Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Results Probl Cell Differ. 2020;69:137-176. doi: 10.1007/978-3-030-51849-3_5.
Bacteria participate in a wide diversity of symbiotic associations with eukaryotic hosts that require precise interactions for bacterial recognition and persistence. Most commonly, host-associated bacteria interfere with host gene expression to modulate the immune response to the infection. However, many of these bacteria also interfere with host cellular differentiation pathways to create a hospitable niche, resulting in the formation of novel cell types, tissues, and organs. In both of these situations, bacterial symbionts must interact with eukaryotic regulatory pathways. Here, we detail what is known about how bacterial symbionts, from pathogens to mutualists, control host cellular differentiation across the central dogma, from epigenetic chromatin modifications, to transcription and mRNA processing, to translation and protein modifications. We identify four main trends from this survey. First, mechanisms for controlling host gene expression appear to evolve from symbionts co-opting cross-talk between host signaling pathways. Second, symbiont regulatory capacity is constrained by the processes that drive reductive genome evolution in host-associated bacteria. Third, the regulatory mechanisms symbionts exhibit correlate with the cost/benefit nature of the association. And, fourth, symbiont mechanisms for interacting with host genetic regulatory elements are not bound by native bacterial capabilities. Using this knowledge, we explore how the ubiquitous intracellular Wolbachia symbiont of arthropods and nematodes may modulate host cellular differentiation to manipulate host reproduction. Our survey of the literature on how infection alters gene expression in Wolbachia and its hosts revealed that, despite their intermediate-sized genomes, different strains appear capable of a wide diversity of regulatory manipulations. Given this and Wolbachia's diversity of phenotypes and eukaryotic-like proteins, we expect that many symbiont-induced host differentiation mechanisms will be discovered in this system.
细菌参与广泛的共生关联与真核宿主，需要精确的相互作用，为细菌的识别和持久性。最常见的是，宿主相关的细菌干扰宿主基因表达，以调节对感染的免疫反应。然而，许多这些细菌也干扰宿主细胞分化途径，以创造一个适宜的小生境，导致新的细胞类型、组织和器官的形成。在这两种情况下，细菌共生体必须与真核调控途径相互作用。在这里，我们详细介绍了从病原体到共生体的细菌共生体如何控制宿主细胞分化跨越中心法则，从表观遗传染色质修饰到转录和 mRNA 处理，再到翻译和蛋白质修饰。我们从这个调查中确定了四个主要趋势。首先，控制宿主基因表达的机制似乎是从共生体共话宿主信号通路之间的交叉对话中进化而来的。其次，共生体的调节能力受到驱动宿主相关细菌还原基因组进化的过程的限制。第三，共生体表现出的调节机制与关联的成本/收益性质相关。第四，共生体与宿主遗传调控元件相互作用的机制不受固有细菌能力的限制。利用这些知识，我们探讨了普遍存在于节肢动物和线虫中的 Wolbachia 共生体如何通过调节宿主细胞分化来操纵宿主繁殖。我们对 Wolbachia 及其宿主中感染如何改变基因表达的文献进行了调查，结果表明，尽管它们的基因组中等大小，不同的菌株似乎能够进行广泛的调节操作。考虑到这一点，以及 Wolbachia 的多样性表型和真核样蛋白，我们预计在这个系统中将会发现许多共生体诱导的宿主分化机制。
