Plasmodium GPI-anchored micronemal antigen is essential for parasite transmission through the mosquito host.
Plasmodium parasites, the eukaryotic pathogens that cause malaria, feature three distinct invasive forms tailored to the host environment they must navigate and invade for life cycle progression. One conserved feature of these invasive forms is the micronemes, apically oriented secretory organelles involved in egress, motility, adhesion, and invasion. Here we investigate the role of GPI-anchored micronemal antigen (GAMA), which shows a micronemal localization in all zoite forms of the rodent-infecting species Plasmodium berghei. ∆GAMA parasites are severely defective for invasion of the mosquito midgut. Once formed, oocysts develop normally, however, sporozoites are unable to egress and exhibit defective motility. Epitope-tagging of GAMA revealed tight temporal expression late during sporogony and showed that GAMA is shed during sporozoite gliding motility in a similar manner to circumsporozoite protein. Complementation of P. berghei knockout parasites with full-length P. falciparum GAMA partially restored infectivity to mosquitoes, indicating conservation of function across Plasmodium species. A suite of parasites with GAMA expressed under the promoters of CTRP, CAP380, and TRAP, further confirmed the involvement of GAMA in midgut infection, motility, and vertebrate infection. These data show GAMA's involvement in sporozoite motility, egress, and invasion, implicating GAMA as a regulator of microneme function.
Institute for Systems Biology
Jennison, Charlie; Armstrong, Janna M; Dankwa, Dorender A; Hertoghs, Nina; Kumar, Sudhir; Abatiyow, Biley A; Naung, Myo; Minkah, Nana K; Swearingen, Kristian E; Moritz, Robert; Barry, Alyssa E; Kappe, Stefan H I; and Vaughan, Ashley M, "Plasmodium GPI-anchored micronemal antigen is essential for parasite transmission through the mosquito host." (2023). Articles, Abstracts, and Reports. 7485.