Pivotal role of the Francisella tularensis heat-shock sigma factor RpoH
Pivotal role of the Francisella tularensis heat-shock sigma factor RpoH
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DOI：
10.1099/mic.0.029058-0
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发表时间：
2009-08-01
期刊：
影响因子：
2.8
通讯作者：
Meibom, Karin L.
中科院分区：
文献类型：
--
作者：
Grall, Nathalie;Livny, Jonathan;Meibom, Karin L.
土拉热弗朗西斯菌是一种高度传染性的病原体，感染动物和人类引起土拉菌病。这种细菌的主要目标是巨噬细胞，它在逃离最初的吞噬体区室后在细胞质中复制。在巨噬细胞内复制的能力依赖于一系列基因的严格调控表达。协调细菌中多个基因调控的最常用手段之一是将专用的替代σ因子与RNA聚合酶（RNAP）的核心相关联。通过对土拉菌LVS基因组的计算机分析，我们发现除了编码RNAP核心的基因外，（包括α 1、α 2、β、β '和ω亚基），一个基因（表示为rpoD），其编码主西格玛因子西格玛（70），和编码σ（32）热休克家族的推定的替代σ因子同源物（命名为rpoH.因此，F.土拉热菌代表少数细菌物种之一，其除了主要因子σ之外仅具有一个或不具有替代σ因子（70）。在目前的工作中，我们证明了FTL_0851编码了一个真正的sigma（32）因子。土拉热杆菌LVS热应激反应的转录组学分析允许鉴定一系列已知热休克基因的直系同源物（包括Hsp40、GroEL、GroES、DnaK、DnaJ、GrpE、ClpB和ClpP的基因）和涉及弗朗西斯菌毒力的许多基因。生物信息学分析被用来识别前面有一个假定的sigma（32）结合位点的基因，揭示了与大肠杆菌中RpoH介导的基因表达的相似性和差异。我们的研究结果表明，RpoH是F.土拉热菌，并积极调节一个子集的基因参与热休克反应。
Francisella tularensis is a highly infectious pathogen that infects animals and humans to cause the disease tularemia. The primary targets of this bacterium are macrophages, in which it replicates in the cytoplasm after escaping the initial phagosomal compartment. The ability to replicate within macrophages relies on the tightly regulated expression of a series of genes. One of the most commonly used means of coordinating the regulation of multiple genes in bacteria consists of the association of dedicated alternative sigma factors with the core of the RNA polymerase (RNAP). In silico analysis of the F tularensis LVS genome led us to identify, in addition to the genes encoding the RNAP core (comprising the alpha 1, alpha 2, beta, beta' and omega subunits), one gene (designated rpoD) encoding the major sigma factor sigma(70), and a unique gene (FTL_0851) encoding a putative alternative sigma factor homologue of the sigma(32) heat-shock family (designated rpoH. Hence, F. tularensis represents one of the minority of bacterial species that possess only one or no alternative sigma factor in addition to the main factor sigma(70). In the present work, we show that FTL_0851 encodes a genuine sigma(32) factor. Transcriptomic analyses of the F, tularensis LVS heat-stress response allowed the identification of a series of orthologues of known heat-shock genes (including those for Hsp40, GroEL, GroES, DnaK, DnaJ, GrpE, ClpB and ClpP) and a number of genes implicated in Francisella virulence. A bioinformatic analysis was used to identify genes preceded by a putative sigma(32)-binding site, revealing both similarities to and differences from RpoH-mediated gene expression in Escherichia coli. Our results suggest that RpoH is an essential protein of F. tularensis, and positively regulates a subset of genes involved in the heat-shock response.