CtsR controls class III heat shock gene expression in the human pathogen Listeria monocytogenes
CtsR controls class III heat shock gene expression in the human pathogen Listeria monocytogenes
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DOI：
10.1046/j.1365-2958.2000.01752.x
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发表时间：
2000-02-01
影响因子：
3.6
通讯作者：
Berche, P
中科院分区：
文献类型：
--
作者：
Nair, S;Derré, I;Berche, P
应激蛋白在病原菌的毒力中起着重要作用，但对病原菌应激反应的调控知之甚少。在兼性细胞内病原体单核细胞增生李斯特菌中，Clp ATP酶（包括ClpC、ClpP和ClpE）是应激存活和细胞内生长所必需的。clpC操纵子的第一个基因是L.单核细胞增多症编码应激反应基因的枯草芽孢杆菌CtsR阻遏物的同源物。安湖单核细胞增多症ctsR缺失突变体在应激条件下（在2%NaCl存在下或在42 ° C下生长）表现出增强的存活，但其在小鼠中的毒力水平不受影响。组成型表达CtsR的野生型菌株的毒力显著减弱，推测是因为应激反应的抑制。L的规则。使用B中的转录融合研究单核细胞增生症clpC、clpP和clpE基因。subtilis作为宿主。洛杉矶将单核细胞增多症ctsR基因置于诱导型启动子的控制下，并且在B中体内证实了通过CtsR和热休克的调节。枯草芽孢杆菌纯化的L.单核细胞增多症特异性结合clpC、clpP和clpE调节区，并且CtsR结合位点的程度由DNA酶I足迹法确定。我们的研究结果表明，这种人类病原体具有一个CtsR调节子控制III类热休克基因，惊人的相似，saplete B。枯草杆菌。这是第一次描述病原体中的应激反应调控基因。
Stress proteins play an important role in virulence, yet little is known about the regulation of stress response in pathogens. In the facultative intracellular pathogen Listeria monocytogenes, the Clp ATPases, including ClpC, ClpP and ClpE, are required for stress survival and intracellular growth. The first gene of the clpC operon of L. monocytogenes encodes a homologue of the Bacillus subtilis CtsR repressor of stress response genes. An L. monocytogenes ctsR-deleted mutant displayed enhanced survival under stress conditions (growth in the presence of 2% NaCl or at 42 degrees C), but its level of virulence in the mouse was not affected. The virulence of a wild-type strain constitutively expressing CtsR is significantly attenuated, presumably because of repression of the stress response. Regulation of the L. monocytogenes clpC, clpP and clpE genes was investigated using transcriptional fusions in B. subtilis as a host. The L. monocytogenes ctsR gene was placed under the control of an inducible promoter, and regulation by CtsR and heat shock was demonstrated in vivo in B. subtilis. The purified CtsR protein of L. monocytogenes binds specifically to the clpC, clpP and clpE regulatory regions, and the extent of the CtsR binding sites was defined by DNase I footprinting. Our results demonstrate that this human pathogen possesses a CtsR regulon controlling class III heat shock genes, strikingly similar to that of the saprophyte B. subtilis. This is the first description of a stress response regulatory gene in a pathogen.