Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide.
Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide.
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作者：
Green J;Rolfe MD;Smith LJ
分子氧 (O2) 和一氧化氮 (NO) 是在感染中发挥重要作用的双原子气体。宿主先天免疫系统产生活性氧和一氧化氮作为杀菌剂，两者的产生都需要氧气。此外，适应氧气供应变化的能力对于许多细菌病原体来说至关重要，因为宿主内的许多生态位都是缺氧的。致病细菌已经进化出转录调节系统，可以感知这些气体并通过重新编程基因表达来做出反应。直接传感器具有含铁辅助因子（铁硫簇、单核铁、血红素）或与 O2 和/或 NO 反应的反应性半胱氨酸硫醇。间接传感器感知氧气不足的生理影响。因此，O2 和 NO 作为环境线索，触发宿主内生存所需的毒力基因的协调表达和代谢适应。在此，回顾了关键 O2 和 NO 反应细菌转录因子的信号感知机制以及对毒力基因表达的影响，然后考虑了两种主要病原体（金黄色葡萄球菌和结核分枝杆菌）中基因调控的这些方面。
Molecular oxygen (O2) and nitric oxide (NO) are diatomic gases that play major roles in infection. The host innate immune system generates reactive oxygen species and NO as bacteriocidal agents and both require O2 for their production. Furthermore, the ability to adapt to changes in O2 availability is crucial for many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic bacteria have evolved transcriptional regulatory systems that perceive these gases and respond by reprogramming gene expression. Direct sensors possess iron-containing co-factors (iron–sulfur clusters, mononuclear iron, heme) or reactive cysteine thiols that react with O2 and/or NO. Indirect sensors perceive the physiological effects of O2 starvation. Thus, O2 and NO act as environmental cues that trigger the coordinated expression of virulence genes and metabolic adaptations necessary for survival within a host. Here, the mechanisms of signal perception by key O2- and NO-responsive bacterial transcription factors and the effects on virulence gene expression are reviewed, followed by consideration of these aspects of gene regulation in two major pathogens, Staphylococcus aureus and Mycobacterium tuberculosis.