Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi.

Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi.
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对不可培养的机会性人类病原体,肠肠细胞生物的基因组调查。

DOI:
10.1371/journal.ppat.1000261
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发表时间:
2009-01
期刊:
影响因子:
6.7
通讯作者:
Tzipori S
Tzipori S
中科院分区:
医学1区
文献类型:
--
作者:
Akiyoshi DE;Morrison HG;Lei S;Feng X;Zhang Q;Corradi N;Mayanja H;Tumwine JK;Keeling PJ;Weiss LM;Tzipori S

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比氏肠细胞虫是与人类疾病相关的最常见的微孢子虫,特别是在免疫功能低下的人群中。在HIV感染的情况下,它与腹泻和消耗综合征有关。与所有微孢子虫一样,E. bieneusi是一种专性细胞内寄生虫,但与其他寄生虫不同,它与宿主细胞质直接接触。研究E.由于缺乏基因组数据和缺乏强大的培养系统,bieneusi受到很大限制。在这里,我们提出了第一个大规模的基因组数据集的E。谢谢通过配对末端桑格测序产生了约3.86 Mb的独特序列,占估计的6 Mb基因组的约64%。在E. bieneusi,其中1,702个编码具有指定功能的蛋白质。其中,653个是兔脑原虫蛋白的同源物。只有一个E。具有指定功能的bieneusi蛋白没有E.家兔同系物共享的蛋白质,一般来说,均匀分布在功能类别,除了缺乏基因编码的蛋白质与脂肪酸和核心碳代谢途径。在E. bieneusi基因组中,所有性状与基因组压实一致。我们的研究结果表明,E. bieneusi是极端基因组减少和宿主依赖的可能模型。 比氏肠细胞虫是一种临床上重要的病原体,与人类微孢子虫病,特别是在免疫功能低下的个人。E. bieneusi在哺乳动物中广泛存在,并且对于感染没有有效的商业治疗。病原体不易培养,动物模型有限。因此,我们进行了序列调查,并产生了第一个大规模的基因组数据集的E。bieneusi,我们用它来研究其基因组的组织和结构,并与另一种基因组已被完全测序的微孢子虫--兔脑孢子虫进行比较分析。急诊bieneusi基因组显示了许多与基因组紧密化相关的特征,包括高基因密度、短基因间隔区、缩短的蛋白质和很少的内含子。除了一个例外,所有的E。bieneusi蛋白具有E.家兔同系物我们发现编码与脂肪酸和碳代谢相关的蛋白质的基因很少。这些核心功能在细胞内寄生虫中减少的可能性是有趣的,但由于E。bieneusi的基因组是不完整的,我们不能排除在完整的基因组中发现与各种代谢途径相关的其他蛋白质的可能性。
Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence. Enterocytozoon bieneusi is a clinically significant pathogen associated with human microsporidiosis, particularly in immunocompromised individuals. E. bieneusi is widespread in mammals, and there is no effective commercial treatment for infection. The pathogen cannot be readily cultivated, and animal models are limited. We therefore undertook a sequence survey and generated the first large-scale genomic dataset for E. bieneusi, which we used to study the organization and structure of its genome and to perform a comparative analysis with Encephalitozoon cuniculi, another microsporidian whose genome has been completely sequenced. The E. bieneusi genome showed many traits associated with genome compaction including high gene density, short intergenic regions, shortened proteins, and few introns. With one exception, all E. bieneusi proteins with assigned functions had E. cuniculi homologs. We found a paucity of genes encoding proteins associated with fatty acid and carbon metabolism. The possibility that these core functions are reduced in an intracellular parasite is intriguing, but because the genome sequence of E. bieneusi is incomplete, we cannot exclude the possibility that additional proteins associated with the various metabolic pathways would be discovered in a completed genome.
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