The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus.

The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus.
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DOI:
10.1111/mmi.12835
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发表时间:
2014-12
影响因子:
3.6
通讯作者:
Giedroc DP
Giedroc DP
中科院分区:
生物学2区
文献类型:
--
作者:
Luebke JL;Shen J;Bruce KE;Kehl-Fie TE;Peng H;Skaar EP;Giedroc DP

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细胞如何调节可利用硫的生物利用度,同时减轻硫化氢毒性的影响尚不清楚。CstR(铜感应操纵子抑制因子(CsoR)样硫转移酶抑制因子)抑制金黄色葡萄球菌中编码硫化物氧化系统的cst操纵子的表达。在这里,我们表明,在细胞硫化物胁迫的急性期和特异性反应中,cst操纵子被强烈和短暂地诱导,并且cst编码基因对于减轻硫化物毒性的影响是必要的。当金黄色葡萄球菌在以硫代硫酸盐(TS)作为唯一硫源的化学定义培养基中培养时,生长缺陷最为明显,但当使用胱氨酸或在富培养基中培养时也很明显。在TS生长条件下,由于ΔcstR菌株中不受调节的cst操纵子表达或用不可诱导的C31A/C60A CstR转化而阻断cst诱导,细胞无法生长。这表明成本操纵子有助于细胞硫稳态。串联高分辨率质谱分析显示,CstR被无机四硫化物和有机过硫化物谷胱甘肽过硫化物衍生,生成Cys31-Cys60 '原聚体间交联的混合物,包括二、三和四硫化物键,这些键变构性地抑制CstR与cst操作符DNA的结合。
How cells regulate the bioavailability of utilizable sulfur while mitigating the effects of hydrogen sulfide toxicity is poorly understood. CstR (Copper-sensing operon repressor (CsoR)-like sulfurtransferase repressor) represses the expression of the cst operon encoding a putative sulfide oxidation system in Staphylococcus aureus. Here, we show that the cst operon is strongly and transiently induced by cellular sulfide stress in an acute phase and specific response and that cst-encoded genes are necessary to mitigate the effects of sulfide toxicity. Growth defects are most pronounced when S. aureus is cultured in chemically defined media with thiosulfate (TS) as a sole sulfur source, but are also apparent when cystine is used or in rich media. Under TS growth conditions, cells fail to grow as a result of either unregulated expression of the cst operon in a ΔcstR strain or transformation with a non-inducible C31A/C60A CstR that blocks cst induction. This suggests that the cst operon contributes to cellular sulfide homeostasis. Tandem high resolution mass spectrometry reveals derivatization of CstR by both inorganic tetrasulfide and an organic persulfide, glutathione persulfide, to yield a mixture of Cys31-Cys60’ interprotomer crosslinks, including di-, tri- and tetrasulfide bonds, which allosterically inhibit cst operator DNA binding by CstR.
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