G5 Chromatine et Infection, Institut Pasteur, 75015, Paris, France.
Université de Paris, Sorbonne Paris Cité, Paris, France.
Semin Immunopathol. 2020 Apr;42(2):201-213. doi: 10.1007/s00281-019-00778-9. Epub 2020 Feb 4.
In the long co-evolution of host-pathogen interaction, bacteria have developed sophisticated strategies to manipulate host cell mechanisms and reprogram host transcription. Targeting chromatin, mainly through post-translational modification (PTM) of histone proteins, is one strategy that has been revealed over the last decade. Indeed, histone modifications play a crucial role in regulating transcription during cell type and stimulus specific responses, making them good targets during infection. Therefore, the study of host-pathogen interactions provides breakthroughs in understanding virulence mechanisms, but also in host cell mechanisms. Although chromatin is regulated by DNA methylation, noncoding RNAs, and post-translational modifications of histones, most studies have concentrated on bacteria-induced histone modifications, which will be the focus of this review. We will discuss the different mechanisms used by bacteria to induce histone PTMs, whether it is through direct targeting of pathogen effector enzymes, or indirectly through modulation of cellular signaling cascade. We will summarize the concepts we learned in cell biology from exploring bacteria-triggered histone modifications, by focusing on the signaling cascades modified by bacteria, bacterial mimics of eukaryotic enzymes, and the novel histone marks imposed upon infection.
在宿主-病原体相互作用的漫长共同进化过程中,细菌已经发展出了复杂的策略来操纵宿主细胞机制并重新编程宿主转录。靶向染色质,主要通过组蛋白蛋白质的翻译后修饰(PTM),是过去十年中揭示的一种策略。事实上,组蛋白修饰在调节细胞类型和刺激特异性反应过程中的转录中起着至关重要的作用,使它们成为感染期间的良好靶标。因此,宿主-病原体相互作用的研究为理解毒力机制提供了突破,也为宿主细胞机制提供了突破。尽管染色质受 DNA 甲基化、非编码 RNA 和组蛋白翻译后修饰的调节,但大多数研究都集中在细菌诱导的组蛋白修饰上,这将是本综述的重点。我们将讨论细菌用于诱导组蛋白 PTM 的不同机制,无论是通过病原体效应酶的直接靶向,还是通过细胞信号级联的间接调节。我们将通过关注被细菌修饰的信号级联、真核酶的细菌模拟物以及感染时施加的新型组蛋白标记,总结我们从探索细菌触发的组蛋白修饰中学到的细胞生物学概念。