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DegP 参与肠致病性大肠杆菌中 Cpx 介导的 III 型分泌系统的转录后调控。

DegP is involved in Cpx-mediated posttranscriptional regulation of the type III secretion apparatus in enteropathogenic Escherichia coli.

机构信息

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.

出版信息

Infect Immun. 2012 May;80(5):1766-72. doi: 10.1128/IAI.05679-11. Epub 2012 Feb 13.

DOI:10.1128/IAI.05679-11
PMID:22331433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3347454/
Abstract

The Cpx envelope stress response facilitates adaptation to envelope stresses that lead to the misfolding of periplasmic proteins. Cpx-mediated adaptation involves elevated expression of periplasmic proteases and chaperones. Previously, we demonstrated that induction of the Cpx envelope stress response in enteropathogenic Escherichia coli (EPEC) also results in inhibition of type III secretion (T3S) and that this is correlated with downregulated transcription of the relevant genes. Here, we investigated whether the Cpx stress response might also exert posttranscriptional effects on the T3S apparatus. We show that DsbA is required for T3S, while removal of transcription factor CpxR or the Cpx-regulated folding factor CpxP or PpiA has minimal effects. Conversely, the entire T3S complex is removed from the envelope when the Cpx response is activated. Overexpression of the chaperone/protease DegP mimics the Cpx-dependent inhibition of the T3S complex at a posttranscriptional level, and mutation of degP partly abrogates the ability of the Cpx response to inhibit the T3S complex and motility. We present data that suggest that both the protease and chaperone activities of DegP are likely important for the impact on T3S. Altogether, our data indicate that DegP is normally a part of the Cpx-mediated inhibition of virulence determinant expression in EPEC and that additional factors are involved.

摘要

Cpx 信封应激反应有助于适应导致周质蛋白错误折叠的信封应激。Cpx 介导的适应涉及周质蛋白酶和伴侣的高水平表达。以前,我们证明了肠致病性大肠杆菌 (EPEC) 中 Cpx 信封应激反应的诱导也会导致 III 型分泌 (T3S) 的抑制,并且这与相关基因的转录下调相关。在这里,我们研究了 Cpx 应激反应是否也可能对 T3S 装置产生转录后效应。我们表明 DsbA 是 T3S 所必需的,而去除转录因子 CpxR 或 Cpx 调节的折叠因子 CpxP 或 PpiA 的影响最小。相反,当 Cpx 反应被激活时,整个 T3S 复合物从信封中被去除。伴侣/蛋白酶 DegP 的过表达模拟了 Cpx 依赖性的 T3S 复合物在转录后水平的抑制,并且 degP 的突变部分消除了 Cpx 反应抑制 T3S 复合物和运动性的能力。我们提供的数据表明,DegP 的蛋白酶和伴侣活性对于对 T3S 的影响都很重要。总之,我们的数据表明,DegP 通常是 EPEC 中 Cpx 介导的毒力决定因子表达抑制的一部分,并且涉及其他因素。

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本文引用的文献

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Genetic selection designed to stabilize proteins uncovers a chaperone called Spy.遗传选择设计用于稳定蛋白质,揭示了一种称为 Spy 的伴侣蛋白。
Nat Struct Mol Biol. 2011 Mar;18(3):262-9. doi: 10.1038/nsmb.2016. Epub 2011 Feb 13.
2
Structural basis for two-component system inhibition and pilus sensing by the auxiliary CpxP protein.辅助 CpxP 蛋白对二组分系统抑制和菌毛感应的结构基础。
J Biol Chem. 2011 Mar 18;286(11):9805-14. doi: 10.1074/jbc.M110.194092. Epub 2011 Jan 14.
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N-acetyllactosamine-induced retraction of bundle-forming pili regulates virulence-associated gene expression in enteropathogenic Escherichia coli.N-乙酰乳糖胺诱导的菌毛收缩调节肠致病性大肠杆菌中与毒力相关的基因表达。
Mol Microbiol. 2010 Jun 1;76(5):1111-26. doi: 10.1111/j.1365-2958.2010.07192.x. Epub 2010 May 4.
4
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Mol Microbiol. 2010 Jun 1;76(5):1095-110. doi: 10.1111/j.1365-2958.2010.07145.x. Epub 2010 Apr 14.
5
Molecular transformers in the cell: lessons learned from the DegP protease-chaperone.细胞中的分子转导器:从 DegP 蛋白酶-伴侣中获得的启示。
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Role of DegP for two-partner secretion in Bordetella.DegP在博德特氏菌双组分分泌中的作用。
Mol Microbiol. 2009 Oct;74(2):315-29. doi: 10.1111/j.1365-2958.2009.06860.x. Epub 2009 Aug 24.
7
Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli.大肠杆菌中保守丝氨酸蛋白酶 DegP 和 DegS 的结构、功能和调控。
Res Microbiol. 2009 Nov;160(9):660-6. doi: 10.1016/j.resmic.2009.07.012. Epub 2009 Aug 18.
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Role of periplasmic chaperones and BamA (YaeT/Omp85) in folding and secretion of intimin from enteropathogenic Escherichia coli strains.周质伴侣蛋白和BamA(YaeT/Omp85)在肠致病性大肠杆菌菌株中intimin折叠与分泌中的作用
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