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

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

  • Int J Parasitol Drugs Drug Resist. 2024 Aug 14:26:100563. doi: 10.1016/j.ijpddr.2024.100563.
Xitong Jia 1,  Yong Wang 2,  Meilian Wang 3,  Hui Min 4,  Zehou Fang 5,  Haifeng Lu 3,  Jiao Li 3,  Yaming Cao 6,  Lunhao Bai 7,  Jinghan Lu 8
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, 110000, China; Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110122, China.
  • 2 Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110122, China; Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, 110000, China.
  • 3 Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110122, China.
  • 4 Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110122, China.
  • 5 The Second Clinical College of China Medical University, Shenyang, Liaoning, 110122, China.
  • 6 Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, 110122, China. Electronic address: ymcao@cmu.edu.cn.
  • 7 Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, 110000, China. Electronic address: bailh@sj-hospital.org.
  • 8 Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, 110000, China. Electronic address: lujh1@sj-hospital.org.
PMID: 39153438 DOI: 10.1016/j.ijpddr.2024.100563
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.

Keywords

Malaria; Phosphatase inhibitor; Plasmodium berghei; Transmission.

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