σ32-Mediated negative regulation of Salmonella pathogenicity island 1 expression
σ32-Mediated negative regulation of Salmonella pathogenicity island 1 expression
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DOI：
10.1128/jb.00744-08
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发表时间：
2008-10-01
影响因子：
3.2
通讯作者：
Yamamoto, Tomoko
中科院分区：
文献类型：
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作者：
Matsui, Mari;Takaya, Akiko;Yamamoto, Tomoko
沙门氏菌致病岛1（SPI1）能够感染沙门氏菌侵入肠上皮细胞，并诱导促炎反应和巨噬细胞死亡。SPI1的表达是由一个复杂的级联反应控制的几个转录调控因子内的岛屿和全球监管机构外it.Previously，我们报告说，DnaK耗尽鲑鱼既不能侵入上皮细胞，也不能分泌SPI1编码的蛋白，这表明DnaK参与了SPI1的表达。在这里，我们发现DnaK通过抑制sigma（32）蛋白参与SPI 1的表达，该蛋白指导一组基因的转录以响应各种全局应力。sigma（32）的过量产生导致SPI1特异性转录调节因子HilD和HilA的水平降低。进一步的分析表明sigma（32）介导的系统分别在翻译后和转录水平负调控HilD和HilA。这种负调节的执行者被证明是sigma（32）诱导的蛋白ATP依赖性Lon蛋白酶，其特异性降解HilD。由于HilD可以激活hilA的转录，是在顶部的分级SPI 1调节环，并具有主导作用，HilD的翻译后控制的Lon是至关重要的精确表达的SPI 1。因此，我们认为SPI1的表达是由反馈调节环控制的，其中sigma（32）诱导Lon控制HilD和DnaK的周转，DnaK抑制sigma（32）功能，导致Lon表达的调节。这种对环境信号的特定组合的调节将确保SPI1表达被限制在宿主中的几个特定位置。
Salmonella pathogenicity island 1 (SPI1) enables infecting salmonellae to invade the intestinal epithelium and induce a proinflammatory response and macrophage cell death. SPI1 expression is controlled by a complex cascade with several transcriptional regulators within the island and global regulators outside it. Previously, we reported that DnaK-depleted salmonellae could neither invade epithelial cells nor secrete SPI1-encoded proteins, suggesting that DnaK is involved in the expression of SPI1. Here, we found that DnaK is involved in SPI1 expression through inhibition of sigma(32) protein, which directs the transcription of a group of genes in response to various global stresses. Overproduction of sigma(32) resulted in decreased levels of the SPI1-specific transcriptional regulators HilD and HilA. Further analysis demonstrated that the sigma(32)-mediated system negatively regulates HilD and HilA at the posttranslational and transcriptional levels, respectively. The executioner of this negative regulation was shown to be a sigma(32)-induced protein ATP-dependent Lon protease, which specifically degrades HilD. Since HilD can activate hilA transcription, is at the top of the hierarchical SPI1 regulatory loop, and has a dominant role, the posttranslational control of HilD by Lon is critically important for precise expression of SPI1. Consequently, we suggest that SPI1 expression is controlled by the feedback regulatory loop in which sigma(32) induces Lon to control turnover of HilD, and DnaK, which inhibits sigma(32) function, leading to the modulation of lon expression. This regulation in response to a specific combination of environmental signals would ensure that SPI1 expression is restricted to a few specific locations in the host.