From the Department of Molecular, Cellular, and Developmental Biology.
From the Department of Molecular, Cellular, and Developmental Biology; the Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan 48109.
J Biol Chem. 2013 Nov 8;288(45):32574-32584. doi: 10.1074/jbc.M113.503516. Epub 2013 Sep 27.
Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.
活性氯物质(RCS)如次氯酸是一种强大的抗菌氧化剂。RCS 广泛用于家庭和工业环境的消毒(即作为漂白剂),也在先天免疫反应中大量自然产生。细菌对 RCS 的反应是复杂的,与对其他生理相关氧化剂(如过氧化物或超氧化物)的特征反应有很大的不同。已经在细菌中鉴定出几种 RCS 敏感的转录因子,但它们大多数都对多种应激源做出反应,这些应激源的破坏作用与 RCS 的破坏作用重叠,包括活性氧物质和亲电物。我们现在使用体内遗传和体外生化方法来鉴定和证明大肠杆菌 RclR(以前称为 YkgD)是 AraC 家族的一种氧化还原调节转录激活因子,其高度保守的半胱氨酸残基对 RCS 的氧化特别敏感。这些半胱氨酸的氧化导致对 RCS 应激所需的生存相关基因的强烈、高度特异性的表达激活。这些结果表明存在一个广泛保守的细菌调节子,专门用于 RCS 抗性。