Schator Daniel, Gomez-Valero Laura, Buchrieser Carmen, Rolando Monica
Institut Pasteur, Université de Paris, CNRS UMR 3525, Unité Biologie des Bactéries Intracellulaires, F-75015 Paris, France.
Collège doctoral, Sorbonne Université, F-75005 Paris, France.
Microlife. 2021 Nov 29;2:uqab013. doi: 10.1093/femsml/uqab013. eCollection 2021.
In recent years, the interplay of epigenetics and infection moved into the limelight. Epigenetic regulation describes modifications in gene expression without alterations of the DNA sequence. In eukaryotes, this mechanism is central for fundamental cellular processes such as cell development and differentiation, but it is also involved in more specific tasks such as the response to infection by a pathogen. One of the most common types of epigenetic changes is the modification of histones. Histones, the small protein building blocks that are wrapped with DNA are the fundamental packaging unit of chromatin. Histones can be modified by linking different moieties to them-one of the most abundant ones is acetylation. Histone acetylation is regulated by two main classes of enzymes, histone acetyl transferases (HAT) and their counterparts, histone deacetylases (HDAC). Given the high abundance and importance in regulating gene expression, histone acetylation is an excellent target for pathogens to manipulate the host cell to their advantage. Targeting HDACs gained particular interest in recent years, due to the increased use of HDAC inhibitors in clinical practice. Recently, the possibility to fight an infection with HDAC inhibitors was suggested as an alternative to overcome the ever-growing problem of antibiotic resistance. In this review, we focus on the regulation of HDACs and their involvement in immune cell function. We then highlight different mechanisms employed by pathogens to manipulate histone deacetylases and we discuss the possibility of HDAC inhibitors as therapeutics to fight infections.
近年来，表观遗传学与感染之间的相互作用成为了焦点。表观遗传调控描述的是基因表达的修饰，而DNA序列并未改变。在真核生物中，这种机制对于细胞发育和分化等基本细胞过程至关重要，但它也参与了更具体的任务，例如对病原体感染的应答。最常见的表观遗传变化类型之一是组蛋白的修饰。组蛋白是与DNA缠绕在一起的小蛋白质构建块，是染色质的基本包装单元。组蛋白可以通过与不同的基团连接来进行修饰，其中最丰富的一种是乙酰化。组蛋白乙酰化由两类主要的酶调节，即组蛋白乙酰转移酶（HAT）及其对应物组蛋白去乙酰化酶（HDAC）。鉴于其在调节基因表达方面的高丰度和重要性，组蛋白乙酰化是病原体操纵宿主细胞以使其自身受益的一个极佳靶点。近年来，由于HDAC抑制剂在临床实践中的使用增加，靶向HDAC受到了特别关注。最近，有人提出用HDAC抑制剂对抗感染作为克服日益严重的抗生素耐药性问题的一种替代方法。在这篇综述中，我们重点关注HDAC的调节及其在免疫细胞功能中的作用。然后，我们强调病原体用来操纵组蛋白去乙酰化酶的不同机制，并讨论HDAC抑制剂作为抗感染治疗药物的可能性。
