Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany.
Division of Enteropathogenic Bacteria and Legionella, Robert Koch- Institute, Burgstraße 37, 38855 Wernigerode, Germany.
Int J Med Microbiol. 2018 Jan;308(1):129-141. doi: 10.1016/j.ijmm.2017.09.015. Epub 2017 Sep 23.
Plasmodium parasites, the causative agents of malaria, display a well-regulated lipid metabolism required to ensure their survival in the human host as well as in the mosquito vector. The fine-tuning of lipid metabolic pathways is particularly important for the parasites during the rapid erythrocytic infection cycles, and thus enzymes involved in lipid metabolic processes represent prime targets for malaria chemotherapeutics. While plasmodial enzymes involved in lipid synthesis and acquisition have been studied in the past, to date not much is known about the roles of phospholipases for proliferation and transmission of the malaria parasite. These phospholipid-hydrolyzing esterases are crucial for membrane dynamics during host cell infection and egress by the parasite as well as for replication and cell signaling, and thus they are considered important virulence factors. In this review, we provide a comprehensive bioinformatic analysis of plasmodial phospholipases identified to date. We further summarize previous findings on the lipid metabolism of Plasmodium, highlight the roles of phospholipases during parasite life-cycle progression, and discuss the plasmodial phospholipases as potential targets for malaria therapy.
疟原虫寄生虫是疟疾的病原体,它们在人类宿主和蚊子媒介中生存需要进行良好调节的脂质代谢。脂质代谢途径的微调对于寄生虫在快速的红细胞感染周期中尤为重要,因此参与脂质代谢过程的酶是疟疾化疗的主要靶点。虽然过去已经研究了参与脂质合成和获取的疟原虫酶,但迄今为止,对于磷脂酶在疟原虫的增殖和传播中的作用知之甚少。这些磷脂水解酶对于寄生虫感染宿主细胞和逸出、复制和细胞信号转导过程中的膜动力学至关重要,因此被认为是重要的毒力因子。在这篇综述中,我们对迄今为止鉴定的疟原虫磷脂酶进行了全面的生物信息学分析。我们进一步总结了以前关于疟原虫脂质代谢的发现,强调了磷脂酶在寄生虫生命周期进展中的作用,并讨论了疟原虫磷脂酶作为疟疾治疗的潜在靶点。