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Differential Regulation of Salmonella typhimurium Type III Secreted Proteins by Pathogenicity Island 1 (SPI-1)-Encoded Transcriptional Activators InvF and HilA

机译:致病性岛1(SPI-1)编码转录激活因子InvF和HilA对鼠伤寒沙门氏菌III型分泌蛋白的差异调节。

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Salmonella enterica encodes a type III protein secretion system within a pathogenicity island (SPI-1) that is located at centisome 63 of its chromosome. This system is required for the ability of these bacteria to stimulate cellular responses that are essential for their pathogenicity. Expression of components and substrates of this system is subject to complex regulatory mechanisms. These mechanisms involve the function of HilA and InvF, two transcriptional regulatory proteins encoded within SPI-1. In this study, we examined the functional relationship between these two regulatory proteins. We found that strains carrying loss-of-function mutations in either hilA or invF differ in their ability to stimulate cellular responses. An S. typhimurium hilA mutant strain retained considerable signaling capacity that resulted in significant levels of internalization into host cells. In contrast, introduction of a nonpolar loss-of-function mutation ininvF rendered S. typhimurium significantly impaired in its ability to enter host cells. Consistent with these different phenotypes, we found that HilA and InvF control the expression of different genes. HilA regulates the expression of components of the type III secretion machinery, whereas InvF controls the expression of type III secreted proteins encoded outside of SPI-1. We also found that the expression of secreted proteins encoded within SPI-1 are under the control of both HilA and InvF. Our results therefore indicate that InvF and HilA differentially control the expression of components and substrates of the invasion-associated type III secretion system.
机译:肠沙门氏菌(Salmonella enterica)编码位于致病岛(SPI-1)内的III型蛋白质分泌系统,该岛位于其染色体的63位。这些细菌刺激其致病性必不可少的细胞反应的能力需要该系统。该系统的成分和底物的表达受制于复杂的调节机制。这些机制涉及HilA和InvF的功能,这是SPI-1中编码的两种转录调节蛋白。在这项研究中,我们检查了这两个调节蛋白之间的功能关系。我们发现,在 hilA invF 中带有功能丧失突变的菌株刺激细胞反应的能力不同。一个 S。鼠伤寒杆菌hilA 突变株保留了相当大的信号传递能力,导致显着水平的内在化进入宿主细胞。相反,在 invF 中引入非极性功能丧失突变会导致 S。鼠伤寒进入宿主细胞的能力明显受损。与这些不同的表型一致,我们发现HilA和InvF控制着不同基因的表达。 HilA调节III型分泌机制的成分的表达,而InvF控制SPI-1外部编码的III型分泌蛋白的表达。我们还发现SPI-1中编码的分泌蛋白的表达受HilA和InvF的控制。因此,我们的结果表明,InvF和HilA差异控制了与入侵相关的III型分泌系统的成分和底物的表达。

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