Orientia tsutsugamushi: analysis of the mobilome of a highly fragmented and repetitive genome reveals ongoing lateral gene transfer in an obligate intracellular bacterium.
Orientia tsutsugamushi: analysis of the mobilome of a highly fragmented and repetitive genome reveals ongoing lateral gene transfer in an obligate intracellular bacterium.
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恙虫病东方体（Orientia tsutsugamushi）：对高度片段化和重复基因组的移动组的分析揭示了专性细胞内细菌中正在进行的横向基因转移。
DOI：
10.1101/2023.05.11.540415
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Salje,Jeanne
中科院分区：
文献类型：
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作者：
Giengkam,Suparat;Kullapanich,Chitrasak;Wongsantichon,Jantana;Adcox,HaleyE;Gillespie,JosephJ;Salje,Jeanne
恙虫病立克次体是一种专性的细胞内革兰氏阴性细菌，具有最高的片段化和重复性。其2.3Mb基因组中约50%由高度增殖的立克次体扩增遗传元件(RAGE)衍生的重复DNA组成。RAGE是一种整合和结合元件(ICE)，存在于单个OT基因组中，最多有92个拷贝，其中大部分被部分或严重降解。在这份报告中，我们分析了八个完全测序的OT基因组中的RAGE，并手动整理和重新注释了所有与RAGE相关的基因，包括编码DNA动员蛋白、P型(VIR)和F型(TrA)IV型分泌系统(T4SS)组件的基因、含有Ankyrin重复和四肽重复的效应器，以及其他搭载货物。最初，严重退化的OT狂暴导致人们猜测它们是不再活跃的历史冰层的残留物。然而，我们的分析鉴定了两个OT基因组，它们含有一个或多个完整的RAGE，具有介导ICE DNA转移所必需的完整的F-T4SS基因。由于在不相关的立克次体物种中发现了类似的冰，我们断言RAGE在立克次体内的横向基因转移中发挥着持续的作用。值得注意的是，我们还在几个OT基因组中发现了与其他立克次体前驱体没有相似之处的前驱体残留物。综上所述，这些发现表明，尽管OT基因组的细胞内生活方式和宿主范围仅限于螨类、啮齿动物和人类，但OT基因组是高度动态的，并通过移动遗传元件和病毒的持续入侵而形成。
The rickettsial human pathogen Orientia tsutsugamushi (Ot) is an obligate intracellular Gram-negative bacterium with one of the most highly fragmented and repetitive genomes of any organism. Around 50% of its ~2.3 Mb genome is comprised of repetitive DNA that is derived from the highly proliferated Rickettsiales amplified genetic element (RAGE). RAGE is an integrative and conjugative element (ICE) that is present in a single Ot genome in up to 92 copies, most of which are partially or heavily degraded. In this report, we analysed RAGEs in eight fully sequenced Ot genomes and manually curated and reannotated all RAGE-associated genes, including those encoding DNA mobilisation proteins, P-type (vir) and F-type (tra) type IV secretion system (T4SS) components, Ankyrin repeat- and tetratricopeptide repeat-containing effectors, and other piggybacking cargo. Originally, the heavily degraded Ot RAGEs led to speculation that they are remnants of historical ICEs that are no longer active. Our analysis, however, identified two Ot genomes harbouring one or more intact RAGEs with complete F-T4SS genes essential for mediating ICE DNA transfer. As similar ICEs have been identified in unrelated rickettsial species, we assert that RAGEs play an ongoing role in lateral gene transfer within the Rickettsiales. Remarkably, we also identified in several Ot genomes remnants of prophages with no similarity to other rickettsial prophages. Together these findings indicate that, despite their obligate intracellular lifestyle and host range restricted to mites, rodents and humans, Ot genomes are highly dynamic and shaped through ongoing invasions by mobile genetic elements and viruses.