The Multifaceted Activity of the VirF Regulatory Protein in the Shigella Lifestyle.
The Multifaceted Activity of the VirF Regulatory Protein in the Shigella Lifestyle.
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DOI：
10.3389/fmolb.2016.00061
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发表时间：
2016
影响因子：
5
通讯作者：
Prosseda G
中科院分区：
文献类型：
--
作者：
Di Martino ML;Falconi M;Micheli G;Colonna B;Prosseda G
志贺氏菌是一种高度适应的人类病原体，主要在发展中国家发现并引起严重的肠道综合征。志贺氏菌高度复杂的感染策略依赖于入侵肠上皮屏障并引起其炎症破坏的能力。志贺氏菌病的细胞发病机制和临床表现是主要位于大毒力质粒（pINV）上的大量细菌毒力因子复杂作用的总和。pINV基因的表达受多种环境刺激的调控，包括由pINV和染色体编码的蛋白和sRNAs。毒力表型的主要调节剂是VirF，一种属于AraC转录调节剂家族的dna结合蛋白。位于pINV上的virF基因仅在宿主内表达，主要是为了响应细菌从外部环境过渡到肠道环境时发生的温度转变。然后VirF作为抗h - ns蛋白，直接激活icsA和virB基因，触发志贺氏菌侵袭程序的充分表达。在这篇综述中，我们将重点关注VirF的结构，其复杂的调控，以及它在志贺氏菌从非侵入性表型到侵入性表型的过程中所起的主要作用。我们还将讨论VirF在宿主体内抵抗不利条件的机制中的作用，这表明这种蛋白质正在成为一种全球性的调节剂，其作用不仅限于毒力系统。最后，我们将讨论最近的观察结果，赋予VirF作为志贺氏菌病的新型抗菌靶点的潜力。
Shigella is a highly adapted human pathogen, mainly found in the developing world and causing a severe enteric syndrome. The highly sophisticated infectious strategy of Shigella banks on the capacity to invade the intestinal epithelial barrier and cause its inflammatory destruction. The cellular pathogenesis and clinical presentation of shigellosis are the sum of the complex action of a large number of bacterial virulence factors mainly located on a large virulence plasmid (pINV). The expression of pINV genes is controlled by multiple environmental stimuli through a regulatory cascade involving proteins and sRNAs encoded by both the pINV and the chromosome. The primary regulator of the virulence phenotype is VirF, a DNA-binding protein belonging to the AraC family of transcriptional regulators. The virF gene, located on the pINV, is expressed only within the host, mainly in response to the temperature transition occurring when the bacterium transits from the outer environment to the intestinal milieu. VirF then acts as anti-H-NS protein and directly activates the icsA and virB genes, triggering the full expression of the invasion program of Shigella. In this review we will focus on the structure of VirF, on its sophisticated regulation, and on its role as major player in the path leading from the non-invasive to the invasive phenotype of Shigella. We will address also the involvement of VirF in mechanisms aimed at withstanding adverse conditions inside the host, indicating that this protein is emerging as a global regulator whose action is not limited to virulence systems. Finally, we will discuss recent observations conferring VirF the potential of a novel antibacterial target for shigellosis.