ApicoLipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble Alpes, INSERM U1209, Grenoble, France.
Methods Mol Biol. 2024;2776:197-204. doi: 10.1007/978-1-0716-3726-5_12.
Apicomplexan parasites are unicellular eukaryotes responsible for major human diseases such as malaria and toxoplasmosis, which cause massive social and economic burden. Toxoplasmosis, caused by Toxoplasma gondii, is a global chronic infectious disease affecting ~1/3 of the world population and is a major threat for any immunocompromised patient. To date, there is no efficient vaccine against these parasites and existing treatments are threatened by rapid emergence of parasite resistance. Throughout their life cycle, Apicomplexa require large amount of nutrients, especially lipids for propagation and survival. Understanding lipid acquisition is key to decipher host-parasite metabolic interactions. Parasite membrane biogenesis relies on a combination of (a) host lipid scavenging, (b) de novo lipid synthesis in the parasite, and (c) fluxes of lipids between host and parasite and within. We recently uncovered that parasite need to store the host-scavenged lipids to avoid their toxic accumulation and to mobilize them for division. How can parasites orchestrate the many lipids fluxes essential for survival? Here, we developed metabolomics approaches coupled to stable isotope labelling to track, monitor, and quantify fatty acid and lipids fluxes between the parasite, its human host cell, and its extracellular environment to unravel the complex lipid fluxes in any physiological environment the parasite could meet.
顶复门寄生虫是单细胞真核生物,可导致疟疾和弓形体病等主要人类疾病,给社会和经济带来巨大负担。弓形体病由刚地弓形虫引起,是一种全球性慢性传染病,影响全球约三分之一的人口,对任何免疫功能低下的患者都是重大威胁。迄今为止,尚无针对这些寄生虫的有效疫苗,而现有的治疗方法也受到寄生虫耐药性迅速出现的威胁。在整个生命周期中,顶复门寄生虫需要大量的营养物质,尤其是脂质来繁殖和生存。了解脂质的获取方式是破解宿主-寄生虫代谢相互作用的关键。寄生虫膜的生物发生依赖于以下三种方式的结合:(a)宿主脂质的掠夺,(b)寄生虫内从头合成脂质,以及(c)宿主与寄生虫之间以及寄生虫内的脂质流动。我们最近发现,寄生虫需要储存掠夺的宿主脂质,以避免其毒性积累,并为分裂调动这些脂质。寄生虫如何协调生存所需的多种脂质流动?在这里,我们开发了代谢组学方法,并结合稳定同位素标记,以追踪、监测和量化寄生虫与其人类宿主细胞及其细胞外环境之间的脂肪酸和脂质流动,以揭示寄生虫在任何生理环境中复杂的脂质流动。