Salmonella SirA is a global regulator of genes mediating enteropathogenesis
Salmonella SirA is a global regulator of genes mediating enteropathogenesis
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DOI：
10.1046/j.1365-2958.1999.01244.x
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发表时间：
1999-02-01
影响因子：
3.6
通讯作者：
Heffron, F
中科院分区：
文献类型：
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作者：
Ahmer, BMM;van Reeuwijk, J;Heffron, F
已知鼠伤寒沙门氏菌SIRA调控沙门氏菌致病岛1(SPI1)中的hila和prgH基因。为了确定SIRA调节子的更多成员，我们筛选了10000个随机的lacZY融合(染色体MudJ插入)以供Sira调控，并鉴定了10个正调控的融合。三个融合在SPI1基因hiIA(SPI1转录调节基因)、spas(SPI1III型输出装置的组成部分)和sips(SPI1输出装置的底物)中。在SopB基因(也称为sigD)内有两次融合。SopB位于SPI5内，但编码通过SPI1输出装置输出的蛋白质。此外，5个融合基因位于SPI4的未知功能基因内，由于SPA和SIPB可能是Hila依赖的，我们测试了所有的融合(Hila除外)对Hila的依赖。令人惊讶的是，我们发现所有的融合都需要HILA来表达，而以质粒编码的SIRA无法绕过这一要求。因此，SIRA调节HILA，其产物调节SPI1、SPI4和SPI5内的基因，SIRA和HILA突变体在牛胃肠炎模型中都显著减弱，但在伤寒小鼠模型中几乎没有影响。本研究建立了SIRA/HiIA调节级联作为控制鼠伤寒沙门氏菌致病毒力功能的主要调控因子，因为鼠伤寒沙门氏菌可引起牛和人的胃肠炎，我们认为这一信息可能直接适用于人类疾病。
SirA of Salmonella typhimurium is known to regulate the hilA and prgH genes within Salmonella pathogenicity island 1 (SPI1). To identify more members of the SirA regulon, we screened 10 000 random lacZY fusions (chromosomal MudJ insertions) for regulation by SirA and identified 10 positively regulated fusions. Three fusions were within the SPI1 genes hiIA (an SPI1 transcriptional regulator), spaS (a component of the SPI1 type III export apparatus) and sipS (a substrate of the SPI1 export apparatus). Two fusions were within the sopB gene (also known as sigD). sopB is located within SPI5, but encodes a protein that is exported via the SPI1 export apparatus. In addition, five fusions were within genes of unknown function that are located in SPI4, As spaS and sipB were likely to be hilA dependent, we tested all of the fusions (except hilA) for hilA dependence. Surprisingly, we found that all of the fusions require hilA for expression and that plasmid-encoded SirA cannot bypass this requirement. Therefore, SirA regulates hilA, the product of which regulates genes within SPI1, SPI4 and SPI5, Both sirA and hilA mutants are dramatically attenuated in a bovine model of gastroenteritis, but have little or no effect in the mouse model of typhoid fever. This study establishes the SirA/HiIA regulatory cascade as the primary regulon controlling enteropathogenic virulence functions in S. typhimurium, Because S. typhimurium causes gastroenteritis in both cattle and humans, we believe that this information may be directly applicable to the human disease.