The C-terminal region of the Plasmodium berghei gamete surface 184-kDa protein Pb184 contributes to fertilization and male gamete binding to the residual body

TL;DR

Researchers found that a protein in malaria parasites, Pb184, plays a role in fertilization and could help prevent malaria transmission.

Contribution

The study identifies the C-terminal region of Pb184 as critical for gamete binding and fertilization in Plasmodium berghei.

Findings

Pb184 is expressed on the surface of male and female gametes and is involved in fertilization.

Antibodies and peptides targeting Pb184 inhibit zygote and ookinete formation in vitro.

Pb184 peptides bind to the residual body of male gametes and inhibit ookinete differentiation.

Abstract

Malaria, a global health concern, is caused by parasites of the Plasmodium genus, which undergo gametogenesis in the midgut of mosquitoes after ingestion of an infected blood meal. The resulting male and female gametes fuse to form a zygote, which differentiates into a motile ookinete. After traversing the midgut epithelium, the ookinete differentiates into an oocyst on the basal side of the epithelium.

Membrane proteins with increased gene expression levels from the gamete to oocyst stages in P. berghei were investigated utilizing PlasmoDB, the functional genomic database for Plasmodium spp. Based on this analysis, we selected the 184-kDa membrane protein, Pb184, for further study. The expression of Pb184 was further confirmed through immunofluorescence staining, following which we examined whether Pb184 is involved in fertilization using antibodies targeting the C-terminal region of Pb184 and biotin-labeled C-terminal region peptides of Pb184.

Pb184 is expressed on the surface of male and female gametes. The antibody inhibited zygote and ookinete formation in vitro. When mosquitoes were fed on parasite-infected blood containing the antibody, oocyst formation decreased on the second day after feeding. Synthesized biotin-labeled peptides matching the C-terminal region of Pb184 bound to the female gamete and the residual body of male gametes, and inhibited differentiation into ookinetes in the in vitro culture system.

These results may be useful for the further studying the fertilization mechanism of Plasmodium protozoa. There is also the potential for their application as future tools to prevent malaria transmission.

The online version contains supplementary material available at 10.1186/s13071-024-06374-7.

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