CsrA and CsrB are required for the post-transcriptional control of the virulence-associated effector protein AvrA of Salmonella enterica

CsrA and CsrB are required for the post-transcriptional control of the virulence-associated effector protein AvrA of Salmonella enterica
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DOI:
10.1016/j.ijmm.2008.09.001
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发表时间:
2009-06-01
影响因子:
4.1
通讯作者:
Yaron, Sima
Yaron, Sima
中科院分区:
医学3区
文献类型:
--
作者:
Kerrinnes, Tobias;Zelas, Zohar Ben-Barak;Yaron, Sima

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肠炎沙门氏菌毒力相关效应蛋白AvrA是一种泛素样乙酰转移酶/半胱氨酸蛋白酶,干扰靶生物免疫应答的第一线。与肠球菌Avra蛋白的翻译不同,Avra蛋白的翻译要么是结构性的(I类菌株),要么是在酸诱导后进行的(2类菌株),要么根本不发生(3类菌株);相应Avra基因的结构性转录与这些定义的表达类别无关。当使用携带相应克隆的Avra基因及其启动子区域的质粒来实验增加Avra基因和mRNA分子的数量时,Avra mRNA在所有相应的Avra表达类中都发生了非常强烈的翻译。Avra的这种复制依赖的转录后控制依赖于CSRA/CsrB系统的调节作用,因为这两个基因的缺失完全取消了测试菌株中的翻译,而转录仍然没有受到影响。此外,携带克隆的AvrA基因的菌株的Avra的产生仍然依赖于CSRA的存在,但在csrB突变菌株中不受影响。另一方面,在携带克隆的CsrA和CsrB基因的肠球菌中,调控分子CsrA和CsrB的过量生产再次停止了Avra的表达。因此,Avra的表达被认为是由临界和有效浓度的CSRA(SEW-SAW调节)以转录后的方式调节的,这是通过CsrB的隔离活性实现的。(C)2008年爱思唯尔股份有限公司。版权所有。
The virulence-associated effector protein AvrA of Salmonella enterica is an ubiquitin-like acetyltransferase/cysteine protease, which interferes with the first line of immune response of the target organism. In contrast to translation of the AvrA protein in S. enterica strains, which takes place either constitutively (class I strains), or after acid induction (class 2 strains), or not at all (class 3 strains); the constitutive transcription of the respective avrA genes occurs regardless of these defined expression classes. When the number of avrA genes and mRNA molecules is raised experimentally using plasmids carrying the respective cloned avrA genes together with their promoter regions, the translation of avrA mRNA takes place very strongly in all respective AvrA expression classes. This kind of copy-dependent, post-transcriptional control of AvrA was shown to be dependent on the regulatory action of the CsrA/CsrB system since the deletion of both genes completely abolished the translation in the tested S. enterica strains, whereas the transcription remained unaffected. Moreover, AvrA production in strains carrying the cloned avrA genes on plasmids remained dependent on the presence of CsrA but unaffected in csrB mutant strains. On the other hand, overproduction of the regulatory molecules CsrA and CsrB in S. enterica strains carrying cloned csrA and csrB genes on plasmids ceased the expression of AvrA again. Therefore, the expression of avrA is suggested to be regulated in a post-transcriptional manner by critical and effective concentrations of CsrA (see-saw regulation), which is achieved through the sequestering activity of CsrB. (c) 2008 Elsevier GmbH. All rights reserved.