty of Health Sciences, Curtin University, Bentley, Perth, WA 6102, Australia.
Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Perth, WA 6102, Australia.
Int J Mol Sci. 2024 Nov 20;25(22):12481. doi: 10.3390/ijms252212481.
() is a remarkably versatile pathogen that possesses a unique ability to counteract the host's defence mechanisms to control the infection. Several mycobacterial protein kinases and phosphatases were found to play a key role in impeding phagosome maturation in macrophages and accordingly blocking the phagosome-lysosome fusion, therefore allowing the bacteria to survive. During phagocytosis, both and the host's phagocytic cells develop mechanisms to fight each other, resulting in pathogen elimination or survival. In this respect, uses a phosphorylation-based signal transduction mechanism, whereby it senses extracellular signals from the host and initiates the appropriate adaptation responses. Indeed, the ability of to exist in different states in the host (persistent quiescent state or actively replicating mode) is mainly mediated through protein phosphorylation/dephosphorylation signalling. The regulatory and defensive responses coordinate different aspects of the bacilli's physiology, for instance, cell wall components, metabolic activity, virulence, and growth. Herein, we will discuss the implication of kinases and phosphatases in hijacking the host immune system, perpetuating the infection. In addition, the role of PknG, MPtpA, MPtpB, and SapM inhibitors in resetting the host immune system will be highlighted.
结核分枝杆菌是一种非常灵活的病原体，具有独特的能力来对抗宿主的防御机制以控制感染。已经发现几种分枝杆菌蛋白激酶和磷酸酶在阻碍巨噬细胞中的吞噬体成熟以及相应地阻止吞噬体-溶酶体融合方面发挥关键作用，从而使细菌得以存活。在吞噬作用过程中，结核分枝杆菌和宿主的吞噬细胞都发展出相互对抗的机制，导致病原体被消除或存活。在这方面，结核分枝杆菌利用基于磷酸化的信号转导机制，感知来自宿主的细胞外信号，并启动适当的适应反应。实际上，结核分枝杆菌在宿主中存在不同状态（持续静止状态或主动复制模式）的能力主要是通过蛋白磷酸化/去磷酸化信号转导来介导的。结核分枝杆菌的调节和防御反应协调了杆菌生理学的不同方面，例如细胞壁成分、代谢活性、毒力和生长。在此，我们将讨论结核分枝杆菌激酶和磷酸酶在劫持宿主免疫系统、使感染持续存在方面的作用。此外，还将强调 PknG、MPtpA、MPtpB 和 SapM 抑制剂在重置宿主免疫系统方面的作用。
