Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria
Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria
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DOI：
10.1016/j.ijmm.2017.09.002
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发表时间：
2017-12-01
影响因子：
4.1
通讯作者：
Li, Shuzhao
中科院分区：
文献类型：
--
作者：
Gardinassi, Luiz Gustavo;Cordy, Regina Joice;Li, Shuzhao
背景：间日疟原虫是世界范围内引起疟疾的主要原因之一。感染这种寄生虫会引起不同的临床表现，最近的研究表明，感染间日疟原虫可导致严重和致命的疾病。尽管有这些事实，间日疟期间宿主反应和寄生虫新陈代谢的生物学特征仍在很大程度上未得到充分研究。寄生虫血症与恶性疟原虫引起的疟疾的进展和严重程度明显相关，但对间日疟原虫感染过程中寄生虫血症的影响尚不清楚。结果：我们利用高分辨率代谢组学平台进行了一项探索性研究，发现150例间日疟患者的寄生虫血症水平与血浆代谢物之间存在显著关联。大多数血浆代谢物与较高水平的寄生虫血症呈负相关。预测的主要代谢产物包括胆绿素、胆红素、棕榈酰卡尼汀、硬脂酰卡尼汀、磷胆碱、甘油磷胆碱、油酸和欧米伽-羧基-三或-白三烯B4。结论：间日疟原虫血症患者血浆中多种代谢物的丰度随寄生虫血症程度的不同而变化。此外，我们的数据表明，宿主的反应和/或寄生虫的生存可能受到参与血红素降解和几种脂类代谢的代谢物的影响。重要的是，这些数据突出了可以作为新抗疟疾化合物开发目标的代谢途径。
Background: Plasmodium vivax is one of the leading causes of malaria worldwide. Infections with this parasite cause diverse clinical manifestations, and recent studies revealed that infections with P. vivax can result in severe and fatal disease. Despite these facts, biological traits of the host response and parasite metabolism during P. vivax malaria are still largely underexplored. Parasitemia is clearly related to progression and severity of malaria caused by P. falciparum, however the effects of parasitemia during infections with P. vivax are not well understood.Results: We conducted an exploratory study using a high-resolution metabolomics platform that uncovered significant associations between parasitemia levels and plasma metabolites from 150 patients with P. vivax malaria. Most plasma metabolites were inversely associated with higher levels of parasitemia. Top predicted metabolites are implicated into pathways of heme and lipid metabolism, which include biliverdin, bilirubin, palmitoylcarnitine, stearoylcarnitine, phosphocholine, glycerophosphocholine, oleic acid and omega-carboxy-trinor-leukotriene B4.Conclusions: The abundance of several plasma metabolites varies according to the levels of parasitemia in patients with P. vivax malaria. Moreover, our data suggest that the host response and/or parasite survival might be affected by metabolites involved in the degradation of heme and metabolism of several lipids. Importantly, these data highlight metabolic pathways that may serve as targets for the development of new antimalarial compounds.