Vogt Stefanie L, Raivio Tracy L
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9.
Mol Microbiol. 2014 May;92(4):681-97. doi: 10.1111/mmi.12581. Epub 2014 Apr 15.
Gram-negative bacteria possess several envelope stress responses that detect and respond to damage to this critical cellular compartment. The σ(E) envelope stress response senses the misfolding of outer membrane proteins (OMPs), while the Cpx two-component system is believed to detect the misfolding of periplasmic and inner membrane proteins. Recent studies in several Gram-negative organisms found that deletion of hfq, encoding a small RNA chaperone protein, activates the σ(E) envelope stress response. In this study, we assessed the effects of deleting hfq upon activity of the σ(E) and Cpx responses in non-pathogenic and enteropathogenic (EPEC) strains of Escherichia coli. We found that the σ(E) response was activated in Δhfq mutants of all E. coli strains tested, resulting from the misregulation of OMPs. The Cpx response was activated by loss of hfq in EPEC, but not in E. coli K-12. Cpx pathway activation resulted in part from overexpression of the bundle-forming pilus (BFP) in EPEC Δhfq. We found that Hfq repressed expression of the BFP via PerA, a master regulator of virulence in EPEC. This study shows that Hfq has a more extensive role in regulating the expression of envelope proteins and horizontally acquired virulence genes in E. coli than previously recognized.
革兰氏阴性菌具有多种包膜应激反应，可检测并应对这一关键细胞区室的损伤。σ(E)包膜应激反应可感知外膜蛋白（OMP）的错误折叠，而Cpx双组分系统据信可检测周质和内膜蛋白的错误折叠。最近在几种革兰氏阴性菌中的研究发现，编码小RNA伴侣蛋白的hfq缺失会激活σ(E)包膜应激反应。在本研究中，我们评估了缺失hfq对大肠杆菌非致病性和肠致病性（EPEC）菌株中σ(E)和Cpx反应活性的影响。我们发现，在所有测试的大肠杆菌菌株的Δhfq突变体中，σ(E)反应均被激活，这是由于OMP的调控异常所致。在EPEC中，hfq缺失会激活Cpx反应，但在大肠杆菌K-12中则不会。Cpx途径的激活部分是由于EPEC Δhfq中束状菌毛（BFP）的过度表达。我们发现，Hfq通过PerA抑制BFP的表达，PerA是EPEC中一种毒力主调节因子。本研究表明，Hfq在调节大肠杆菌包膜蛋白表达和水平获得的毒力基因方面的作用比以前认识到的更为广泛。
