Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Mol Microbiol. 2010 Jun 1;76(5):1095-110. doi: 10.1111/j.1365-2958.2010.07145.x. Epub 2010 Apr 14.
The Cpx envelope stress response is induced by the misfolding of periplasmic proteins and restores envelope homeostasis by upregulating several periplasmic protein folding and degrading factors. The Cpx response also regulates the expression of a variety of envelope-spanning protein complexes, including flagella, secretion systems and pili, which play an important role in pathogenesis. In a previous study, we inactivated the Cpx response in enteropathogenic Escherichia coli (EPEC), a causative agent of infant diarrhoea, and observed decreased expression of its major adhesin, the bundle-forming pilus (BFP). Here, we examined the mechanism underlying this BFP expression defect, and found that this phenotype can be attributed to insufficient expression of periplasmic folding factors, such as DsbA, DegP and CpxP. Hence, a low level of Cpx pathway activity promotes BFP synthesis by upregulating factors important for folding of BFP component proteins. Conversely, we found that full induction of the Cpx response inhibits BFP expression, mainly by repressing transcription of the bfp gene cluster. In combination with a previous report examining EPEC type III secretion, our results demonstrate that the Cpx response co-ordinates the repression of cell-surface structures during periods of envelope stress.
Cpx 外膜应激反应是由周质蛋白错误折叠诱导的，通过上调几种周质蛋白折叠和降解因子来恢复外膜的稳态。Cpx 反应还调节多种包膜贯穿蛋白复合物的表达，包括鞭毛、分泌系统和菌毛，这些在发病机制中起着重要作用。在之前的一项研究中，我们在肠致病性大肠杆菌（EPEC）中失活了 Cpx 反应，EPEC 是婴儿腹泻的病原体，我们观察到其主要粘附素束形成菌毛（BFP）的表达减少。在这里，我们研究了这种 BFP 表达缺陷的机制，发现这种表型可以归因于周质折叠因子如 DsbA、DegP 和 CpxP 的表达不足。因此，Cpx 途径活性的低水平通过上调 BFP 组成蛋白折叠的重要因子来促进 BFP 的合成。相反，我们发现 Cpx 反应的完全诱导抑制了 BFP 的表达，主要是通过抑制 bfp 基因簇的转录来实现的。结合之前关于肠致病性大肠杆菌 III 型分泌的报告，我们的结果表明 Cpx 反应协调了在 envelope stress 期间对细胞表面结构的抑制。
