Laboratory of Biotechnology, Chulabhorn Research Institute, Lak Si, Bangkok, Thailand.
J Bacteriol. 2012 Oct;194(20):5495-503. doi: 10.1128/JB.00304-12. Epub 2012 Jul 13.
The ability to maintain intracellular concentrations of toxic reactive oxygen species (ROS) within safe limits is essential for all aerobic life forms. In bacteria, as well as other organisms, ROS are produced during the normal course of aerobic metabolism, necessitating the constitutive expression of ROS scavenging systems. However, bacteria can also experience transient high-level exposure to ROS derived either from external sources, such as the host defense response, or as a secondary effect of other seemingly unrelated environmental stresses. Consequently, transcriptional regulators have evolved to sense the levels of ROS and coordinate the appropriate oxidative stress response. Three well-studied examples of these are the peroxide responsive regulators OxyR, PerR, and OhrR. OxyR and PerR are sensors of primarily H(2)O(2), while OhrR senses organic peroxide (ROOH) and sodium hypochlorite (NaOCl). OxyR and OhrR sense oxidants by means of the reversible oxidation of specific cysteine residues. In contrast, PerR senses H(2)O(2) via the Fe-catalyzed oxidation of histidine residues. These transcription regulators also influence complex biological phenomena, such as biofilm formation, the evasion of host immune responses, and antibiotic resistance via the direct regulation of specific proteins.
维持细胞内有毒活性氧 (ROS) 浓度在安全范围内的能力对所有需氧生命形式都是必不可少的。在细菌以及其他生物中,ROS 是在有氧代谢的正常过程中产生的,这就需要持续表达 ROS 清除系统。然而,细菌也会经历短暂的高水平 ROS 暴露,这些 ROS 要么来自外部来源,如宿主防御反应,要么是其他看似无关的环境压力的次级效应。因此,转录调节因子已经进化到能够感知 ROS 的水平,并协调适当的氧化应激反应。这方面有三个研究得比较透彻的例子,即过氧化物响应调节因子 OxyR、PerR 和 OhrR。OxyR 和 PerR 主要感知 H(2)O(2),而 OhrR 则感知有机过氧化物 (ROOH) 和次氯酸钠 (NaOCl)。OxyR 和 OhrR 通过特定半胱氨酸残基的可逆氧化来感知氧化剂。相比之下,PerR 通过组氨酸残基的 Fe 催化氧化来感知 H(2)O(2)。这些转录调节因子还通过直接调节特定蛋白质来影响生物膜形成、逃避宿主免疫反应和抗生素耐药性等复杂的生物学现象。