The molecular interactions between host and liver stage malaria parasites through the parasitophorous vacuole membrane.

• Project/Area Number: 25860311
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: National Institute of Infectious Diseases (2014); Jikei University School of Medicine (2013)
• Principal Investigator: ANNOURA Takeshi 国立感染症研究所, その他部局等, 研究員 (90407239)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: マラリア / 原虫 / 寄生胞膜 / 肝内型 / 肝内型原虫 / 分子間相互作用 / 原虫‐宿主相互作用

Outline of Final Research Achievements

Malaria is a major global health burden, and Plasmodium is the causative agents of malaria. In order to reveal the molecular interplay between Plasmodium and the host, we focus on plasmodium liver stage development especially parasitophorous vacuole membrane (PVM), which an interface membrane between parasite and host. Loss-of-function analyses have revealed that B9 is specifically expressed in Plasmodium liver stages and that is important to parasite development in both rodent and human Plasmodium. And also b9 is readily transcribed in sporozoites, B9 protein is present after hepatocyte invasion. Moreover we show that B9 is localized on the parasite plasma membrane where it plays an important role in establishment and maintenance of PVM inside the hepatocyte. Based on the structural analyses of B9 4-cysteine domain, we propose that the presence of the four positionally conserved cysteine residues, are diagnostic for this domain and B9 belong to the 6-Cys family-related proteins.

Research Products

• [Journal Article] Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance. (2015)
  • Author(s): Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RB, Aime E, Capuccini B, Mommaas-Kienhuis AM, O'Toole T, Prins F, Franke-Fayard BM, Ramesar J, Chevalley-Maurel S, Kroeze H, Koster AJ, Tanke HJ, Crisanti A, Langhorne J, Arese P, Van den Steen PE, Janse CJ, Khan SM.
  • Journal Title: J Exp Med. Volume: in press
  • Peer Reviewed
• [Journal Article] In vivo and in vitro characterization of a Plasmodium liver stage-specific promoter. (2015)
  • Author(s): De Niz M, Helm S, Horstmann S, Annoura T, Del Portillo HA, Khan SM, Heussler VT.
  • Journal Title: PLoS One. Volume: 10(4) Issue: 4 Pages: e0123473-e0123473
  • DOI: 10.1371/journal.pone.0123473
  • Peer Reviewed / Open Access
• [Journal Article] A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites. (2014)
  • Author(s): van Schaijk BC, Ploemen IH, Annoura T, Vos MW, Foquet L, van Gemert GJ, Chevalley-Maurel S, van de Vegte-Bolmer M, Sajid M, Franetich JF, Lorthiois A, Leroux-Roels G, Meuleman P, Hermsen CC, Mazier D, Hoffman SL, Janse CJ, Khan SM, Sauerwein RW.
  • Journal Title: Elife. Volume: 3.
  • DOI: 10.7554/elife.03582
  • Peer Reviewed / Open Access
• [Journal Article] The subcellular location of ovalbumin in Plasmodium berghei blood stages influences the magnitude of T-cell responses. (2014)
  • Author(s): Lin JW, Shaw TN, Annoura T, Fougère A, Bouchier P, Chevalley-Maurel S, Kroeze H, Franke-Fayard B, Janse CJ, Couper KN, Khan SM.
  • Journal Title: Infect Immun. Volume: 82(11) Issue: 11 Pages: 4654-65
  • DOI: 10.1128/iai.01940-14
  • Peer Reviewed
• [Journal Article] Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development. (2014)
  • Author(s): Annoura T, van Schaijk BC, Ploemen IH, Sajid M, Lin JW, Vos MW, Dinmohamed AG, Inaoka DK, Rijpma SR, van Gemert GJ, Chevalley-Maurel S, Kiełbasa SM, Scheltinga F, Franke-Fayard B, Klop O, Hermsen CC, Kita K, Gego A, Franetich JF, Mazier D, Hoffman SL, Janse CJ, Sauerwein RW, Khan SM.
  • Journal Title: FASEB J. Volume: 28(5) Issue: 5 Pages: 2158-70
  • DOI: 10.1096/fj.13-241570
  • Peer Reviewed
• [Journal Article] Plasmodium liver load following parenteral sporozoite administration in rodents. (2013)
  • Author(s): Ploemen IH, Chakravarty S, van Gemert GJ, Annoura T, Khan SM, Janse CJ, Hermsen CC, Hoffman SL, Sauerwein RW.
  • Journal Title: Vaccine. Volume: 31(34) Issue: 34 Pages: 3410-6
  • DOI: 10.1016/j.vaccine.2012.09.080
  • Peer Reviewed
• [Presentation] 肝内型マラリア原虫における分泌タンパク質：細胞内局在性の変化と肝内期を介することで起こる発現切り替え (2015)
  • Author(s): 案浦健, Jannik Fonager, Joanna A. Braks, Onny Klop, Chris J. Janse, Shahid M. Khan, Blandine Franke-Fayard,.
  • Organizer: 第８４回日本寄生虫学会大会
  • Place of Presentation: 杏林大学三鷹キャンパス
  • Year and Date: 2015-03-21
• [Presentation] 肝内型マラリア原虫と宿主の“鬩ぎ合い”分子メカニズムの解明 (2014)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 浅井史敏, Khan SM, Heussler VT, 嘉糠 洋陸
  • Organizer: 第２２回分子寄生虫学ワークショップ／第１２回分子寄生虫・マラリア研究フォーラム合同大会
  • Place of Presentation: 帯広畜産大学・原虫病研究センター PKホール
  • Year and Date: 2014-08-31
• [Presentation] 肝内型マラリア原虫と宿主の“鬩ぎ合い”分子メカニズム (2014)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 浅井史敏, Khan SM, Heussler VT, 嘉糠 洋陸
  • Organizer: 第８回細菌学若手コロッセウム
  • Place of Presentation: ホテルニセコ いこいの村
  • Year and Date: 2014-08-06
  • Invited
• [Presentation] 偽オルガネラとしての肝内型マラリア原虫の宿主内“居座り”分子基盤 (2014)
  • Author(s): 案浦 健, 荒木 球沙, Franke-Fayard BM, Janse CJ, 浅井史敏, Khan SM, Heussler VT, 嘉糠 洋陸
  • Organizer: 第３回マトリョーシカ型生物学研究会 神戸2014
  • Place of Presentation: 神戸大学百年記念館 (神大会館)
  • Year and Date: 2014-07-11
• [Presentation] New members of the Plasmodium 6-Cys family have distinct and critical roles (2014)
  • Author(s): Takeshi Annoura, Ben C.L. van Schaijk, Ivo H.J. Ploemen, Mohammed Sajid, Daniel K. Inaoka, Geert-Jan van Gemert, Severine Chevalley-Maurel, Blandine M.D. Franke-Fayard, Audrey Gego, Kiyoshi Kita, Dominique Mazier, Stephen L. Hoffman, Chris J. Janse, Robert W. Sauerwein, Hirotaka Kanuka and Shahid M. Khan
  • Organizer: 第３回 感染症若手フォーラム
  • Place of Presentation: やすらぎ伊王島
• [Presentation] 肝内型マラリア原虫の寄生胞膜形成；新たな特異分子“B9”の役割 (2014)
  • Author(s): 案浦健, van Schaijk BC, Ploemen IH, Sajid M, Franke-Fayard BM, 稲岡ダニエル健, 北潔, Mazier D, Hoffman SL, Sauerwein RW, Heussler VT, Janse CJ, Khan SM, 嘉糠洋陸
  • Organizer: 第８３回 日本寄生虫学会大会
  • Place of Presentation: 愛媛大学
• [Presentation] 肝内型マラリア原虫特異的分子“B9”と寄生胞膜に果たす役割 (2013)
  • Author(s): 案浦健, van Schaijk BC, Ploemen IH, Sajid M, Franke-Fayard BM, 稲岡ダニエル健, 北潔, Mazier D, Hoffman SL, Sauerwein RW, Heussler VT, Janse CJ, Khan SM, 嘉糠洋陸
  • Organizer: 第21回分子寄生虫学ワークショップ
  • Place of Presentation: 神戸セミナーハウス
• [Presentation] 肝内型マラリア原虫；寄生と共生の境界 (2013)
  • Author(s): 案浦健, van Schaijk BC, Ploemen IH, Sajid M, Franke-Fayard BM, 稲岡ダニエル健, 北潔, Mazier D, Hoffman SL, Sauerwein RW, Heussler VT, Janse CJ, Khan SM, 嘉糠洋
  • Organizer: 第２回 日本細胞共生学会 若手の会
  • Place of Presentation: 京都大学
• [Presentation] 肝内型マラリア原虫特異的分子“B9”と寄生胞膜に果たす役割 (2013)
  • Author(s): 案浦健, van Schaijk BC, Ploemen IH, Sajid M, Franke-Fayard BM, 稲岡ダニエル健, 北潔, Mazier D, Hoffman SL, Sauerwein RW, Heussler VT, Janse CJ, Khan SM, 嘉糠洋
  • Organizer: 第１１回 分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 長崎大学
• [Presentation] 肝内型マラリア原虫-宿主間“せめぎ合い”メカニズムの解明 (2013)
  • Author(s): 案浦健, van Schaijk BC, Ploemen IH, Sajid M, Franke-Fayard BM, 稲岡ダニエル健, 北潔, Mazier D, Hoffman SL, Sauerwein RW, Heussler VT, Janse CJ, Khan SM, 嘉糠洋陸
  • Organizer: 第３６回 日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
• [Book] 細胞工学 連載企画 「細胞進化の証人たち」 よそさまのお宿に棲むという細胞進化‐細胞内寄生成立モデル‐：トリパノソーマほか (2014)
  • Author(s): 案浦健
  • Total Pages: 2
  • Publisher: 学研メディカル秀潤社
• [Book] 動物用ワクチン-バイオ医薬品研究会ニュースレター「マラリアワクチン開発の現状と展望」 (2014)
  • Author(s): 案浦健
  • Total Pages: 5
  • Publisher: 一般財団法人 生物科学安全研究所