Metagenome diversity illuminates origins of pathogen effectors.
Metagenome diversity illuminates origins of pathogen effectors.
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宏基因组多样性阐明了病原体效应子的起源。
DOI：
10.1101/2023.02.26.530123
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Gillespie,JosephJ
中科院分区：
文献类型：
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作者：
Verhoeve,VictoriaI;Lehman,StephanieS;Driscoll,TimothyP;Beckmann,JohnF;Gillespie,JosephJ
最近的宏基因组组装基因组（MAG）分析对立克次体学系统学产生了深远的影响。具有预测的细胞外生活方式的基础谱系（Mitibacteraceae 和 Athabascaceae）的发现揭示了向宿主依赖过渡的进化时间点，该时间点的发生独立于线粒体进化。值得注意的是，这些基础立克次体携带立克次体病毒同源物 (rvh) IV 型分泌系统 (T4SS)，据称利用 rvh 杀死同源微生物，而不是像派生立克次体病原体那样寄生宿主细胞。 MAG 分析还大大增加了立克次体属的多样性，并描绘了一个基础谱系（Tisiphia），该谱系预示着来自原生生物和无脊椎动物内共生体的人类病原体的增加。在此，我们探讨了立克次体 MAG 和立克次体 rvh 效应子分布的基因组多样性，以确定其起源。大多数立克次体 rvh 效应子在立克次体谱系之外的稀疏分布表明来自基础细胞外物种和其他立克次体科的独特 rvh 进化。值得注意的是，几乎每个效应子都以具有可变结构的多种不同形式被发现，阐明了基因复制和重组在塑造立克次体病原体效应子库中的深远作用。横向基因转移在塑造 rvh 效应子格局中发挥着重要作用，质粒和接合转座子上许多效应子的发现，以及立克次体和军团菌之间普遍存在的效应子基因交换都证明了这一点。我们的研究例证了 MAG 如何能够提供关于病原体效应子起源的令人难以置信的见解，以及它们的结构修饰如何适应真核宿主细胞生物学。
Recent metagenome assembled genome (MAG) analyses have profoundly impacted Rickettsiology systematics. Discovery of basal lineages (Mitibacteraceae and Athabascaceae) with predicted extracellular lifestyles reveals an evolutionary timepoint for the transition to host dependency, which occurred independent of mitochondrial evolution. Notably, these basal rickettsiae carry the Rickettsiales vir homolog (rvh) type IV secretion system (T4SS) and purportedly use rvh to kill congener microbes rather than parasitize host cells as described for derived rickettsial pathogens. MAG analysis also substantially increased diversity for genus Rickettsia and delineated a basal lineage (Tisiphia) that stands to inform on the rise of human pathogens from protist and invertebrate endosymbionts. Herein, we probed Rickettsiales MAG and genomic diversity for the distribution of Rickettsia rvh effectors to ascertain their origins. A sparse distribution of most Rickettsia rvh effectors outside of Rickettsiaceae lineages indicates unique rvh evolution from basal extracellular species and other rickettsial families. Remarkably, nearly every effector was found in multiple divergent forms with variable architectures, illuminating profound roles for gene duplication and recombination in shaping effector repertoires in Rickettsia pathogens. Lateral gene transfer plays a prominent role shaping the rvh effector landscape, as evinced by the discover of many effectors on plasmids and conjugative transposons, as well as pervasive effector gene exchange between Rickettsia and Legionella species. Our study exemplifies how MAGs can provide incredible insight on the origins of pathogen effectors and how their architectural modifications become tailored to eukaryotic host cell biology.