Freie Universität Berlin, Institute for Biology-Microbiology, Königin-Luise-Strasse 12-16, D-14195 Berlin, Germany.
Freie Universität Berlin, Laboratory of Structural Biochemistry, D-14195 Berlin, Germany; Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz 90-924, Poland.
Redox Biol. 2019 Jan;20:130-145. doi: 10.1016/j.redox.2018.08.017. Epub 2018 Aug 24.
Low molecular weight (LMW) thiols play an important role as thiol-cofactors for many enzymes and are crucial to maintain the reduced state of the cytoplasm. Most Gram-negative bacteria utilize glutathione (GSH) as major LMW thiol. However, in Gram-positive Actinomycetes and Firmicutes alternative LMW thiols, such as mycothiol (MSH) and bacillithiol (BSH) play related roles as GSH surrogates, respectively. Under conditions of hypochlorite stress, MSH and BSH are known to form mixed disulfides with protein thiols, termed as S-mycothiolation or S-bacillithiolation that function in thiol-protection and redox regulation. Protein S-thiolations are widespread redox-modifications discovered in different Gram-positive bacteria, such as Bacillus and Staphylococcus species, Mycobacterium smegmatis, Corynebacterium glutamicum and Corynebacterium diphtheriae. S-thiolated proteins are mainly involved in cellular metabolism, protein translation, redox regulation and antioxidant functions with some conserved targets across bacteria. The reduction of protein S-mycothiolations and S-bacillithiolations requires glutaredoxin-related mycoredoxin and bacilliredoxin pathways to regenerate protein functions. In this review, we present an overview of the functions of mycothiol and bacillithiol and their physiological roles in protein S-bacillithiolations and S-mycothiolations in Gram-positive bacteria. Significant progress has been made to characterize the role of protein S-thiolation in redox-regulation and thiol protection of main metabolic and antioxidant enzymes. However, the physiological roles of the pathways for regeneration are only beginning to emerge as well as their interactions with other cellular redox systems. Future studies should be also directed to explore the roles of protein S-thiolations and their redox pathways in pathogenic bacteria under infection conditions to discover new drug targets and treatment options against multiple antibiotic resistant bacteria.
低分子量（LMW）巯基化合物作为许多酶的巯基辅因子发挥着重要作用，对于维持细胞质的还原状态至关重要。大多数革兰氏阴性菌利用谷胱甘肽（GSH）作为主要的 LMW 巯基化合物。然而，在革兰氏阳性放线菌和厚壁菌门中，替代的 LMW 巯基化合物，如麦硫因（MSH）和芽孢硫醇（BSH）分别作为 GSH 的替代物发挥相关作用。在次氯酸盐应激条件下，MSH 和 BSH 已知与蛋白质巯基形成混合二硫键，称为 S-麦硫因化或 S-芽孢硫醇化，这些反应在巯基保护和氧化还原调节中发挥作用。蛋白质 S-巯基化是在不同革兰氏阳性菌中发现的广泛的氧化还原修饰，如芽孢杆菌和葡萄球菌属、耻垢分枝杆菌、谷氨酸棒杆菌和白喉棒杆菌。S-巯基化蛋白主要参与细胞代谢、蛋白质翻译、氧化还原调节和抗氧化功能，在不同细菌中有一些保守的靶标。蛋白质 S-麦硫因化和 S-芽孢硫醇化的还原需要依赖谷胱甘肽相关的麦硫因还原酶和芽孢硫醇还原酶途径来恢复蛋白质的功能。在这篇综述中，我们概述了麦硫因和芽孢硫醇的功能及其在革兰氏阳性菌中蛋白质 S-芽孢硫醇化和 S-麦硫因化的生理作用。在氧化还原调节和主要代谢和抗氧化酶的巯基保护方面，对蛋白质 S-巯基化的作用已经取得了显著的进展。然而，这些途径在蛋白质再生方面的生理作用才刚刚开始显现，并且它们与其他细胞氧化还原系统的相互作用也在不断发展。未来的研究还应致力于探索感染条件下蛋白质 S-巯基化及其氧化还原途径在病原菌中的作用，以发现针对多药耐药菌的新药物靶点和治疗方法。
