Bacterial nucleomodulins: A coevolutionary adaptation to the eukaryotic command center.
Bacterial nucleomodulins: A coevolutionary adaptation to the eukaryotic command center.
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DOI：
10.1371/journal.ppat.1009184
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发表时间：
2021-01
期刊：
影响因子：
6.7
通讯作者：
Abu Kwaik Y
中科院分区：
文献类型：
--
作者：
Hanford HE;Von Dwingelo J;Abu Kwaik Y
通过与宿主的长期相互作用，细菌病原体已经进化出独特的效应蛋白库，这些效应蛋白与特定的宿主靶标相互作用，并将宿主细胞重新编程为允许病原体增殖的小生境。靶向效应蛋白进入宿主细胞核以调节核过程是细菌病原体中的一个新兴主题。这些独特的病原体效应蛋白近年来被称为“核调节蛋白”。第一个核调节蛋白是在植物病原体农杆菌和黄单胞菌中发现的，其中它们的核调节蛋白分别作为真核转录因子或将自身整合到宿主细胞DNA中以促进肿瘤诱导。最近在哺乳动物病原体中鉴定出许多核调节蛋白。细菌核调节蛋白是一个新兴的病原体效应蛋白家族，其通过各种机制进化为靶向宿主细胞指挥中心的特定组分。这些机制包括：染色质动力学、组蛋白修饰、DNA甲基化、RNA剪接、DNA复制、细胞周期和细胞信号传导途径。核调节蛋白可以诱导宿主细胞的短期或长期表观遗传修饰。在这篇广泛的综述中，我们讨论了植物和哺乳动物病原体的核调节蛋白的现有知识。虽然许多核调节蛋白已经被确定，但继续研究有助于了解它们的作用机制以及它们在发病过程中所起的作用。对核调节蛋白的继续研究将增强我们对核染色质动力学、蛋白质稳态、转录景观和整个宿主细胞表观基因组的影响的认识。细菌病原体已经进化出一系列不同的效应蛋白，这些效应蛋白被分泌或注射到宿主细胞胞质溶胶中，将宿主细胞重编程到更有利的环境中。这些病原体中的许多具有调节宿主细胞基因表达而不改变细胞基因组序列的核靶向效应蛋白（核调节蛋白）。通过利用通过进化获得的核调节蛋白，病原体可以操纵宿主细胞的基因调节并改变宿主对感染的免疫反应。在这里，我们提供了一个全面的审查，讨论了不同阵列的核调节蛋白的目标和调节宿主基因组，通过干扰染色质动力学，组蛋白修饰，转录调控，干扰细胞周期，调节细胞信号通路的免疫反应。这种通过细菌核调节蛋白对宿主细胞基因调控的独特靶向是一个新兴的主题，并且可能是关于宿主指挥中心水平上的宿主-病原体相互作用的冰山一角。
Through long-term interactions with their hosts, bacterial pathogens have evolved unique arsenals of effector proteins that interact with specific host targets and reprogram the host cell into a permissive niche for pathogen proliferation. The targeting of effector proteins into the host cell nucleus for modulation of nuclear processes is an emerging theme among bacterial pathogens. These unique pathogen effector proteins have been termed in recent years as “nucleomodulins.” The first nucleomodulins were discovered in the phytopathogens Agrobacterium and Xanthomonas, where their nucleomodulins functioned as eukaryotic transcription factors or integrated themselves into host cell DNA to promote tumor induction, respectively. Numerous nucleomodulins were recently identified in mammalian pathogens. Bacterial nucleomodulins are an emerging family of pathogen effector proteins that evolved to target specific components of the host cell command center through various mechanisms. These mechanisms include: chromatin dynamics, histone modification, DNA methylation, RNA splicing, DNA replication, cell cycle, and cell signaling pathways. Nucleomodulins may induce short- or long-term epigenetic modifications of the host cell. In this extensive review, we discuss the current knowledge of nucleomodulins from plant and mammalian pathogens. While many nucleomodulins are already identified, continued research is instrumental in understanding their mechanisms of action and the role they play during the progression of pathogenesis. The continued study of nucleomodulins will enhance our knowledge of their effects on nuclear chromatin dynamics, protein homeostasis, transcriptional landscapes, and the overall host cell epigenome. Bacterial pathogens have evolved a repertoire of diverse effector proteins that are secreted or injected into the host cell cytosol, reprogramming the host cell into a more favorable environment. Many of these pathogens possess nuclear-targeted effector proteins (nucleomodulins) that modulate host cell gene expression without altering the cellular genomic sequence. By utilizing nucleomodulins obtained through evolution, pathogens can manipulate host cell gene regulation and alter host immune response to infection. Here, we provide a comprehensive review discussing a diverse array of nucleomodulins that target and modulate the host genome through interference with chromatin dynamics, histone modifications, regulation of transcription, interference of the cell cycle, and regulation of cell signaling pathways for immune response. This unique targeting of host cell gene regulation through bacterial nucleomodulins is an emerging theme and likely the tip of an iceberg regarding host–pathogen interactions at the level of the host command center.
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