Published: June 14, 2023
Jennison C, Armstrong JM, Dankwa DA, Hertoghs N, Kumar S, Abatiyow BA, Naung M, Minkah NK, Swearingen KE, Moritz R, Barry AE, Kappe SHI, Vaughan AM. Plasmodium GPI-anchored micronemal antigen is essential for parasite transmission through the mosquito host. Mol Microbiol. 2023 Jun 14. doi: 10.1111/mmi.15078. Epub ahead of print. PMID: 37314965.
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.