The phosphatase inhibitor BVT-948 can be used to efficiently screen functional sexual development proteins in the malaria parasite Plasmodium berghei

Xitong Jia , Yong Wang , Meilian Wang , Hui Min , Zehou Fang , Haifeng Lu , Jiao Li , Yaming Cao , Lunhao Bai , Jinghan Lu
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Abstract

Background

Studying and discovering the molecular mechanism of Plasmodium sexual development is crucial for the development of transmission blocking drugs and malaria eradication. The aim of this study was to investigate the feasibility of using phosphatase inhibitors as a tool for screening proteins essential for Plasmodium sexual development and to discover proteins affecting the sexual development of malaria parasites.

Methods

Differences in protein phosphorylation among Plasmodium gametocytes incubated with BVT-948 under in vitro ookinete culture conditions were evaluated using phosphoproteomic methods. Gene Ontology (GO) analysis was performed to predict the mechanism by which BVT-948 affected gametocyte–ookinete conversion. The functions of 8 putative proteins involved in Plasmodium berghei sexual development were evaluated. Bioinformatic analysis was used to evaluate the possible mechanism of PBANKA_0100800 in gametogenesis and subsequent sexual development.

Results

The phosphorylation levels of 265 proteins decreased while those of 67 increased after treatment with BVT-948. Seven of the 8 genes selected for phenotype screening play roles in P. berghei sexual development, and 4 of these were associated with gametocytogenesis. PBANKA_0100800 plays essential roles in gametocyte–ookinete conversion and transmission to mosquitoes.

Conclusions

Seven proteins identified by screening affect P. berghei sexual development, suggesting that phosphatase inhibitors can be used for functional protein screening.

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磷酸酶抑制剂 BVT-948 可用于有效筛选疟原虫中的功能性性发育蛋白。
背景:研究和发现疟原虫性发育的分子机制对于开发传播阻断药物和根除疟疾至关重要。本研究旨在探讨使用磷酸酶抑制剂作为筛选疟原虫性发育必需蛋白的工具的可行性,并发现影响疟原虫性发育的蛋白:方法:在体外卵母细胞培养条件下,使用BVT-948培养的疟原虫配子细胞之间的蛋白质磷酸化差异通过磷酸蛋白组学方法进行了评估。通过基因本体(GO)分析预测了BVT-948影响配子细胞-卵母细胞转化的机制。对参与疟原虫性发育的 8 种推测蛋白的功能进行了评估。利用生物信息学分析评估了PBANKA_0100800在配子发生和随后的性发育过程中的可能机制:结果:经 BVT-948 处理后,265 个蛋白质的磷酸化水平降低,67 个蛋白质的磷酸化水平升高。表型筛选出的 8 个基因中有 7 个在伯格氏疟原虫性发育过程中发挥作用,其中 4 个与配子细胞发生有关。PBANKA_0100800 在配子-卵子转换和传播给蚊子的过程中起着至关重要的作用:结论:通过筛选确定的 7 个蛋白质影响伯格氏疟原虫的性发育,表明磷酸酶抑制剂可用于功能蛋白质筛选。
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来源期刊
CiteScore
7.90
自引率
7.50%
发文量
31
审稿时长
48 days
期刊介绍: The International Journal for Parasitology – Drugs and Drug Resistance is one of a series of specialist, open access journals launched by the International Journal for Parasitology. It publishes the results of original research in the area of anti-parasite drug identification, development and evaluation, and parasite drug resistance. The journal also covers research into natural products as anti-parasitic agents, and bioactive parasite products. Studies can be aimed at unicellular or multicellular parasites of human or veterinary importance.
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