Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium.
Orientia tsutsugamushi: comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium.
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恙虫病东方体（Ot）是一种人类立克次体病原体，是一种专性细胞内革兰氏阴性菌，拥有所有生物中最为高度碎片化和重复的基因组之一。其约2.3 - Mb的基因组中约50%由重复DNA组成，这些重复DNA来源于高度增殖的立克次体扩增遗传元件（RAGE）。RAGE是一种整合和接合元件（ICE），在单个Ot基因组中多达93个拷贝，其中大多数部分或严重降解。在本报告中，我们分析了8个全测序的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，包括那些编码DNA移动蛋白、P型（vir）和F型（tra）Ⅳ型分泌系统（T4SS）组件、含锚蛋白重复序列和四肽重复序列的效应蛋白以及其他搭载的货物基因。最初，Ot中严重降解的RAGE导致人们推测它们是不再活跃的历史ICE的残余物。然而，我们的分析确定了两个Ot基因组含有一个或多个完整的RAGE，其具有对介导ICE DNA转移至关重要的完整F - T4SS基因。由于在不相关的立克次体物种中也发现了类似的ICE，我们断言RAGE可能在立克次体的横向基因转移中持续发挥作用。我们还在所有Ot基因组中鉴定出一组保守的基因转移因子基因。这些发现共同表明，尽管Ot具有专性细胞内的生存方式且宿主范围局限于螨、啮齿动物和人类，但其基因组是高度动态的，并通过移动遗传元件和类病毒元件的持续入侵而形成。
专性细胞内细菌，即那些只能在其他活细胞内生长的细菌，由于其孤立的复制生态位，与其他微生物进行水平基因转移的机会有限。人类病原体Ot是一种引起恙虫病的专性细胞内细菌，它编码一种约40个基因的移动遗传元件的异常高拷贝数，这种元件通常有助于微生物间的基因转移。这种增殖的元件在Ot中严重降解，先前被认为是不活跃的。在这里，我们对8个Ot菌株中的这种元件进行了详细分析，并发现两个菌株至少有一个完整拷贝。这意味着该元件仍然能够在Ot种群中移动，并表明这种细菌的基因组可能比先前认为的更具动态性。我们的工作引发了关于细胞内微生物进化的问题，并为基于基因的恙虫病诊断和防治工作敲响了警钟。
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 composed 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 93 copies, most of which are partially or heavily degraded. In this report, we analyzed RAGEs in eight fully sequenced Ot genomes and manually curated and re-annotated all RAGE-associated genes, including those encoding DNA mobilization 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 Originally, the heavily degraded Ot RAGEs have led to speculation that they are remnants of historical ICEs that are no longer active. Our analysis, however, identified two Ot genomes harboring 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 may play an ongoing role in lateral gene transfer within the Rickettsiales. We also identified a conserved set of gene transfer agent genes in all Ot genomes. 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 virus-like elements. Obligate intracellular bacteria, or those only capable of growth inside other living cells, have limited opportunities for horizontal gene transfer with other microbes due to their isolated replicative niche. The human pathogen Ot, an obligate intracellular bacterium causing scrub typhus, encodes an unusually high copy number of a ~40 gene mobile genetic element that typically facilitates genetic transfer across microbes. This proliferated element is heavily degraded in Ot and previously assumed to be inactive. Here, we conducted a detailed analysis of this element in eight Ot strains and discovered two strains with at least one intact copy. This implies that the element is still capable of moving across Ot populations and suggests that the genome of this bacterium may be even more dynamic than previously appreciated. Our work raises questions about intracellular microbial evolution and sounds an alarm for gene-based efforts focused on diagnosing and combatting scrub typhus.
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