Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis
Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis
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DOI：
10.1073/pnas.1603192113
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发表时间：
2016-10-11
影响因子：
11.1
通讯作者：
Soncini, Fernando C.
中科院分区：
文献类型：
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作者：
Pezza, Alejandro;Pontel, Lucas B.;Soncini, Fernando C.
（铜稳态对于细菌病原体适应性和感染至关重要，并且一直是最近许多研究的焦点。在沙门氏菌中，针对铜超载的包膜保护和巨噬细胞的生存取决于 CueP，它是周质中的主要铜结合蛋白。该蛋白还需要将金属离子传递到 Cu/Zn 超氧化物歧化酶 SodCII。沙门氏菌特异性 CueP 编码基因最初被鉴定为 Cue 调节子的一部分，受 Cue 调节子的转录控制。细胞质铜传感器 CueR，但其表达与其他 CueR 调节基因不同。在这里，我们表明，cueP 表达受 CueR 和 CpxR/CpxA 的协同作用控制，CueR 检测细胞质中铜的存在，而 CpxR/CpxA 监测包膜应力。铜激活的 CueR 对于 cueP 启动子的 -10 和 -35 元件的适当空间排列是必需的，而 CpxR 对于招募 RNA 聚合酶至关重要。两个祖先感觉系统——CueR（提供信号特异性）和 CpxR/CpxA（检测细菌包膜中的应激）——将这种周质铜抗性蛋白的表达仅限于遇到过量铜（扰乱包膜稳态）的细胞，模拟其他肠道细菌中存在的 CusR/CusS 调节系统的作用。
( Copper homeostasis is essential for bacterial pathogen fitness and infection, and has been the focus of a number of recent studies. In Salmonella, envelope protection against copper overload and macrophage survival depends on CueP, a major copper-binding protein in the periplasm. This protein is also required to deliver the metal ion to the Cu/Zn superoxide dismutase SodCII. The Salmonella-specific CueP-coding gene was originally identified as part of the Cue regulon under the transcriptional control of the cytoplasmic copper sensor CueR, but its expression differs from the rest of CueR-regulated genes. Here we show that cueP expression is controlled by the concerted action of CueR, which detects the presence of copper in the cytoplasm, and by CpxR/CpxA, which monitors envelope stress. Copper-activated CueR is necessary for the appropriate spatial arrangement of the -10 and -35 elements of the cueP promoter, and CpxR is essential to recruit the RNA polymerase. The integration of two ancestral sensory systems-CueR, which provides signal specificity, and CpxR/CpxA, which detects stress in the bacterial envelope-restricts the expression of this periplasmic copper resistance protein solely to cells encountering surplus copper that disturbs envelope homeostasis, emulating the role of the CusR/CusS regulatory system present in other enteric bacteria.