Molecular Basis of Transport of Virulence Factors in the Pathogenic Protist

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390119
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: TOMOYOSH Nozaki National Institute of Infectious Diseases, 寄生動物部, 部長 (60198588)
• Co-Investigator(Kenkyū-buntansha): KUMIKO Tsukui 国立感染症研究所, 寄生動物部, 主任研究官 (00420092)
• Project Period (FY): 2008 – 2010
• 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

We identified and characterized a putative receptor/carrier for cysteine proteases, which is believed to play a pivotal role in pathogenesis of the enteric protozoan parasite Entamoeba histolytica. We also identified the members of cysteine protease genes that are stage-specifically expressed during differentiation.

Research Products

• [Journal Article] Cytotoxic effect of amide derivatives of trifluoromethionine to the enteric protozoan parasite Entamoeba histolytica. (2010)
  • Author(s): Sato. D., Kobayashi S., Yasui H., Shibata N., Toru T., Yamamoto M., Tokoro G., Ali V., Soga T., Takeuchi T., Suematsu M., Nozaki T.
  • Journal Title: Int.J.Antimicrob.Agents. 35 Pages: 56-61
• [Journal Article] Bacterial-type oxygen detoxification and iron-sulphur cluster assembly in amoebal relict mitochondria Cell. (2010)
  • Author(s): Maralikova B., Ali V., Nakada-Tsukui K., Nozaki T., van der Giezen M., Henze K., Tovar J.
  • Journal Title: Microbiol. 12 Pages: 331-342
• [Journal Article] Characterization of two isotypes of L-threonine dehydratase from Entamoeba histolytica. (2010)
  • Author(s): Husain A., Jeelani G., Sato D., Ali V,, Nozaki T.
  • Journal Title: Mol.Biochem.Parasitol. 170 Pages: 100-104
• [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 9 Pages: 926-933
• [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. 126(Review) Pages: 337-347
• [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. 285 Pages: 26889-26899
• [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. 57 Pages: 389-399
• [Journal Article] Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis upon L-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. 285 Pages: 39160-39170
• [Journal Article] Isoform-dependent feedback regulation of serine O-acetyltransferase isoenzymes involved in L-cysteine biosynthesis of Entamoeba histolytica. (2009)
  • Author(s): Hussain S., Ali V., Jeelani G., Nozaki, T.
  • Journal Title: Mol.Biochem.Parasitol. 163 Pages: 39-47
• [Journal Article] Phosphatidylinositol-phosphates mediate cytoskeletal reorganization during phagocytosis via a unique modular protein consisting of RhoGEF/DH and FYVE domains in the parasitic protozoon Entamoeba histolytica. (2009)
  • Author(s): Nakada-Tsukui K., Okada H., Mitra B.N., Nozaki, T.
  • Journal Title: Cell.Microbiol. 11 Pages: 1471-1491
• [Journal Article] Methionine gamma-lyase : the unique reaction mechanism, physiological roles, and therapeutic applications against infectious diseases and cancers. (2009)
  • Author(s): Sato D., Nozaki T.
  • Journal Title: IUBMB Life 61(Review) Pages: 1019-1028
• [Journal Article] Mitosomes in Entamoeba histolytica contain a sulfate activation pathway. (2009)
  • Author(s): Mi-ichi F., Yousuf M.A., Nakada-Tsukui K., Nozaki T.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 106 Pages: 21731-21736
• [Journal Article] An Entamoeba cysteine peptidase specifically expressed during encystation. (2008)
  • Author(s): Ebert F., Bachmann A., Nakada-Tsukui K., Hennings I., Drescher B., Nozaki T., Tannich E., Bruchhaus I.
  • Journal Title: Parasitol.Int. 57 Pages: 521-524
• [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 45^<th> US-Japan Cooperative Medical Science 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 45^<th> 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 45^<th> 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 45^<th> 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 45^<th> 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 45^<th> 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 45^<th> 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 45^<th> 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(WS進化からみたタンパク質社会)
  • 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 Symposiumfor the 26^<th> 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, Massachusetts, 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): 野崎智義
  • Organizer: The 18^<th> 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
• [Presentation] Mitosomes in the enteric protozoan parasite Entamoeba histolytica contain a sulfate activation pathway. Adaptive and Innate Immune Response to Neglected Tropical Diseases. (2010)
  • Author(s): 野崎智義
  • Organizer: US-Japan Cooperative Medical Science Program.
  • Place of Presentation: San Diego
  • Year and Date: 20100110-20100111
• [Presentation] 真核生物におけるミトコンドリアの多様性:腸管寄生原虫赤痢アメーバの新規オルガネラの解析 (2009)
  • Author(s): 野崎智義
  • Organizer: 第9回日本ミトコンドリア学会年会
  • Place of Presentation: 東京
  • Year and Date: 20091217-20091219
• [Presentation] ミトコンドリア関連オルガネラの新規機能ー赤痢アメーバ原虫"sulfosome"に存在する硫酸活性化経路ー (2009)
  • Author(s): 見市文香、野崎智義
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Presentation] 赤痢アメーバ等における小胞輸送の多様性と進化 (2009)
  • Author(s): 津久井久美子、Aleyla Escueta、中野由美子、野崎智義
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Presentation] イノシトールリン脂質シグナルを介した赤痢アメーバ貪食制御機構 (2009)
  • Author(s): 津久井久美子、野崎智義
  • Organizer: 第8回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 大阪
  • Year and Date: 20091009-20091010
• [Presentation] Rab small GTPases and phosphatidylinositides regulate phagocytosis and membrane trafficking of virulence factors : their roles in the pathogenesis of amebiasis. (2009)
  • Author(s): 野崎智義
  • Organizer: XVIIIth Congress of Parasitology
  • Place of Presentation: Aguascalientes, Mexico
  • Year and Date: 20090921-20090926
• [Presentation] Functional analysis of a putative cysteine protease receptor from Entamoeba histolytica. (2009)
  • Author(s): Furukawa A., Nakada-Tsukui K., Yamada Y., Nozaki T.
  • Organizer: The XXth Molecular Parasitology Meeting
  • Place of Presentation: Woods Hole
  • Year and Date: 20090913-20090917
• [Presentation] Biochemical and physiological function of a novel reductase from the microaerophilic protozoan parasite Entamoeba histolytica. (2009)
  • Author(s): Jeelani G., Husain A., Sato D., Suematsu M., Ali V., Nozaki T.
  • Organizer: The 9th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji
  • Year and Date: 20090908-20090911
• [Presentation] Metabolomic and transcriptomic analysis of sulfur-containing amino acid metabolism in enteric protozoan parasite Entamoeba histolytica. (2009)
  • Author(s): Husain A., Jeelani G., Sato D., Mi-ichi F., Soga T., Suematsu M., Ali V., Nozaki T.
  • Organizer: The 9th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji
  • Year and Date: 20090908-20090911
• [Presentation] ミトコンドリア関連オルガネラの新規機能ー赤痢アメーバ原虫マイトソームに存在する活性硫酸合成経路ー (2009)
  • Author(s): 見市文香、モハンマドアブユースフ、津久井久美子、川合覚、野崎智義
  • Organizer: 第78回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 20090327-20090328
• [Presentation] 赤痢アメーバシステインプロテアーゼ結合タンパク質の機能解析 (2009)
  • Author(s): 古川敦、津久井久美子、山田陽子、野崎智義
  • Organizer: 第78回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 20090327-20090328
• [Presentation] Entamoeba属シスト化におけるオートファジーの関与 (2009)
  • Author(s): 津久井久美子、Picazarri Delgado Karina、古川敦、野崎智義
  • Organizer: 第78回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 20090327-20090328
• [Presentation] Role of sulfur-containing amino acid metabolism : characterization of two isotypes of methionine gamma-lyase in Entamoeba histolytica. XVI Seminario Sobre Amibiasis and EMBO Workshop. (2009)
  • Author(s): Nozaki T., Furukawa A., Jeelani G., Sato D., Karaki T., Harada S.
  • Organizer: Amoebiasis : Molecular Approaches in an Important but Neglected Disease.
  • Place of Presentation: Guanajuato, Mexico
  • Year and Date: 20090224-20090228
• [Presentation] Identification of a putative receptor of the major virulence factor cysteine protease in the enteric protist Entamoeba histolytica. XVI Seminario Sobre Amibiasis and EMBO Workshop. (2009)
  • Author(s): Nakada-Tsukui K., Furukawa A., Yamada Y., Nozaki T.
  • Organizer: Amoebiasis : Molecular Approaches in an Important but Neglected Disease.
  • Place of Presentation: Guanajuato, Mexico
  • Year and Date: 20090224-20090228
• [Presentation] Autophagy in E.histolytica. XVI Seminario Sobre Amibiasis and EMBO Workshop. (2009)
  • Author(s): Picazarri K., Furukawa A., Sato D., Nakada-Tsukui K., Nozaki T.
  • Organizer: Amoebiasis : Molecular Approaches in an Important but Neglected Disease.
  • Place of Presentation: Guanajuato, Mexico.
  • Year and Date: 20090224-20090228
• [Presentation] The mitochondria-related organelle in the anaerobic protist Entamoeba histolytica. (2008)
  • Author(s): Mi-ichi F., Abu Y.M., Nakada-Tsukui K., Kawai S., Nozaki T.
  • Organizer: International Symposium : Bacteria made ornangelles made eukaryotic cells.
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20081129-20081130
• [Presentation] The mitochondria-related organelle in the anaerobic parasitic protozoon Entamoeba histolytica. (2008)
  • Author(s): Mi-ichi F., Abu Y.M., 津久井久美子, Kawai S., Nozaki T.
  • Organizer: International Symposium on Protistology : Evolution and Diversity.
  • Place of Presentation: Tsukuba, Japan
  • Year and Date: 20081108-20081109
• [Presentation] Regulation of cysteine protease secretion and phagocytosis in Entamoeba histolytica. (2008)
  • Author(s): 野崎智義
  • Organizer: XVIIth International Congress for Tropical Medicine and Malaria (Invited talk in the symposium)
  • Place of Presentation: Jeju, Korea
  • Year and Date: 20080929-20081003
• [Presentation] Metabolomic and transcriptomic analysis of sulfur-containing amino acid metabolism in the enteric protozoan parasite Entamoeba histolytica. (2008)
  • Author(s): Husein A., Jeelani G., Bilal A.S.,Sato D., Mi-ichi F., Hishiki T., Gilchrist C.A., Suematsu M., Petri W.A., Jr., Nozaki T.
  • Organizer: The 8th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji
  • Year and Date: 20080907-20080911
• [Presentation] Characterization of methionine gamma-lyases from enteric protozoan parasite, Entamoeba histolytica, as a potential drug target against amoebiasis (2008)
  • Author(s): Sato D., Yamagata W., Karaki T., Shimizu A., Harada S., Nozaki T.
  • Organizer: The 8th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji
  • Year and Date: 20080907-20080911
• [Presentation] 原虫におけるメンブレントラフィックの多様性 (2008)
  • Author(s): 中野由美子、中野賢太郎、野崎智義
  • Organizer: 第10回日本進化学会大会
  • Place of Presentation: 東京
  • Year and Date: 20080822-20080824
• [Presentation] 赤痢アメーバ原虫のミトコンドリア残存オルガネラmitosomeの特殊性～その機能と役割～ (2008)
  • Author(s): 見市文香、野崎智義
  • Organizer: 第10回日本進化学会大会
  • Place of Presentation: 東京
  • Year and Date: 20080822-20080824
• [Presentation] A FYVE domain and RhoGEF domain-containing protein involved in phagocytosis of a mammalian cell by Entamoeba histolytica. (2008)
  • Author(s): 津久井久美子, 野崎智義
  • Organizer: 第60回細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 20080629-20080701
• [Presentation] Kinetic characterizationof methionine gamma-lyase from Entamoeba histolytica against physiological substrates and trifluoromethionine. (2008)
  • Author(s): Sato D., Yamagata W., Karaki T., Harada S., Nozaki T.
  • Organizer: The 4th International Conference on Anaerobic Protists : The Systems Biology of Anaerobic Protozoa.
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20080512-20080516
• [Presentation] A FYVE and RhoGEF domain-containing protein involved in phagocytosis of a mammalian cell by Entamoeba histolytica. (2008)
  • Author(s): 津久井久美子
  • Organizer: The 4th International Conference on Anaerobic Protists : The Systems Biology of Anaerobic Protozoa.
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20080512-20080516
• [Presentation] Unique role of the autophagic pathway in the protozoan parasite Entamoeba histolytica.
  • Author(s): Nakada-Tsukui K., Picazzari K., Tsuboi K., Nozai T.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 00001209-00001212
• [Book] Genomes of Food- and Water-borne Pathogens(Editted by Pina Fratamico, Sophia Kathariou, and Yanhong Liu)(Genomic and post-genomic approaches to understand the pathogenesis of the enteric protozoan parasite Entamoeba histolytica. ISBN:978-1-55581-457-1) (2011)
  • Author(s): Kumiko Nakada-Tsukui, Tomoyoshi Nozaki
  • Publisher: ASM Press, Washington, D.C.
• [Book] Anaerobic Parasitic Protozoa : Genomics and Molecular Biology(Editted by C.Graham Clark, Patricia J.Johnson and Rodney D.Adam)(Dissecting the Actin Cytoskeleton of Entamoeba histolytica from a Genomic Perspective. ISBN:978-1-904455-61-5) (2010)
  • Author(s): Chung Chau Hon, Kumiko Nakada-Tsukui, Tomoyoshi Nozaki, Nancy Guilen
  • Publisher: Caister Academic Press
• [Remarks] ホームページ等
  • URL: http://www.nih.go.jp/niid/para/parasite.html