Targeting the Thioredoxin Reductase–Thioredoxin System from Staphylococcus aureus by Silver Ions,Inorganic Chemistry

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Targeting the Thioredoxin Reductase–Thioredoxin System from Staphylococcus aureus by Silver Ions
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2017-11-28 00:00:00 , DOI: 10.1021/acs.inorgchem.7b01904
Xiangwen Liao _{1,

2} , Fang Yang ₁ , Hongyan Li ₃ , Pui-Kin So ₄ , Zhongping Yao ₄ , Wei Xia ₁ , Hongzhe Sun _{1,

3}

Affiliation

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 ions 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 μM and 15.0 ± 5.0 μM 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.

中文翻译：

银离子靶向金黄色葡萄球菌硫氧还蛋白还原酶-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）组成的硫氧还蛋白系统是细菌用来抵抗氧化应激的主要二硫化物还原酶系统之一。特别是，这种还原酶系统对于缺乏天然谷胱甘肽/谷胱甘肽（Grx）系统的致病性金黄色葡萄球菌至关重要。尽管银离子和含银材料已被用作抗菌剂已有数百年历史，但人们对银的抗菌机理还不甚了解。在此，我们证明银离子以1.4±0.1μM和15.0±5.0μM的解离常数以及1和2 Ag ^+的化学计量比结合金黄色葡萄球菌TrxR和Trx的活性位点每个蛋白质离子。重要的是，银离子结合导致TrxR和Trx的低聚和功能破坏。银还耗尽了金黄色葡萄球菌的细胞内硫醇水平，破坏了细菌硫醇-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系统可能是抗菌药物设计的可行目标。

更新日期：2017-11-28

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