Plasmodium female gamete surface HSP90 is a key determinant for fertilization

• Published in: mBio Vol. 15; no. 2; p. e0314223
• Main Authors: Cha, Sung-Jae, Vega-Rodriguez, Joel, Tao, Dingyin, Kudyba, Heather M, Hanner, Kelly, Jacobs-Lorena, Marcelo
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 14.02.2024
• Subjects: Animals; Culicidae - parasitology; Female; Fertilization; Germ Cells - metabolism; HSP90; Humans; Male; male binding peptide; Parasitology; Peptides; phage display; Plasmodium; Plasmodium falciparum - metabolism; Plasmodium fertilization; Protozoan Proteins - metabolism; Research Article; transmission blocking; Vaccines; HSP90; transmission blocking; male binding peptide; Plasmodium fertilization; phage display
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.03142-23

fertilization, an essential step for the development of the malaria parasite in the mosquito, is a prime target for blocking pathogen transmission. Using phage peptide display screening, we identified MG1, a peptide that binds to male gametes and inhibits fertilization, presumably by competing with a female gamete ligand. Anti-MG1 antibodies bind to the female gamete surface and, by doing so, also inhibit fertilization. We determined that this antibody recognizes HSP90 on the surface of female gametes. Our findings establish HSP90 as a prime target for the development of a transmission-blocking vaccine.IMPORTANCEMalaria kills over half a million people every year and this number has not decreased in recent years. The development of new tools to combat this disease is urgently needed. In this article, we report the identification of a key molecule-HSP90-on the surface of the parasite's female gamete that is required for fertilization to occur and for the completion of the parasite cycle in the mosquito. HSP90 is a promising candidate for the development of a transmission-blocking vaccine.