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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A combined transcriptome and proteome survey of malaria parasite liver stages
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A combined transcriptome and proteome survey of malaria parasite liver stages

机译：疟原虫肝分期的转录组和蛋白质组研究

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For 50 years since their discovery, the malaria parasite liver stages (LS) have been difficult to analyze, impeding their utilization as a critical target for antiinfection vaccines and drugs. We have ur dertaken a comprehensive transcriptome analysis in combination with a proteomic survey of LS. Green fluorescent protein-tagged Plasmodium yoelii (PyGFP) was used to efficiently isolate LS-infected hepatocytes from the rodent host. Genome-wide LS gene expression was profiled and compared with other parasite life cycle stages. The analysis revealed ≈ 2,000 genes active during LS development, and proteomic analysis identified 816 proteins. A subset of proteins appeared to be expressed in LS only. The data revealed exported parasite proteins and LS metabolic pathways including expression of FASII pathway enzymes. The FASII inhibitor hexachlorophene and the antibiotics, tetracycline and rifampicin, that target the apicoplast inhibited LS development, identifying FASII and other pathways localized in the apicoplast as potential drug targets to prevent malaria infection.
机译：自发现疟疾以来的50年中，疟疾寄生虫肝阶段（LS）一直难以分析，从而阻碍了其作为抗感染疫苗和药物的重要靶标的利用。我们已结合LS的蛋白质组学研究进行了全面的转录组分析。用绿色荧光蛋白标记的约氏疟原虫（PyGFP）从啮齿动物宿主中有效分离出LS感染的肝细胞。全基因组LS基因表达谱进行了分析，并与其他寄生虫生命周期阶段进行了比较。该分析揭示了大约2,000个在LS发育过程中活跃的基因，而蛋白质组学分析则鉴定出816个蛋白质。一部分蛋白质似乎仅在LS中表达。数据揭示了输出的寄生虫蛋白和LS代谢途径，包括FASII途径酶的表达。 FASII抑制剂六氯芬和靶向蜂胶体的抗生素四环素和利福平抑制了LS的发展，确定了FASII和位于蜂胶体中的其他途径是预防疟疾感染的潜在药物靶标。

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