病原性原虫の病原因子輸送の分子基盤に関する研究

2010 Fiscal Year Annual Research Report

• Project/Area Number: 20390119
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: 野崎 智義 国立感染症研究所, 寄生動物部, 部長 (60198588)
• Keywords: 小胞輸送 / 病原機構 / 感染症 / 寄生虫 / システインプロテアーゼ

Research Abstract

赤痢アメーバ症はマラリアに次いで死亡者数の多い原虫性感染症であり、発展途上国だけでなく、わが国でも知的障害者などに濃厚な感染を起こしている。本研究では赤痢アメーバの生存と寄生・病原に必須なシステインプロテアーゼ(CP)の輸送ならびに活性調節機構を、生化学的・細胞化学的・逆遺伝学的手法を駆使し解明するとともに、トランスクリプトーム・プロテオームなどの"-omics"手法を応用した統合的アプローチにより多様なCP遺伝子群の機能的特異性を解明することを目的とする赤痢アメーバはゲノムに>40ものCP遺伝子をもち、腸管上皮や肝細胞などの傷害、免疫細胞の貪食・分解による免疫回避、細菌などの貪食・分解による栄養摂取などに関与するとされているが、それぞれのCPの機能的相違・特異性ほとんど理解されていない。また、CPの細胞内での輸送機構、活性の調節機構などの分子基盤は十分に理解されていない。本年度は、CP輸送体(CPBF1)の機能解析を行い、赤痢アメーバの細胞内におけるリソソームやファゴソームへのCPの輸送に、CPBF1が必須であることが示された。更に、CPの内因性阻害タンパク質ICPの立体構造を解明するために、結晶化の至適条件を確立した。また、ヘビアメーバの嚢子化過程で発現の変動するCPに関して、詳細なプロファイリングを行い、ステージ特異的CPの注釈付けを完了した。

Research Products

• [Journal Article] Localization and targeting of unusual pyridine nucleotide transhydrogenase in Entamoeba histolytica. (2010)
  • Author(s): Yousuf, M.A., Mi-ichi, F., Nakada-Tsukui, K., Nozaki, T.
  • Journal Title: Eukaryot.Cell Volume: 9 Pages: 926-933
  • Peer Reviewed
• [Journal Article] Conservation and function of Rab small GTPases in Entamoeba : annotation of E.invadens Rab and its use for the understanding of Entamoeba biology. (2010)
  • Author(s): Nakada-Tsukui, K., Saito-Nakano, Y., Husain, A., Nozaki, T.
  • Journal Title: Exp.Parasitol Volume: 126 Pages: 337-347
  • Peer Reviewed
• [Journal Article] Two Atypical L-cysteine-regulated NADPH-dependent oxidoreductases involved in redox maintenance, L-cystine reduction, and metronidazole activation in the enteric protozoon Entamoeba histolytica (2010)
  • Author(s): Jeelani, G., Husain, A., Sato, D., Ali, V., Suematsue, M., Soga, T., Nozaki, T.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 26889-26899
  • Peer Reviewed
• [Journal Article] Marked amplification and diversification of Rab GTPases in ciliates Tetrahymena thermophila and Paramecium tetraurelia (2010)
  • Author(s): Saito-Nakano, Y., Nakahara, T., Nakano, K., Nozaki, T., Numata, O.
  • Journal Title: J.Eukaryot.Microbiol. Volume: 57 Pages: 389-399
  • Peer Reviewed
• [Journal Article] Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis uponL-cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica. (2010)
  • Author(s): Husain, A., Sato, D., Jeelani, G., Suematsu, M., Soga, T., Nozaki, T.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 39160-39170
  • Peer Reviewed
• [Presentation] Diversity of vesicular trafficking in phagocytic protozoa and significance of traffic in Entamoeba histolytica. (2011)
  • Author(s): Saito-Nakano, Y., Nakano, K., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative MedicalScience Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Mechanism of trifluoromethionine resistance in Entamoeba histolytica. (2011)
  • Author(s): Penuliar, G.M., Furukawa, A., Sato, D., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Entamoeba invadens : transcriptome analysis during encystation. (2011)
  • Author(s): Escueta-de Cadiz, A., Nakada-Tsukui, K., Caler, E., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Metabolomic analysis during differentiation of enteric protozoan parasite Entamoeba histolytica into the infectious cyst stage. (2011)
  • Author(s): Jeelani, G., Sato, D., Husein, A., Suematsu, M., Soga, T., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Traffiking mechanisms of phagosomal proteins in Entamoeba histolytica. (2011)
  • Author(s): Furukawa, A., Nakada-Tsukui, K., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Gene silencing of mitosomal proteins causes growth inhibition and suggests essentiality of mitosomes in Entamoeba histolytica. (2011)
  • Author(s): Mi-ichi, F, Yousuf, A., Makiuchi, T., Nakada-Tsukui, K., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Metabolomic analysis of sulfur containing amino acid metabolism in E.histolytica. (2011)
  • Author(s): Husain, A., Sato, D., Jeelani, G., Mi-ichi, F., Ali, V., Suematsu, M., Soga, T., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Analysis of the protein import machinery in the Entamoeba mitochondrial remnant. (2011)
  • Author(s): Makiuchi, T., Mi-ichi, F., Nakada-Tsukui, K., Nozaki, T.
  • Organizer: The 45th US-Japan Cooperative Medical Science Program
  • Place of Presentation: Tokyo
  • Year and Date: 20110110-20110112
• [Presentation] Functional diversity of mitochondrion-related organelles in eukaryotes. (2010)
  • Author(s): Nozaki, T., Mi-ichi, F., Makiuchi, T., Yousuf, M.A., Nakada-Tsukui, K.
  • Organizer: 第33回日本分子生物学会年会、第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] Analysis of the protein import machinery in the Entamoeba mitochondrial remnant. (2010)
  • Author(s): Makiuchi, T., Mi-ichi, F., Nakada-Tsukui, K., Nozaki, T.
  • Organizer: Biology of Symbiosis : Memorial Symposium for the 26th International Prize for Biology-Celebrating Dr.Nancy A.Moran.
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 20101207-20101208
• [Presentation] Diversity and significance of vesicular trafficking in Entamoeba histolytica. (2010)
  • Author(s): Saito-Nakano Y., Okada. M., Penuliar G.M., Hanadate Y., Gilchrist C.A., Crasta O., Petri Jr., W.A., Fei Z., Trapaidze Ni., Nozaki T.
  • Organizer: Amebiasis Workshop 2010, "Molecular Approaches and Clinical Aspects"
  • Place of Presentation: Montreal
  • Year and Date: 20100922-20100924
• [Presentation] Metabolomic analysis of Entamoeba : discovery of unique pathways and potential targets for chemotherapy. (2010)
  • Author(s): Nozaki T., Husain A., Jeelni G, Sato D., Suematsu M., Soga T.
  • Organizer: Amebiasis Workshop 2010, "Molecular Approaches and Clinical Aspects"
  • Place of Presentation: Montreal
  • Year and Date: 20100922-20100924
• [Presentation] Mechanism of trifluoromethionine resistance in Entamoeba histolytica. (2010)
  • Author(s): Penuliar G., Nozaki T.
  • Organizer: Amebiasis Workshop 2010, "Molecular Approaches and Clinical Aspects"
  • Place of Presentation: Montreal
  • Year and Date: 20100922-20100924
• [Presentation] Entamoeba invadens : Transcriptome analysis during encystation. (2010)
  • Author(s): Escueta-de Cadiz, A., Nakada-Tsukui, K., Caler, E., Nozaki, T.
  • Organizer: 21st Molecular Parasitology Meeting
  • Place of Presentation: WoodsHole, USA
  • Year and Date: 20100912-20100916
• [Presentation] Mitosomes from the enteric protozoan parasite Entamoeba histolytica possess unique functions and minimal import machinery. (2010)
  • Author(s): 野崎智義
  • Organizer: The XIIth International Congress of Parasitology.
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 20100815-20100820
• [Presentation] Unprecedented role of the mitosome in Entamoba histolytica. (2010)
  • Author(s): Nozaki, T.
  • Organizer: The 18th Meeting of the International Society for Evolutionary Protistology
  • Place of Presentation: Kanazawa, Japan
  • Year and Date: 20100702-20100707
• [Presentation] Metabolic analysis of the human enteric parasite Entamoeba histolytica : Discovery of unique pathways and potential targets for chemotherapeutics. (2010)
  • Author(s): Sato D., Husain A., Jeelani G., Suematsu M., Soga T., Nozaki T.
  • Organizer: Metabolomics 2010
  • Place of Presentation: Amsterdam, The Netherlands
  • Year and Date: 20100627-20100701
• [Presentation] Metabolomics of parasite differentiation : metabolomic profiling of the human enteric protozoan parasite Entamoeba histolyitca revealed activation of unpredicted pathways during differentiation of the proliferative into dormant stage. (2010)
  • Author(s): Jeelani G., Sato D., Jusain A., Suematsu M., Soga T., Nozaki T.
  • Organizer: Metabolomics 2010
  • Place of Presentation: Amsterdam, The Netherlands
  • Year and Date: 20100627-20100701
• [Presentation] 赤痢アメーバにおける病原性因子輸送機構の分子論的解明:新規システインプロテアーゼレセプターの同定と機能解析 (2010)
  • Author(s): 古川敦、津久井久美子、山田陽子、坪井久美子、野崎智義
  • Organizer: 第79回日本寄生虫学会大会
  • Place of Presentation: 旭川
  • Year and Date: 20100520-20100521
• [Presentation] 赤痢アメーバ原虫"mitosome"に存在する硫酸活性化経路の生理機能の解明 (2010)
  • Author(s): 見市文香、牧内貴志、モハンマド・アブ・ユースフ、野崎智義
  • Organizer: 第79回日本寄生虫学会大会
  • Place of Presentation: 旭川
  • Year and Date: 20100520-20100521
• [Presentation] Entamoebaマイトソームにおけるタンパク質輸送機構の解析 (2010)
  • Author(s): 牧内貴志、見市文香、津久井久美子、野崎智義
  • Organizer: 第79回日本寄生虫学会大会
  • Place of Presentation: 旭川
  • Year and Date: 20100520-20100521
• [Book] Dissecting the Actin Cytoskeleton of Entamoeba histolytica from a Genomic Perspective.(Anaerobic Parasitic Protozoa : Genomics and Molecular Biology) (2010)
  • Author(s): Chung Chau Hon, Kumiko Nakada-Tsukui, Tomoyoshi Nozaki, Nancy Guillen.
  • Total Pages: 222
  • Publisher: Caister Academic Press
• [Book] Genomic and post-genomic approaches to understand the pathogenesis of the enteric protozoan parasite Entamoeba histolytica.(Genomes of Food- and Water-borne Pathogens) (2010)
  • Author(s): Kumiko Nakada-Tsukui, Tomoyoshi Nozaki.
  • Total Pages: 352
  • Publisher: ASM Press, Washington, D.C.
• [Remarks]
  • URL: http://www.nih.go.jp/niid/para/parasite.html