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复发性疟原虫的复制期和休眠期肝脏阶段的比较转录组学分析。

A comparative transcriptomic analysis of replicating and dormant liver stages of the relapsing malaria parasite .

机构信息

Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, Netherlands.

Novartis Institutes for BioMedical Research, Basel, Switzerland.

出版信息

Elife. 2017 Dec 7;6:e29605. doi: 10.7554/eLife.29605.

Abstract

liver hypnozoites, which cause disease relapse, are widely considered to be the last barrier towards malaria eradication. The biology of this quiescent form of the parasite is poorly understood which hinders drug discovery. We report a comparative transcriptomic dataset of replicating liver schizonts and dormant hypnozoites of the relapsing parasite . Hypnozoites express only 34% of physiological pathways, while 91% are expressed in replicating schizonts. Few known malaria drug targets are expressed in quiescent parasites, but pathways involved in microbial dormancy, maintenance of genome integrity and ATP homeostasis were robustly expressed. Several transcripts encoding heavy metal transporters were expressed in hypnozoites and the copper chelator neocuproine was cidal to all liver stage parasites. This transcriptomic dataset is a valuable resource for the discovery of vaccines and effective treatments to combat vivax malaria.

摘要

肝休眠子是导致疾病复发的根源,被广泛认为是消灭疟疾的最后一道障碍。这种寄生虫休眠形式的生物学特性尚不清楚,这阻碍了药物的发现。我们报告了一个关于复发性寄生虫复制性肝裂殖体和休眠性肝休眠子的比较转录组数据集。休眠子仅表达生理途径的 34%,而复制性肝裂殖体中表达 91%。在休眠寄生虫中表达的已知疟疾药物靶点很少,但参与微生物休眠、基因组完整性维持和 ATP 动态平衡的途径得到了强烈表达。几种编码重金属转运蛋白的转录本在休眠子中表达,铜螯合剂 neocuproine 对所有肝期寄生虫均具有杀伤作用。这个转录组数据集是发现疫苗和有效治疗方法来对抗间日疟的宝贵资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d826/5758109/ca3027dd919a/elife-29605-fig1.jpg

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