A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission

Abstract

Mosquito midgut epithelium traversal is essential for malaria parasite transmission. Phospholipid flippases are eukaryotic type 4 P-type adenosine triphosphatases (P4-ATPases), which, in association with CDC50, translocate phospholipids across the membrane lipid bilayers. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite Plasmodium yoelii. Disruption of ATP7 blocks the parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are capable of invading the midgut, they are eliminated within the epithelial cells by a process independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase cofactor CDC50C. Depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to uptake phosphatidylcholine across the plasma membrane. Ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies Plasmodium flippase as a mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.

Searching for new molecules involved in <i>Anopheles</i> mosquitoes’ response to <i>Plasmodium</i> infection

“…This is the first study to examine gene expression in female and male mosquitoes injected with Plasmodium parasites. Previous studies have primarily focused on bypassing midgut transit during infection by injection, and there have been no reports analyzing the molecular changes in the injected mosquitoes [ 4 , 8 , 10 , 11 , 20 ]. The RNA-seq data obtained from this study will provide valuable information on the interaction between Plasmodium parasites and mosquitoes.…”

CDC50 Orthologues in Plasmodium falciparum Have Distinct Roles in Merozoite Egress and Trophozoite Maturation

“…A recent study in P. yoelii has shown that the orthologue of CDC50C binds to a different P4-ATPase (ATP7) in ookinetes during parasite development within the mosquito ( 54 ). This indicates that CDC50C chaperones the activity of distinct P4-ATPases in different developmental stages of the parasite life cycle in both mammalian and insect hosts.…”

The flexibility of Apicomplexa parasites in lipid metabolism

“…exist but without confirmation of function. Recently, the Plasmodium yoelii ATP7 ATPase has been characterized as a phospholipid transporter responsible for the uptake of PC across the plasma membrane in mosquito stage ookinetes [ 83 ]. Both Toxoplasma and Plasmodium sp.…”