Coordinated regulation of expression of Salmonella pathogenicity island 1 and flagellar type III secretion systems by ATP-dependent ClpXP protease
Coordinated regulation of expression of Salmonella pathogenicity island 1 and flagellar type III secretion systems by ATP-dependent ClpXP protease
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DOI：
10.1128/jb.01385-07
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发表时间：
2008-04-01
影响因子：
3.2
通讯作者：
Yamamoto, Tomoko
中科院分区：
文献类型：
--
作者：
Kage, Hirokazu;Takaya, Akiko;Yamamoto, Tomoko
鼠伤寒沙门氏菌通过沙门氏菌致病岛1（SPI1）编码的III型分泌系统将多种蛋白质递送到宿主细胞中，在那里它们引起几种生理变化，包括细菌入侵、巨噬细胞凋亡和肠道致病。一旦沙门氏菌建立了全身性感染，过量的巨噬细胞凋亡将对病原体有害，因为它利用巨噬细胞作为载体在整个宿主中全身传播。因此，SPI1的表达必须限于宿主中的一个或几个特定位置。在本研究中，我们已经证明，这种复合物的基因的表达被抑制的ATP依赖性ClpXP蛋白酶，因此抑制巨噬细胞凋亡。ClpXP的耗竭导致两种SPI1编码的转录调节因子HilC和HilD的量显著增加，从而刺激hilA诱导，从而激活SPI1表达。我们的证据表明，ClpXP通过控制鞭毛基因表达来调节HilC和HilD的细胞水平。随后的实验表明，鞭毛相关的基因产物FliZ控制HilD转录后，这反过来激活HilC。这些发现表明ClpXP蛋白酶共调节SPI1相关的毒力表型和运动性。ClpXP是在暴露于不利环境（如巨噬细胞）的细菌中诱导的应激蛋白家族的成员。
Salmonella enterica serovar Typhimurium delivers a variety of proteins via the Salmonella pathogenicity island 1 (SPI1)-encoded type III secretion system into host cells, where they elicit several physiological changes, including bacterial invasion, macrophage apoptosis, and enteropathogenesis. Once Salmonella has established a systemic infection, excess macrophage apoptosis would be detrimental to the pathogen, as it utilizes macrophages as vectors for systemic dissemination throughout the host. Therefore, SPI1 expression must be restricted to one or a few specific locations in the host. In the present study, we have demonstrated that the expression of this complex of genes is repressed by the ATP-dependent ClpXP protease, which therefore suppresses macrophage apoptosis. Depletion of ClpXP caused significant increases in the amounts of two SPI1-encoded transcriptional regulators, HilC and HilD, leading to the stimulation of hilA induction and therefore activation of SPI1 expression. Our evidence shows that ClpXP regulates cellular levels of HilC and HilD via the control of flagellar gene expression. Subsequent experiments demonstrated that the flagellum-related gene product FliZ controls HilD posttranscriptionally, and this in turn activates HilC. These findings suggest that the ClpXP protease coregulates SPI1-related virulence phenotypes and motility. ClpXP is a member of the stress protein family induced in bacteria exposed to hostile environments such as macrophages.