Control of Copper Resistance and Inorganic Sulfur Metabolism by Paralogous Regulators in Staphylococcus aureus
Control of Copper Resistance and Inorganic Sulfur Metabolism by Paralogous Regulators in Staphylococcus aureus
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DOI：
10.1074/jbc.m111.220012
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发表时间：
2011-04-15
影响因子：
4.8
通讯作者：
Giedroc, David P.
中科院分区：
文献类型：
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作者：
Grossoehme, Nicholas;Kehl-Fie, Thomas E.;Giedroc, David P.
所有金黄色葡萄球菌菌株都编码一种假定的铜敏感操纵子阻遏物（CsoR）以及另一种功能未知的类CsoR蛋白。我们在此表明，NWMN_1991编码金黄色葡萄球菌纽曼菌株中一个基因上不相连的copA - copZ铜抗性操纵子的一种真正的Cu（I）诱导型CsoR。相比之下，在NWMN_0027和NWMN_0026之间发现的一个未注释的开放阅读框（标记为NWMN_0026.5）编码一种类CsoR调节因子，它通过特异性结合位于NWMN_0027 - 0026.5基因间区域的一对典型操纵位点来抑制相邻基因的表达。对这些受调控基因的研究表明，它们在从硫代硫酸盐同化无机硫以及定向硫转移中起作用，我们将NWMN_0026.5命名为CstR（类CsoR硫转移酶阻遏物）。表达分析表明，CsoR和CstR响应不同的刺激来控制它们各自的调控子，在体内没有重叠。与CsoR不同，CstR不会与Cu（I）形成稳定的复合物；相反，操纵子结合会因亚基间半胱氨酸对被硫代硫酸盐同化的一种可能代谢产物亚硫酸盐氧化为二硫键和三硫键的混合物而受到抑制。在相同条件下，CsoR对亚硫酸盐没有反应。我们得出结论，CsoR和CstR是金黄色葡萄球菌中的旁系同源物，它们在同一细胞质中发挥作用以控制不同的生理过程。
All strains of Staphylococcus aureus encode a putative copper-sensitive operon repressor (CsoR) and one other CsoR-like protein of unknown function. We show here that NWMN_1991 encodes a bona fide Cu(I)-inducible CsoR of a genetically unlinked copA-copZ copper resistance operon in S. aureus strain Newman. In contrast, an unannotated open reading frame found between NWMN_0027 and NWMN_0026 (denoted NWMN_0026.5) encodes a CsoR-like regulator that represses expression of adjacent genes by binding specifically to a pair of canonical operator sites positioned in the NWMN_0027-0026.5 intergenic region. Inspection of these regulated genes suggests a role in assimilation of inorganic sulfur from thiosulfate and vectorial sulfur transfer, and we designate NWMN_0026.5 as CstR (CsoR-like sulfur transferase repressor). Expression analysis demonstrates that CsoR and CstR control their respective regulons in response to distinct stimuli with no overlap in vivo. Unlike CsoR, CstR does not form a stable complex with Cu(I); operator binding is instead inhibited by oxidation of the intersubunit cysteine pair to a mixture of disulfide and trisulfide linkages by a likely metabolite of thiosulfate assimilation, sulfite. CsoR is unreactive toward sulfite under the same conditions. We conclude that CsoR and CstR are paralogs in S. aureus that function in the same cytoplasm to control distinct physiological processes.