Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria
Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria
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DOI：
10.1038/s41598-018-37816-9
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发表时间：
2019-02-27
影响因子：
4.6
通讯作者：
Langsley, Gordon
中科院分区：
文献类型：
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作者：
Beri, Divya;Ramdani, Ghania;Langsley, Gordon
疟原虫sp.是专性的细胞内寄生虫，它们的大部分营养来自宿主，这意味着两者的新陈代谢电路错综复杂地联系在一起。我们使用无针对性的全球质谱仪来鉴定恶性疟原虫感染红细胞的培养上清液中存在的代谢物，这些红细胞在环状、滋养体和裂殖体发育阶段同步。这揭示了与未感染的红细胞上清液相比，一组不同的代谢物的释放具有时间规律性。在不同的代谢物中，我们发现在寄生虫的裂解物、感染的红细胞和感染的培养上清液中都含有丰富的吡哌酸。此外，我们还进行了靶向代谢组学研究，以量化恶性疟原虫感染小鼠的红细胞上清液以及伯氏疟原虫感染小鼠的血浆和感染红细胞中的吡哌酸浓度。可测量和显著的高管性血症表明，吡哌酸有可能成为疟疾的诊断标记物。
Plasmodium sp. are obligate intracellular parasites that derive most of their nutrients from their host meaning the metabolic circuitry of both are intricately linked. We employed untargeted, global mass spectrometry to identify metabolites present in the culture supernatants of P. falciparum-infected red blood cells synchronized at ring, trophozoite and schizont developmental stages. This revealed a temporal regulation in release of a distinct set of metabolites compared with supernatants of noninfected red blood cells. Of the distinct metabolites we identified pipecolic acid to be abundantly present in parasite lysate, infected red blood cells and infected culture supernatant. Further, we performed targeted metabolomics to quantify pipecolic acid concentrations in both the supernatants of red blood cells infected with P. falciparum, as well as in the plasma and infected RBCs of P. berghei-infected mice. Measurable and significant hyperpipecolatemia suggest that pipecolic acid has the potential to be a diagnostic marker for malaria.