A Novel Plasmodium berghei Protein, LSMP, Regulates Malaria Liver Stage Maturation.

Abstract

Malaria parasites undergo extensive replication in hepatocytes before initiating the pathogenic blood stage of infection. Although this clinically silent phase is essential for parasite expansion, the molecular mechanisms regulating late liver stage maturation remain incompletely understood. Here, we characterize a previously unannotated protein (PBANKA_0620800), which we designate liver stage maturation protein (LSMP). LSMP was expressed during schizont, sporozoite, and liver stages and localized predominantly to the parasite cytosol. Using reverse genetic approaches, we generated LSMP KO parasites and examined their development across the parasite life cycle. Loss of LSMP did not affect asexual blood-stage replication or mosquito-stage development, including ookinete formation, oocyst development, and sporozoite formation. LSMP KO sporozoites invaded hepatocytes normally but exhibited pronounced defects during late liver stage development, including reduced nuclear replication, impaired merozoite formation, and delayed rupture of the parasitophorous vacuole membrane. Together, our findings demonstrate that LSMP is important for malaria liver stage maturation.