Targeting the Thioredoxin Reductase-Thioredoxin System from Staphylococcus aureus by Silver Ions
Targeting the Thioredoxin Reductase-Thioredoxin System from Staphylococcus aureus by Silver Ions
复制标题
通过银离子靶向金黄色葡萄球菌的硫氧还蛋白还原酶 - 硫氧还蛋白系统
DOI：
10.1021/acs.inorgchem.7b01904
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发表时间：
2017-12-18
影响因子：
4.6
通讯作者：
Sun, Hongzhe
中科院分区：
文献类型：
--
作者：
Liao, Xiangwen;Yang, Fang;Sun, Hongzhe
硫氧还蛋白系统由NADPH、硫氧还蛋白还原酶（TrxR）和硫氧还蛋白（Trx）组成，是细菌抵抗氧化应激的主要二硫还原酶系统之一。特别是，这种还原酶系统对于致病性细菌金黄色葡萄球菌的生存至关重要，金黄色葡萄球菌缺乏天然的谷胱甘肽/谷氧还蛋白（Grx）系统。虽然银和含银的材料已经被用作抗菌剂几个世纪，但银的抗菌机制还没有被很好地理解。在此，我们证明了银离子结合到S的活性位点。金黄色葡萄球菌TrxR和Trx的解离常数分别为1.4 +/- 0.1 μ M和15.0 +/- 5.0 μ M，每个蛋白质的化学计量分别为1和2个Ag+离子。重要的是，银离子结合导致TrxR以及Trx的寡聚化和功能破坏。银也耗尽S.金黄色葡萄球菌，破坏细菌巯基氧化还原稳态。我们的研究为银离子的抗菌机理提供了新的见解。此外，Trx和TrxR系统可能作为一个可行的目标，抗菌药物的设计。
The thioredoxin system, which is composed of NADPH, thioredoxin reductase (TrxR), and thioredoxin (Trx), is one of the major disulfide reductase systems used by bacteria against oxidative stress. In particular, this reductase system is crucial for the survival of the pathogenic bacterium Staphylococcus aureus, which lacks a natural glutathione/glutaredoxin (Grx) system. Although silver Rills and silver containing materials have been used as antibacterial agents for centuries, the antibacterial mechanism of silver is not well understood. Herein, we demonstrate that silver ions bind to the active sites of S. aureus TrxR and Trx with dissociation constants of 1.4 +/- 0.1 mu M and 15.0 +/- 5.0 mu M and stoichiometries of 1 and 2 Ag+ ions per protein, respectively. Importantly, silver ion binding leads to oligomerization and functional disruption of TrxR as well as Trx. Silver also depleted intracellular thiol levels in S. aureus, disrupting bacterial thiol-redox homeostasis. Our study provides new insights into the antibacterial mechanism of silver ions. Moreover, the Trx and TrxR system might serve as a feasible target for the design of antibacterial drugs.