Elucidation of the molecular cleavage mechanism of malaria parasite sporozoite tropism by Plasmepsin IX

Human infection with the malaria parasite occurs when the infectious form (sporozoites) accumulated in the salivary glands of the vector mosquito is injected into the human skin during blood-feeding, infecting liver cells. Therefore, understanding malaria transmission is crucial. When sporozoites invade cells, several important proteins are secreted from the pterygium, the organelle at the tip of the sporozoite, and many of these undergo complex processing. However, the mechanisms and their impact on sporozoite infection dynamics remain unclear. This study aims to clarify the mechanism and biological significance of sporozoite processing of pterygium proteins by the pterygium-localized protease, Plasmepsin IX (PMIX).
In the previously created sporozoite-temporal PMIX knockdown parasite (PMIX-cKD), the number of sporozoites in the midgut and body fluids was similar to that of the control, but the number of salivary gland sporozoites was reduced to about 1/100th of that of the control. To determine whether PMIX is involved in the invasion of sporozoites into hepatocytes, we compared the intracellular and extracellular sporozoite counts one hour after seeding PMIX-cKD and control protozoa derived from body fluids into cultured hepatocytes (HepG2). In PMIX-cKD, the number of intracellular sporozoites decreased to 1/50th of that of the control. These findings indicate that suppression of PMIX expression affects invasion into salivary glands and hepatocytes. To analyze PMIX expression in sporozoites, rabbits were immunized with recombinant PMIX protein and performed IFA and Western blot using the resulting antiserum, but a PMIX-specific signal was not obtained. This project is currently developing a new antibody and analyzing the mRNA expression patterns of midgut oocysts collected over time to understand the dynamics of PMIX expression in sporozoites.

Project details

Basic Science

Apr 2024 — Mar 2027

$30,900

Japan