Host and tissue specificity of Trypanosoma cruzi in the wild reservoirs

• Project/Area Number: 24390102
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Juntendo University
• Principal Investigator: Nara Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (40276473)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Muneaki 順天堂大学, 医学部, 准教授 (30407308) ; TSUBOUCHI Akiko 順天堂大学, 医学部, 助教 (10398662) ; MORALES Jorge 順天堂大学, 医学部, 助教 (20596126)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: シャーガス病 / Trypanosoma cruzi / 臓器特異性 / 自然宿主 / 休眠 / 寄生適応進化 / 適応戦略 / 慢性化 / 休眠体 / 生適応進化 / 感染モデル創出

Outline of Final Research Achievements

Chagas disease is caused by infection of the parasitic protist, Trypanosoma cruzi. T. cruzi can persist for decades and 10-30% of the patients enter into the chronic stage, which is characterized by heart failure and/or megadisease. The long-term persistence of pathogens like Toxoplasma is generally associated with a cyst or “a dormant form”. Iralu has reported induction of a cyst-like form of T. cruzi by treatment with urease (Nature 204:486 1964), whereas no further report has described T. cruzi cysts. In the present study, we reanalyzed cyst formation in T. cruzi and found that a lectin, concanavalin A (ConA), can successfully induce the cyst formation. T. cruzi epimastigotes treated with ConA developed a large vacuole inside the cell and the organelles began to divide in the cytoplasm. Our findings provide important insights into the mechanism of transmission and persistence of the parasite.

Research Products

• [Journal Article] Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids. (2016)
  • Author(s): Morales J, Hashimoto M, Williams TA, Hirawake-Mogi H, Makiuchi T, Tsubouchi A, Kaga N, Taka H, Fujimura T, Koike M, Mita T, Bringaud F, Concepcion JL, Hashimoto T, Embley TM, Nara T.
  • Journal Title: Proc R Soc B Volume: 283 Issue: 1830 Pages: 20160520-20160520
  • DOI: 10.1098/rspb.2016.0520
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Morpholino antisense oligo inhibits trans-splicing of pre-inositol 1,4,5-trisphosphate receptor mRNA of Trypanosoma cruzi and suppresses parasite growth and infectivity. (2016)
  • Author(s): Hashimoto M, Nara T, Mita T, Mikoshiba K.
  • Journal Title: Parasitol Int. Volume: 65 Issue: 3 Pages: 175-179
  • DOI: 10.1016/j.parint.2015.12.001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells. (2016)
  • Author(s): Kobayashi I, Takahashi F, Nurwidya F, Nara T, Hashimoto M, Murakami A,
  • Journal Title: Biochem Biophys Res Commun Volume: in press Issue: 1 Pages: 125-132
  • DOI: 10.1016/j.bbrc.2016.03.064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Current situation of Chagas disease in non-endemic countries. (2015)
  • Author(s): Nara T.
  • Journal Title: Juntendo Med J Volume: 61 Pages: 389-395
  • NAID: 130005111511
  • Peer Reviewed
• [Journal Article] A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi. (2015)
  • Author(s): Hashimoto M, Nara T, Enomoto M, Kurebayashi N, Yoshida M, Sakurai T, Mita T, Mikoshiba K.
  • Journal Title: Biochem Biophys Res Commun Volume: 466 Issue: 3 Pages: 475-480
  • DOI: 10.1016/j.bbrc.2015.09.053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Novel Method for Inducing Amastigote-To-Trypomastigote Transformation In Vitro in Trypanosoma cruzi Reveals the Importance of Inositol 1,4,5-Trisphosphate Receptor. (2015)
  • Author(s): Hashimoto M, Morales J, Uemura H, Mikoshiba K, Nara T.
  • Journal Title: PLoS One. Volume: 10 Issue: 8 Pages: e0135726-e0135726
  • DOI: 10.1371/journal.pone.0135726
  • NAID: 120006986870
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] シャーガス病：感染症最前線とグローバル・ヘルス (2015)
  • Author(s): 奈良武司． 253: 119-123, 2015
  • Journal Title: 医学のあゆみ Volume: 253 Pages: 119-123
• [Journal Article] Current situation of Chagas disease in non-endemic countries (2015)
  • Author(s): Nara T.
  • Journal Title: Juntendo Med J Volume: in press
  • NAID: 130005111511
• [Journal Article] トリパノソーマ症：骨格筋症候群（第2版）上－その他の神経筋疾患を含めて－ (2015)
  • Author(s): 奈良武司
  • Journal Title: 日本臨牀 Volume: in press
• [Journal Article] Treatment with insulin-like growth factor 1 receptor inhibitor reverses hypoxia-induced epithelial-mesenchymal transition in non-small cell lung cancer (2014)
  • Author(s): Nurwidya F, Takahashi F, Kobayashi I, Murakami A, Kato M, Minakata K, Nara T, Hashimoto M, Yagishita S, Baskoro H, Hidayat M, Shimada N, Takahashi K.
  • Journal Title: Biochem Biophys Res Commun Volume: 455 Issue: 3-4 Pages: 332-338
  • DOI: 10.1016/j.bbrc.2014.11.014
  • Peer Reviewed
• [Journal Article] Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase (2014)
  • Author(s): Emmanuel Oluwadare Balogun, Daniel Ken Inaoka, Tomoo Shiba, Yasutoshi Kido, Chiaki Tsuge, Takeshi Nara, Takashi Aoki, Teruki Honma, Akiko Tanaka, Masayuki Inoue, Shigeru Matsuoka, Paul A.M. Michels, Kiyoshi Kita, Shigeharu Harada
  • Journal Title: Molecular Microbiology Volume: 94 Issue: 6 Pages: 1315-1329
  • DOI: 10.1111/mmi.12831
  • Peer Reviewed
• [Journal Article] Chagas disease: Clear and present danger (2014)
  • Author(s): Nara T.
  • Journal Title: Juntendo Med J Volume: 60 Pages: 362-365
• [Journal Article] Antisense oligonucleotides targeting parasite inositol 1,4,5-trisphosphate receptor inhibits mammalian host cell invasion by Trypanosoma cruzi (2014)
  • Author(s): Hashimoto M, Nara T, Hirawake H, Morales J, Enomoto M, Mikoshiba K.
  • Journal Title: Sci Rep Volume: 14(4231) Issue: 1 Pages: 4231-4231
  • DOI: 10.1038/srep04231
  • Peer Reviewed
• [Journal Article] Structure of the trypanosome cyanide-insensitive alternative oxidase (2013)
  • Author(s): Tomoo Shiba, Yasutoshi Kido, Kimitoshi Sakamoto, Daniel Ken Inaoka, Chiaki Tsuge, Ryoko Tatsumi,Gen Takahashi, Emmanuel Oluwadare Balogun, Takeshi Nara, Takashi Aoki, Teruki Honma, Akiko Tanaka, Masayuki Inoue, Shigeru Matsuoka, Hiroyuki Saimoto, Anthony L. Moore, Shigeharu Harada, Kiyoshi Kita
  • Journal Title: Proc. Nat1. Acad. Sci. USA Volume: 110 (12) Issue: 12 Pages: 4580-4585
  • DOI: 10.1073/pnas.1218386110
  • Peer Reviewed
• [Journal Article] Biochemical characterization of highly active Trypanosoma brucei gambiense glycerol kinase, a promising drug target (2013)
  • Author(s): Balogun EO, Inaoka DK, Shiba T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Harada S, Kita K
  • Journal Title: J Biochem Volume: 154(1) Issue: 1 Pages: 77-84
  • DOI: 10.1093/jb/mvt037
  • Peer Reviewed
• [Journal Article] Assessment of Cross-reactive Host-pathogen Antibodies in Patients With Different Stages of Chronic Chagas Disease (2013)
  • Author(s): Vicco MH, Ferini F, Rodeles L, Cardona P, Bontempi I, Lioi S, Beloscar J, Nara T, Marcipar I, Bottasso OA
  • Journal Title: Rev Esp Cardiol Volume: 66(10) Issue: 10 Pages: 791-796
  • DOI: 10.1016/j.recesp.2013.05.028
  • Peer Reviewed
• [Journal Article] Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor (2013)
  • Author(s): Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, Nara T, Kato M, Tajima K, Shimada N, Iwakami S, Moriyama M, Moriyama H, Koizumi F, Takahashi K
  • Journal Title: PLoS One Volume: 9(1) Issue: 1 Pages: e86459-e86459
  • DOI: 10.1371/journal.pone.0086459
  • Peer Reviewed
• [Journal Article] Inositol 1,4,5-Trisphosphate receptor regulates replication, differentiation, infectivity, and virulence of the parasitic protist Trypanosoma cruzi (2013)
  • Author(s): Hashimoto M
  • Journal Title: Mol Microbiology Volume: 87(6) Issue: 6 Pages: 1133-50
  • DOI: 10.1111/mmi.12155
  • Peer Reviewed
• [Journal Article] SUMOylation of paraflagellar rod protein, PFR1, and its stage-specific localization in Trypanosoma cruzi (2012)
  • Author(s): Annoura T, et al. (他4名)
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e37183-e37183
  • DOI: 10.1371/journal.pone.0037183
  • Peer Reviewed
• [Journal Article] Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors (2012)
  • Author(s): Minakata K, et al. (他12名)
  • Journal Title: Cancer Sci Volume: 103 Issue: 11 Pages: 1946-1954
  • DOI: 10.1111/j.1349-7006.2012.02408.x
  • Peer Reviewed
• [Journal Article] Prevalence of intestinal parasitic infections among primary schoolchildren in areas devoid of sanitation in northwestern Kingdom of Swaziland, Southern Africa (2012)
  • Author(s): Fan CK, et al. (他15名)
  • Journal Title: Pathog Glob Health 106(1): 60-62 Volume: 106 Issue: 1 Pages: 60-62
  • DOI: 10.1179/2047773211y.0000000017
  • Peer Reviewed
• [Journal Article] Toxoplasma gondii infection: relationship between seroprevalence and risk factors among primary schoolchildren in the capital areas of Democratic Republic of Sao Tome and Principe, West Africa (2012)
  • Author(s): Fan CK, et al. (他11名)
  • Journal Title: Parasit Vectors Volume: 5 Issue: 1 Pages: 141-141
  • DOI: 10.1186/1756-3305-5-141
  • Peer Reviewed
• [Journal Article] Enterobius vermicularis infection is well controlled among preschool children in nurseries of Taipei City, Taiwan (2012)
  • Author(s): Chu TB, et al. (他6名)
  • Journal Title: Rev Soc Bras Med Trop Volume: 45 Pages: 646-648
  • Peer Reviewed
• [Journal Article] Prevalence of Schistosoma intercalatum and S. haematobium Infection among Primary Schoolchildren in Capital Areas of Democratic Republic of Sao Tome and Principe, West Africa (2012)
  • Author(s): Chu T, et al. (他)
  • Journal Title: Iran J Parasitol Volume: 7 Pages: 67-72
  • Peer Reviewed
• [Presentation] Inositol 1,4,5-trisphosphate receptor determines intracellular Ca2+ concentration in Trypanosoma cruzi throughout its life cycle. (2016)
  • Author(s): 橋本宗明、戸井基道、呉林－国広なごみ、古川功治、茂木－平訳浩子、近江谷克裕、櫻井隆、美田敏宏、御子柴克彦、奈良武司
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市
  • Year and Date: 2016-03-19
• [Presentation] クルーズトリパノソーマに「休眠現象」は存在するのか (2016)
  • Author(s): 奈良武司、平訳浩子、角田宗一郎、細谷英里奈、三井颯太、美田敏宏．
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市
  • Year and Date: 2016-03-19
• [Presentation] Seroprevalence, environmental and behavioral risk factors of Toxocara canis infection among women in Swaziland, Southern Africa. (2016)
  • Author(s): Fan CK, Huang YH, Chou CM, Liao CW, Lee YL, Wang YC, Naito T, Tsubouchi A, Nara T.
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市
  • Year and Date: 2016-03-19
• [Presentation] Gluconeogenic compartmentalization in diplonemids, a sister group of kinetoplastids. (2016)
  • Author(s): Nara T.
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) Parasitic Disease Panel.
  • Place of Presentation: Bethesda, USA
  • Year and Date: 2016-01-13
  • Int'l Joint Research
• [Presentation] キネトプラスチダ類の特異オルガネラ、グリコソームは糖新生起原である (2015)
  • Author(s): 奈良武司、Jorge Morales、橋本宗明、Tom A. Williams、平訳浩子、牧内貴志、坪内暁子、加賀直子、高ひかり、藤村務、美田敏宏、Frederic Bringaud、Juan L. Concepcion、橋本哲男、T. Martin Embley．
  • Organizer: 第84回日本寄生虫学会大会、東京、2014
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Novel method for inducing trypomastigogenesis in vitro in Trypanosoma cruzi reveals the importance of IP3 receptor (2015)
  • Author(s): 橋本 宗明、ホルヘモラレス、御子柴克彦、奈良武司．
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Trypanosoma bruceiのシアン耐性末端酸化酵素阻害剤の解離定数と抗原虫効果 (2015)
  • Author(s): 稲岡ダニエル健、志波智夫、柘植千秋、趙理海、高橋元、上田慧、城戸康年、エマニュエルバログン、坂本君年、奈良武司、本間光貴、田仲昭子、井上将行、斎本博之、アンソニームーア、原田繁春、北潔．
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Seroprevalence, seroconversion, and toxoplasmosis risk factors among pregnant women in Taipei City, Taiwan (2015)
  • Author(s): Chia-Kwung Fan、Ching-Sheng Hung、Hung-Wen Su、Yu-Luen Lee、Hui-Wen Weng、Yin-Chin Wang、Toshio Naito、Akiko Tsubouchi、Takeshi Nara、Giueng-Chueng Wang.
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Independence from glucose-based intermediary and energy metabolisms in Diplonema papillatum, a close relative of trypanosomatids (2013)
  • Author(s): Morales J、他7名
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-29
• [Presentation] トリパノソーマの特異オルガネラ、グリコソームの起原を探る : Diplonema papillatumの解糖系酵素の一次構造と特徴 (2012)
  • Author(s): 奈良武司、他5名
  • Organizer: 第72回日本寄生虫学会東日本大会支部会第10回分子寄生虫・マラリアフォーラム合同大会
  • Place of Presentation: 前橋
  • Year and Date: 2012-10-12
• [Book] 人獣共通感染症改訂3版．木村哲、喜田宏編． (2015)
  • Author(s): 奈良武司．シャーガス病（アメリカトリパノソーマ症）
  • Total Pages: 552
  • Publisher: 医薬ジャーナル社
• [Book] トリパノソーマ症．別冊骨格筋症候群第2版上巻、日本臨牀 (2015)
  • Author(s): 奈良武司．、日本臨牀．大阪、日本臨牀社
  • Total Pages: 471
  • Publisher: 日本臨牀社
• [Book] シャーガス病（アメリカトリパノソーマ症）：人獣共通感染症 改訂3版 (2015)
  • Author(s): 奈良武司
  • Publisher: 医薬ジャーナル
• [Book] 寄生虫検査：臨床微生物検査ハンドブック (2015)
  • Author(s): 奈良武司
  • Publisher: 三輪書店
• [Book] ハリソン内科学 第4版(福井次矢、黒川清監修) (2012)
  • Author(s): 奈良武司監訳. (Part 8 感染症)
  • Total Pages: 3376
  • Publisher: メディカル・サイエンス・インターナショナル
• [Book] 岩波生物学辞典 第5版 (2012)
  • Author(s): 奈良武司執筆.(巌佐庸、倉谷滋、斎藤成也、塚谷裕一編集)
  • Total Pages: 2192
  • Publisher: 岩波書店
• [Patent(Industrial Property Rights)] トリパノソーマ関連疾患の治療薬、トリパノソーマ原虫の殺虫方法、およびその応用 (2013)
  • Inventor(s): 奈良武司、橋本宗明、御子柴克彦
  • Industrial Property Rights Holder: 奈良武司、橋本宗明、御子柴克彦
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-211448
  • Filing Date: 2013-10-08