Detoxification of toxins by bacillithiol in Staphylococcus aureus
Detoxification of toxins by bacillithiol in Staphylococcus aureus
复制标题
DOI：
10.1099/mic.0.055715-0
复制
发表时间：
2012-04-01
期刊：
影响因子：
2.8
通讯作者：
Rawat, Mamta
中科院分区：
文献类型：
--
作者：
Newton, Gerald L.;Fahey, Robert C.;Rawat, Mamta
芽孢杆菌硫醇（BSH），L-半胱氨酰-D-葡糖胺基-L-苹果酸的α-端基糖苷，是在细菌如芽孢杆菌属中发现的主要低分子量硫醇，金黄色葡萄球菌和耐辐射球菌。与其他低分子量硫醇（如谷胱甘肽和真菌硫醇）一样，BSH可能参与保护环境毒素，包括硫醇反应性抗生素。我们在这里报告了一个BSH依赖的解毒机制在S。金黄色。当S.金黄色葡萄球菌纽曼菌株用一溴二氢吡喃和一氯二氢吡喃处理后，细胞内的BSH转化为荧光S-共轭物BS-二氢吡喃。芽孢杆菌硫醇缀合物酰胺酶活性作用于BS-二亚胺以产生Cys-二亚胺，其然后通过N-乙酰转移酶乙酰化以产生N-乙酰基-Cys-二亚胺，一种巯基尿酸。色葡萄缺乏BSH的金黄色葡萄球菌突变体在用monobromobimane和monochlorobimane处理时不产生巯基尿酸，证实了杆菌硫醇的参与。此外，S.金黄色葡萄球菌纽曼与利福霉素（一线抗结核药物利福平的母体化合物）的比较表明，由于在培养基中观察到利福霉素的巯基尿酸，因此这种硫醇反应性抗生素也以FSH依赖性方式解毒。这些数据表明，毒素和巯基反应性抗生素是以一种BSH依赖的方式解毒为效力较低的巯基尿酸，然后在S.金黄色。
Bacillithiol (BSH), an alpha-anomeric glycoside of L-cysteinyl-D-glucosaminyl-L-malate, is a major low-molecular-mass thiol found in bacteria such as Bacillus sp., Staphylococcus aureus and Deinococcus radiodurans. Like other low-molecular-mass thiols such as glutathione and mycothiol, BSH is likely to be involved in protection against environmental toxins including thiol-reactive antibiotics. We report here a BSH-dependent detoxification mechanism in S. aureus. When S. aureus Newman strain was treated with monobromobimane and monochlorobimane, the cellular BSH was converted to the fluorescent S-conjugate BS-bimane. A bacillithiol conjugate amidase activity acted upon the BS-bimane to produce Cys-bimane, which was then acetylated by an N-acetyltransferase to generate N-acetyl-Cys-bimane, a mercapturic acid. An S. aureus mutant lacking BSH did not produce mercapturic acid when treated with monobromobimane and monochlorobimane, confirming the involvement of bacillithiol. Furthermore, treatment of S. aureus Newman with rifamycin, the parent compound of the first-line anti-tuberculosis drug, rifampicin, indicated that this thiol-reactive antibiotic is also detoxified in a BSH-dependent manner, since mercapturic acids of rifamycin were observed in the culture medium. These data indicate that toxins and thiol-reactive antibiotics are detoxified to less potent mercapturic acids in a BSH-dependent manner and then exported out of the cell in S. aureus.