Plasmodium falciparum Liver Stage Antigen 3 plays a role in completing the final stages of merozoite invasion of red blood cells
- Author(s)
- Morita, M; Jennison, C; O'Neill, MT; Kanoi, BN; Ishino, T; Tsuboi, T; Boddey, JA; Takashima, E;
- Journal Title
- International Journal for Parasitology
- Publication Type
- Oct 27
- Abstract
- Understanding the red blood cell (RBC) invasion mechanism by Plasmodium falciparum, the causative agent of human malaria, is critical for developing blood-stage vaccines. Most research on the roles of parasite molecules during invasion into the RBC has focused on the pre-invasion and invasion phases, particularly on merozoite proteins in these early steps. Consequently, well-established blood-stage vaccine candidates, such as MSP1, AMA1, EBA175, Rh5, CyRPA, and Ripr, have been discovered by research targeting the early invasion phases. Recently, we identified that Liver Stage Antigen 3 (LSA3) is a merozoite dense granule protein and a novel blood-stage vaccine candidate, given that antigen-specific antibodies inhibit parasite growth by 24%. However, the precise role of LSA3 in RBC invasion remains unclear. In this study, we investigated the function of LSA3 during merozoite invasion of RBCs. In the late-invasion phase, LSA3 localized to the posterior end of invading wild-type merozoites accessible to anti-LSA3 antibodies in the culture medium. In vitro cultured lsa3 knockout parasites (ΔLSA3) exhibited slowed parasite growth. Time-lapse imaging revealed that knockout of lsa3 resulted in a 65% reduction in normal invasion completion relative to the wild-type. Furthermore, ΔLSA3 parasites displayed a high frequency of accolé-form: aberrant morphology, with a protruding convex-shaped ring-stage just beneath the RBC membrane, following successful internalization into RBCs. This study provides the first evidence that a merozoite dense granule protein potentially plays an important role in the late-invasion phase of the P. falciparum erythrocytic cycle.
- Publisher
- Elsevier
- Keywords
- Dense granule; Lsa3; Malaria; Merozoite invasion; Plasmodium falciparum
- Research Division(s)
- Infection and Global Health
- PubMed ID
- 41135800
- Publisher's Version
- https://doi.org/10.1016/j.ijpara.2025.10.003
- Open Access at Publisher's Site
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Creation Date: 2025-11-03 09:22:05
Last Modified: 2025-11-11 11:22:14