Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.
Inserm U1016, Cnrs UMR8104, Cochin Institute, Paris, 75014, France.
Sci Rep. 2019 Feb 27;9(1):2875. doi: 10.1038/s41598-018-37816-9.
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 non-infected 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.
疟原虫是专性细胞内寄生虫，它们的大部分营养物质来自宿主，这意味着它们的代谢途径是紧密相连的。我们采用非靶向、全局质谱法来鉴定处于环状体、滋养体和裂殖体发育阶段的疟原虫感染红细胞培养上清液中的代谢物。与未感染的红细胞上清液相比，这揭示了在释放一组独特的代谢物方面存在时间调节。在我们鉴定出的独特代谢物中，哌可酸在寄生虫裂解物、感染的红细胞和感染的培养上清液中大量存在。此外，我们还进行了靶向代谢组学分析，以定量检测疟原虫感染的红细胞上清液以及伯氏疟原虫感染的小鼠血浆和感染的 RBC 中的哌可酸浓度。可测量和显著的高哌可酸血症表明，哌可酸有可能成为疟疾的诊断标志物。
