A pair of highly conserved two-component systems participates in the regulation of the hypervariable FIR proteins in different Legionella species
A pair of highly conserved two-component systems participates in the regulation of the hypervariable FIR proteins in different Legionella species
复制标题
DOI：
10.1128/jb.01742-06
复制
发表时间：
2007-05-01
影响因子：
3.2
通讯作者：
Segal, Gil
中科院分区：
文献类型：
--
作者：
Feldman, Michal;Segal, Gil
嗜肺军团菌和其他致病性军团菌通过使用Icm/Dot IV型分泌系统在原生动物和人类巨噬细胞内繁殖。具有孔形成活性的IcmQ蛋白和作为其伴侣蛋白的IcmR是该系统的两个基本组分。以前的研究表明，在29个军团菌属物种中，一个大的高变基因家族（FIR基因）位于保守的icmQ基因的上游，但尽管是非同源的，FIR蛋白被发现与其相应的IcmQ蛋白功能相似。29个冷杉基因的调控区的比对显示，它们可以分为三个调控组;第一组包含CpxR反应调节剂的结合位点，该位点先前被证明可以调节L.第二组包含CpxR结合位点和一个额外的调节元件，在此被鉴定为PmrA结合位点;第三组仅包含PmrA结合位点。两个冷杉基因，其中包括在CpxR和PmrA的共识序列，一个受控的表达系统，以及检查直接结合迁移率变动分析的取代的调控区的分析表明，CpxR和PmrA积极调节表达的冷杉基因，包含两个调控元件。在进化过程中发生的冷杉基因的调节变化可能是不同军团菌物种适应其特定环境宿主所必需的。
Legionella pneumophila and other pathogenic Legionella species multiply inside protozoa and human macrophages by using the Icm/Dot type IV secretion system. The IcmQ protein, which possesses pore-forming activity, and IcmR, which functions as its chaperone, are two essential components of this system. It was previously shown that in 29 Legionella species, a large hypervariable-gene family (fir genes) is located upstream from a conserved icmQ gene, but although nonhomologous, the FIR proteins were found to function similarly together with their corresponding IcmQ proteins. Alignment of the regulatory regions of 29 fir genes revealed that they can be divided into three regulatory groups; the first group contains a binding site for the CpxR response regulator, which was previously shown to regulate the L. pneumophila fir gene (icmR); the second group, which includes most of the fir genes, contains the CpxR binding site and an additional regulatory element that was identified here as a PmrA binding site; and the third group contains only the PmrA binding site. Analysis of the regulatory region of two fir genes, which included substitutions in the CpxR and PmrA consensus sequences, a controlled expression system, as well as examination of direct binding with mobility shift assays, revealed that both CpxR and PmrA positively regulate the expression of the fir genes that contain both regulatory elements. The change in the regulation of the fir genes that occurred during the course of evolution might be required for the adaptation of the different Legionella species to their specific environmental hosts.