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Thiol-based redox switches in prokaryotes

机译:原核生物中基于硫醇的氧化还原开关

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Bacteria encounter reactive oxygen species (ROS) as a consequence of the aerobic life or as an oxidative burst of activated neutrophils during infections. In addition, bacteria are exposed to other redox-active compounds, including hypochloric acid (HOCl) and reactive electrophilic species (RES) such as quinones and aldehydes. These reactive species often target the thiol groups of cysteines in proteins and lead to thiol-disulfide switches in redox-sensing regulators to activate specific detoxification pathways and to restore the redox balance. Here, we review bacterial thiol-based redox sensors that specifically sense ROS, RES and HOCl via thiol-based mechanisms and regulate gene transcription in Gram-positive model bacteria and in human pathogens, such as Staphylococcus aureus and Mycobacterium tuberculosis. We also pay particular attention to emerging widely conserved HOCl-specific redox regulators that have been recently characterized in Escherichia coli. Different mechanisms are used to sense and respond to ROS, RES and HOCl by 1-Cys-type and 2-Cys-type thiol-based redox sensors that include versatile thiol-disulfide switches (OxyR, OhrR, HypR, YodB, NemR, RclR, Spx, RsrA/RshA) or alternative Cys phosphorylations (SarZ, MgrA, SarA), thiol-S-alkylation (QsrR), His-oxidation (PerR) and methionine oxidation (HypT). In pathogenic bacteria, these redox-sensing regulators are often important virulence regulators and required for adapation to the host immune defense.
机译:由于有氧生活或感染过程中活化的中性粒细胞的氧化性爆发,细菌会遇到活性氧(ROS)。此外,细菌还暴露于其他氧化还原活性化合物,包括次氯酸(HOCl)和反应性亲电物种(RES),例如醌和醛。这些反应性物种通常以蛋白质中的半胱氨酸的巯基为目标,并导致氧化还原感应调节剂中的巯基-二硫键转换,以激活特定的排毒途径并恢复氧化还原平衡。在这里,我们回顾了基于细菌硫醇的氧化还原传感器,该传感器通过基于硫醇的机制专门检测ROS,RES和HOCl,并调节革兰氏阳性模型细菌和人类病原体(如金黄色葡萄球菌和结核分枝杆菌)中的基因转录。我们还特别注意最近在大肠杆菌中表征的新兴的,广泛保存的HOCl特异性氧化还原调节剂。通过1-Cys型和2-Cys型基于硫醇的氧化还原传感器使用不同的机制来感测ROS,RES和HOCl并对其做出响应,这些传感器包括通用的硫醇二硫键(OxyR,OhrR,HypR,YodB,NemR,RclR ,Spx,RsrA / RshA)或其他Cys磷酸化(SarZ,MgrA,SarA),硫醇S-烷基化(QsrR),His氧化(PerR)和蛋氨酸氧化(HypT)。在致病细菌中,这些氧化还原感应调节剂通常是重要的毒力调节剂,并且是适应宿主免疫防御的必需条件。

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