School of Chemistry and Molecular Biosciences, Australian Infectious Disease Research Centre, University of Queensland, Brisbane, Queensland, Australia.
Mol Microbiol. 2022 May;117(5):973-985. doi: 10.1111/mmi.14899. Epub 2022 Apr 11.
Intracellular bacterial pathogens such as Mycobacterium tuberculosis are remarkably adept at surviving within a host, employing a variety of mechanisms to counteract host defenses and establish a protected niche. Constant surveying of the environment is key for pathogenic mycobacteria to discern their immediate location and coordinate the expression of genes necessary for adaptation. Two-component systems efficiently perform this role, typically comprised of a transmembrane sensor kinase and a cytoplasmic response regulator. In this review, we describe the role of two-component systems in bacterial pathogenesis, focusing predominantly on the role of sensor kinases of M. tuberculosis. We highlight important features of sensor kinases in mycobacterial infection, discuss ways in which these signaling proteins sense and respond to environments, and how this is attuned to their intracellular lifestyle. Finally, we discuss recent studies which have identified and characterized inhibitors of two-component sensor kinases toward establishing a new strategy in anti-mycobacterial therapy.
细胞内细菌病原体，如结核分枝杆菌，在宿主内生存的能力非常强，它们利用多种机制来对抗宿主防御并建立一个受保护的小生境。不断监测环境对于致病性分枝杆菌来说是关键，以便识别它们的位置并协调适应所需基因的表达。双组分系统能够有效地完成这一角色，通常由跨膜传感器激酶和细胞质响应调节剂组成。在这篇综述中，我们描述了双组分系统在细菌发病机制中的作用，主要集中在结核分枝杆菌传感器激酶的作用上。我们强调了传感器激酶在分枝杆菌感染中的重要特征，讨论了这些信号蛋白如何感知和响应环境，以及如何适应其细胞内生活方式。最后，我们讨论了最近的研究，这些研究已经确定并描述了双组分传感器激酶的抑制剂，为抗分枝杆菌治疗建立了一种新的策略。
