Mycobacterium tuberculosis WhiB3: a novel iron-sulfur cluster protein that regulates redox homeostasis and virulence.
Mycobacterium tuberculosis WhiB3: a novel iron-sulfur cluster protein that regulates redox homeostasis and virulence.
复制标题
DOI：
10.1089/ars.2011.4341
复制
发表时间：
2012-04
影响因子：
6.6
通讯作者：
V. Saini;Aisha Farhana;A. Steyn
中科院分区：
文献类型：
--
作者：
V. Saini;Aisha Farhana;A. Steyn
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是结核病（TB）的病原体，可在潜伏状态下持续数十年而不引起明显的疾病。由于潜伏性Mtb对目前的抗分枝杆菌药物是难治的，因此控制潜伏感染的进入、维持和出现的生物学机制的发现和表征对于开发新的临床疗法至关重要。最近的进展最近，Mtb WhiB 3，细胞内铁-硫（Fe-S）簇蛋白家族的成员已成为一个氧化还原传感器和效应分子控制Mtb毒力的几个方面。WhiB 3含有一个4Fe-4S簇，该簇特异性地与重要的宿主气体（O（2）和NO）以及外源和内源代谢信号反应以维持氧化还原平衡。值得注意的是，还原压力的概念来自于对WhiB 3的研究。关键问题WhiB 3如何作为细胞内氧化还原传感器发挥作用的详细机制尚不清楚。维持Mtb氧化还原平衡是特别重要的，因为杆菌在感染期间遇到大量的氧化还原应激源，并且因为几种抗分枝杆菌前药仅在分枝杆菌细胞质中的生物还原活化时有效。未来方向Mtb WhiB 3如何监测其内部和外部环境并调节内源性氧化还原途径，进而改变Mtb信号转导，核酸和蛋白质合成以及酶促活化，大多未被探索。现代表达，代谢组学和蛋白质组学技术应该为这些尚未回答的问题提供新的见解。
SIGNIFICANCE Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), can persist in a latent state for decades without causing overt disease. Since latent Mtb is refractory to current antimycobacterial drugs, the discovery and characterization of the biological mechanisms controlling the entry, maintenance, and emergence from latent infection is critical to the development of novel clinical therapies. RECENT ADVANCES Recently, Mtb WhiB3, a member of the family of intracellular iron-sulfur (Fe-S) cluster proteins has emerged as a redox sensor and effector molecule controlling several aspects of Mtb virulence. WhiB3 was shown to contain a 4Fe-4S cluster that specifically reacts with important host gases (O(2) and NO), and exogenous and endogenous metabolic signals to maintain redox balance. Notably, the concept of reductive stress emerged from studies on WhiB3. CRITICAL ISSUES The detailed mechanism of how WhiB3 functions as an intracellular redox sensor is unknown. Sustaining Mtb redox balance is particularly important since the bacilli encounter a large number of redox stressors during infection, and because several antimycobacterial prodrugs are effective only upon bioreductive activation in the mycobacterial cytoplasm. FUTURE DIRECTIONS How Mtb WhiB3 monitors its internal and external surroundings and modulates endogenous oxido-reductive pathways which in turn alter Mtb signal transduction, nucleic acid and protein synthesis, and enzymatic activation, is mostly unexplored. Modern expression, metabolomic and proteomic technologies should provide fresh insights into these yet unanswered questions.