FliZ Regulates Expression of the Salmonella Pathogenicity Island 1 Invasion Locus by Controlling HilD Protein Activity in Salmonella enterica Serovar Typhimurium
FliZ Regulates Expression of the Salmonella Pathogenicity Island 1 Invasion Locus by Controlling HilD Protein Activity in Salmonella enterica Serovar Typhimurium
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DOI：
10.1128/jb.00635-10
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发表时间：
2010-12-01
影响因子：
3.2
通讯作者：
Slauch, James M.
中科院分区：
文献类型：
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作者：
Chubiz, Jessica E. Cott;Golubeva, Yekaterina A.;Slauch, James M.
肠道沙门氏菌引起肠道和全系统疾病的先决条件是通过3型分泌系统（T3SS）将效应蛋白直接注射到宿主肠上皮细胞中；沙门氏菌致病性岛1 （SPI1）携带T3SS基因。这些效应蛋白诱导炎症性腹泻和细菌侵袭。SPI1 T3SS的表达受到各种全球调控系统的严格调控，以响应环境信号。我们之前已经证明，三种类似arac的调节因子HilD、HilC和RtsA在一个复杂的前馈调节回路中起作用，控制hilA基因的表达，hilA基因编码SPI1结构基因的直接调节因子。在这项工作中，我们描述了这个系统的一个主要的正调节因子，鞭毛蛋白FliZ。通过遗传和生化分析，我们发现FliZ在翻译后控制HilD正向调节hilA的表达。该机制独立于其他鞭毛成分，不通过负调节因子HilE或fliz介导的RpoS调节。我们证明FliZ控制HilD蛋白的活性而不是稳定性。FliZ在没有Lon蛋白酶的情况下调节HilD，先前显示可以降解HilD。事实上，FliZ，而不是HilD，似乎是Lon最相关的靶标，因为它与SPI1表达有关。缺乏FliZ的突变体在肠道定植的能力显著减弱，但在全身感染期间不受影响。肠道衰减部分依赖于SPI1，但FliZ具有额外的多效性作用。
A prerequisite for Salmonella enterica to cause both intestinal and systemic disease is the direct injection of effector proteins into host intestinal epithelial cells via a type three secretion system (T3SS); the T3SS genes are carried on Salmonella pathogenicity island 1 (SPI1). These effector proteins induce inflammatory diarrhea and bacterial invasion. Expression of the SPI1 T3SS is tightly regulated in response to environmental signals through a variety of global regulatory systems. We have previously shown that three AraC-like regulators, HilD, HilC, and RtsA, act in a complex feed-forward regulatory loop to control the expression of the hilA gene, which encodes the direct regulator of the SPI1 structural genes. In this work, we characterize a major positive regulator of this system, the flagellar protein FliZ. Through genetic and biochemical analyses, we show that FliZ posttranslationally controls HilD to positively regulate hilA expression. This mechanism is independent of other flagellar components and is not mediated through the negative regulator HilE or through FliZ-mediated RpoS regulation. We demonstrate that FliZ controls HilD protein activity and not stability. FliZ regulates HilD in the absence of Lon protease, previously shown to degrade HilD. Indeed, it appears that FliZ, rather than HilD, is the most relevant target of Lon as it relates to SPI1 expression. Mutants lacking FliZ are significantly attenuated in their ability to colonize the intestine but are unaffected during systemic infection. The intestinal attenuation is partially dependent on SPI1, but FliZ has additional pleiotropic effects.