Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum.
Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum.
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DOI：
10.1016/j.chom.2015.08.003
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发表时间：
2015-09-09
影响因子：
30.3
通讯作者：
Fidock DA
中科院分区：
文献类型：
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作者：
Gulati S;Ekland EH;Ruggles KV;Chan RB;Jayabalasingham B;Zhou B;Mantel PY;Lee MC;Spottiswoode N;Coburn-Flynn O;Hjelmqvist D;Worgall TS;Marti M;Di Paolo G;Fidock DA
在其生命周期中，恶性疟原虫经历了由从头合成和获得宿主细胞脂质所推动的快速增殖。与这一重要作用相一致，疟原虫脂质合成酶正在成为潜在的药物靶点。为了探索其更广泛的治疗干预潜力，我们分析了恶性疟原虫无性血液阶段（ABS）和性发育期间的整体脂质景观。使用液相色谱-质谱法，我们分析了304脂质构成24类ABS寄生虫，感染的红细胞（RBC）衍生的微泡，配子体，和未感染的红细胞。恶性疟原虫中有10种脂质类以前未被表征，70-75%的脂质类在ABS和配子体发育期间表现出丰度的变化。利用靶向脂质代谢的化合物，我们肯定了包括三酰甘油在内的主要类别的重要性。这些研究突出了宿主和寄生虫脂质代谢之间的相互作用，并提供了一个全面的分析恶性疟原虫脂质与药物发现工作的候选途径。
During its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium lipid synthesis enzymes are emerging as potential drug targets. To explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during P. falciparum asexual blood stage (ABS) and sexual development. Using liquid chromatography–mass spectrometry, we analyzed 304 lipids constituting 24 classes in ABS parasites, infected red blood cell (RBC)-derived microvesicles, gametocytes, and uninfected RBCs. Ten lipid classes were previously uncharacterized in P. falciparum and 70–75% of the lipid classes exhibited changes in abundance during ABS and gametocyte development. Utilizing compounds that target lipid metabolism, we affirmed the essentiality of major classes, including triacylglycerols. These studies highlight the interplay between host and parasite lipid metabolism and provide a comprehensive analysis of P. falciparum lipids with candidate pathways for drug discovery efforts.