Host biotin is required for liver stage development in malaria parasites.
Host biotin is required for liver stage development in malaria parasites.
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DOI：
10.1073/pnas.1800717115
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发表时间：
2018-03-13
影响因子：
11.1
通讯作者：
Prigge ST
中科院分区：
文献类型：
--
作者：
Dellibovi-Ragheb TA;Jhun H;Goodman CD;Walters MS;Ragheb DRT;Matthews KA;Rajaram K;Mishra S;McFadden GI;Sinnis P;Prigge ST
疟疾寄生虫需要一定的宿主营养才能生长和生存。在这个项目中，我们研究了人类维生素生物素在疟疾生命周期的所有阶段中的作用。我们在没有生物素的情况下培养了血液和肝脏阶段的疟疾寄生虫，发现虽然血液阶段的复制没有受到影响，但失去生物素的肝脏阶段的寄生虫不再能够确定血液阶段的感染。有趣的是，生物素枯竭导致的发育缺陷比寄生虫生物素代谢的遗传障碍更严重。这一发现表明，宿主生物素代谢也有助于寄生虫的发育。由于寄生虫和人类宿主都不能合成生物素，因此寄生虫的传染性可能会受到宿主营养状况的影响。乙酰辅酶A羧化酶(ACC)是一种依赖生物素的酶，是几类除草剂的靶标。疟疾寄生虫含有一种类似植物的ACC，这是唯一被预测在寄生虫中被生物素化的蛋白质。我们发现ACC在肝期和血期疟原虫的顶生质膜细胞器中表达；然而，它只在肝期通过生物素活化而激活。与此观察一致的是，负责ACC生物素化的生物素连接酶的缺失不会阻碍血液阶段的生长，但会导致肝脏晚期发育缺陷。生物素缺乏增加了发育缺陷的严重程度，表明寄生虫和宿主生物素代谢是正常肝脏阶段进展所必需的。这一发现可能将肝期疟疾寄生虫的发展与宿主的营养状况联系起来，因为寄生虫和人类宿主都不能合成生物素。
Malaria parasites require certain host nutrients for growth and survival. In this project, we examined the role of the human vitamin biotin in all stages of the malaria life cycle. We cultured blood- and liver-stage malaria parasites in the absence of biotin and found that, whereas blood-stage replication was unaffected, liver-stage parasites deprived of biotin were no longer capable of establishing a blood-stage infection. Interestingly, biotin depletion resulted in more severe developmental defects than the genetic disruption of parasite biotin metabolism. This finding suggests that host biotin metabolism also contributes to parasite development. Because neither the parasite nor the human host can synthesize biotin, parasite infectivity may be affected by the nutritional status of the host. Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin.
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影响因子：
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作者：
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通讯作者：
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Prigge ST
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3.4
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