2023 Fiscal Year Final Research Report
Investigation of the molecular mechanism of RON4 in Plasmodium berghei sporozoite infection of mammalian hosts
| Project/Area Number |
20K16235
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | Tokyo Medical and Dental University (2023)
Nagasaki University (2021-2022)
Ehime University (2020) |
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Principal Investigator |
Baba Minami 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (00814906)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | マラリア / RON4 / rhoptry neck protein / liver stage / sporozoite / Plasmodium / スポロゾイト / 細胞侵入 |
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| Outline of Final Research Achievements |
Rhoptry neck protein 4 (RON4) is one of rhoptry proteins which are conserved between infective stages, merozoite and sporozoite. The attempts to generate RON4 knockout parasites have failed possibly due to its essentiality for parasite proliferation during the blood stage. Therefore, until now, the function of RON4 in sporozoites remains unelucidated.
To elucidate RON4 function during the sporozoite stage, we applied the sporozoite stage-specific knockdown system by promoter swapping in the rodent malaria parasite strain, Plasmodium berghei. RON4-cKD sporozoites suppressed invasion of mosquito salivary glands. In addition, cell traversal and infection of hepatocytes were also inhibited in RON4-cKD parasites. In RON4-cKD sporozoites, attachment and motility, which are important for these steps, were suppressed, suggesting that RON4 is involved in salivary gland invasion and liver infection by mediating the attachment and motility of sporozoites.
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| Free Research Field |
寄生虫学
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| Academic Significance and Societal Importance of the Research Achievements |
スポロゾイトが有しているロプトリーの分子の多くは、もう一つの感染型であるメロゾイトで必須であるためにノックアウト原虫の作出ができず、逆遺伝学手法による機能解析が困難であった。本研究では、RON4をプロモーター置換法を用いてスポロゾイト時期特異的に発現抑制することで、スポロゾイトにおけるRON4の機能解析を可能にした。本研究課題ではスポロゾイトは移動中にRON4を分泌し、分泌されたRON4が肝細胞への感染に役割を有することを示唆する結果を得た。このことからRON4がスポロゾイト期を標的とした新たなワクチン候補となりうると考えられる。
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