モリタ　マサユキ   Masayuki Morita   森田　将之    所属   川崎医科大学  医学部 基礎医学　解剖学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Plasmodium falciparum Liver Stage Antigen 3 plays a role in completing the final stages of merozoite invasion of red blood cells.
掲載誌名	正式名：International journal for parasitology 略　 称：Int J Parasitol ISSNコード：18790135/00207519
掲載区分	国外
巻・号・頁	56(5),pp.104743
著者・共著者	Masayuki Morita, Charlie Jennison, Matthew T O'Neill, Bernard N Kanoi, Tomoko Ishino, Takafumi Tsuboi, Justin A Boddey, Eizo Takashima
担当区分	筆頭著者,責任著者
発行年月	2026/05
概要	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.
DOI	10.1016/j.ijpara.2025.10.003
PMID	41135800