Plasmodium GPI-Anchored Micronemal Antigen is essential for parasite transmission through the mosquito host [article]

Charlie Jennison, Janna M. Gibson, Nina Hertoghs, Dorender A. Dankwa, Sudhir Kumar, Biley A. Abatiyow, Myo Naung, Nana K. Minkah, Kristian E. Swearingen, Robert L Moritz, Alyssa. E. Barry, Stefan H. I. Kappe (+1 others)
2022 bioRxiv   pre-print
The complex life cycle of Plasmodium parasites, the eukaryotic pathogens that cause malaria, features three distinct invasive forms tailored specifically to the equally distinct host environment they must navigate and invade for progression of the life cycle. One conserved feature of all these invasive forms is the presence of micronemes, apically oriented secretory organelles involved in egress, motility, adhesion and invasion. Micronemes are tailored to their specific host environment and
more » ... ure stage specific contents. 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. While GAMA is dispensable during asexual blood stages, GAMA knock out parasites are severely defective for invasion of the mosquito midgut, resulting in reduced numbers of oocysts. Once formed, oocysts develop normally, however sporozoites are unable to egress and these sporozoites 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 knock out parasites with full length P. falciparum GAMA partially restored infectivity to mosquitoes, indicating a conservation of function across Plasmodium species. A suite of parasites with GAMA expressed under the promoters of the known ookinete-tosporozoite stage-specific genes: CTRP, CAP380 and TRAP, further confirmed the involvement of GAMA in midgut infection, motility and infection of the mammalian host and revealed a lethal consequence to overexpression of GAMA during oocyst development. Combined, the research suggest that GAMA plays independent roles in sporozoite motility, egress and invasion, possibly implicating GAMA as a regulator of microneme function.
doi:10.1101/2022.02.24.481744 fatcat:jj6lu5sfbbcgvb5kgud3ctk3s4