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博士論文 / Critical role of Erythrocyte Binding-Like protein of the rodent malaria parasite Plasmodium yoelii to establish an irreversible connection with the erythrocyte during invasion ネズミマラリア原虫Plasmodium yoeliiのErythrocyte Binding-Likeタンパク質は赤血球侵入過程における不可逆的結合形成に重要である

著者

書誌事項

タイトル

Critical role of Erythrocyte Binding-Like protein of the rodent malaria parasite Plasmodium yoelii to establish an irreversible connection with the erythrocyte during invasion

タイトル別名

ネズミマラリア原虫Plasmodium yoeliiのErythrocyte Binding-Likeタンパク質は赤血球侵入過程における不可逆的結合形成に重要である

著者名

外川裕人

学位授与大学

Nagasaki University (長崎大学) (大学ID:0073) (CAT機関ID:KI000877)

取得学位

博士(医学)

学位授与番号

甲医歯薬第1093号

学位授与年月日

2018-09-05

注記・抄録

Plasmodium malaria parasites multiply within erythrocytes and possess a repertoire of proteins whose function is to recognize and invade these vertebrate host cells. One such protein involved in erythrocyte invasion is the micronemal protein, Erythrocyte Binding-Like (EBL), which has been studied as a potential target of vaccine development in Plasmodium vivax (PvDBP) and Plasmodium falciparum (EBA-175). In the rodent malaria parasite model Plasmodium yoelii, specific substitutions in the EBL regions responsible for intracellular trafficking (17XL parasite line) or receptor recognition (17X1.1pp. parasite line), paradoxically increase invasion ability and virulence rather than abolish EBL function. Attempts to disrupt the ebl gene locus in the 17XL and 17XNL lines were unsuccessful, suggesting EBL essentiality. To understand the mechanisms behind these potentially conflicting outcomes, we generated 17XL-based transfectants in which ebl expression is suppressed with anhydrotetracycline (ATc) and investigated merozoite behavior during erythrocyte invasion. In the absence of ATc, EBL was secreted to the merozoite surface, whereas following ATc administration parasitemia was negligible in vivo. Merozoites lacking EBL were unable to invade erythrocytes in vitro, indicating that EBL has a critical role for erythrocyte invasion. Quantitative time-lapse imaging revealed that with ATc administration a significant number of merozoites were detached from the erythrocyte after the erythrocyte deformation event and no echinocytosis was observed, indicating that EBL is required for merozoites to establish an irreversible connection with erythrocytes during invasion.

開始ページ : 706

終了ページ : 714

元資料の権利情報 : © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/BY-NC-ND/4.0/).

キーワード

Invasion, Malaria, Plasmodium yoelii, Erythrocyte, EBL, Time-lapse imaging

各種コード

NII論文ID(NAID)

500001081057

NII著者ID(NRID)
  • 8000001205376
DOI (出版社)

10.1016/j.parint.2018.07.006

DOI

info:doi/10.1016/j.parint.2018.07.006

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

DOI

博士論文 / 長崎大学 / 医学

博士論文 / 長崎大学

博士論文 / 医学

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