Redox homeostasis in mycobacteria: the key to tuberculosis control?
Redox homeostasis in mycobacteria: the key to tuberculosis control?
复制标题
DOI：
10.1017/s1462399411002079
复制
发表时间：
2011-12-16
影响因子：
6.2
通讯作者：
Steyn AJ
中科院分区：
文献类型：
--
作者：
Kumar A;Farhana A;Guidry L;Saini V;Hondalus M;Steyn AJ
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是一种代谢灵活的病原体 它有非凡的能力去感知和适应不断变化的宿主 在几十年的持续感染中所经历的环境。曼恩商用车公司 持续暴露于内源性活性氧（ROS）作为正常有氧代谢的一部分， 呼吸，以及外源性ROS和活性氮物种（RNS）产生的 宿主免疫系统对感染作出反应。结核病的严重程度是 通过暴露于环境中的异生物质，如香烟烟雾， 和空气污染，导致细胞内 促氧化-抗氧化平衡氧化和还原应激均诱导 改变Mtb信号转导、DNA和RNA合成的氧化还原级联， 蛋白质合成和抗分枝杆菌药物抗性。如本文所述， 结核病已经进化出了特定的机制来保护自己免受 内源性产生的氧化剂，以及抵御宿主和环境氧化剂 以及在肺的微环境中发现的还原剂。维持 适当的氧化还原平衡对于临床结果是关键的， 抗分枝杆菌前药仅在生物还原活化时有效。适当 氧化还原系统的稳态对于Mtb存活是必需的， 持续存在并随后重新激活。进展和仍然存在的不足之处 理解结核分枝杆菌氧化还原稳态也进行了讨论。
Mycobacterium tuberculosis (Mtb) is a metabolically flexible pathogen that has the extraordinary ability to sense and adapt to the continuously changing host environment experienced during decades of persistent infection. Mtb is continually exposed to endogenous reactive oxygen species (ROS) as part of normal aerobic respiration, as well as exogenous ROS and reactive nitrogen species (RNS) generated by the host immune system in response to infection. The magnitude of tuberculosis (TB) disease is further amplified by exposure to xenobiotics from the environment such as cigarette smoke and air pollution, causing disruption of the intracellular prooxidant–antioxidant balance. Both oxidative and reductive stresses induce redox cascades that alter Mtb signal transduction, DNA and RNA synthesis, protein synthesis and antimycobacterial drug resistance. As reviewed in this article, Mtb has evolved specific mechanisms to protect itself against endogenously produced oxidants, as well as defend against host and environmental oxidants and reductants found specifically within the microenvironments of the lung. Maintaining an appropriate redox balance is critical to the clinical outcome because several antimycobacterial prodrugs are only effective upon bioreductive activation. Proper homeostasis of oxido-reductive systems is essential for Mtb survival, persistence and subsequent reactivation. The progress and remaining deficiencies in understanding Mtb redox homeostasis are also discussed.