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Analysis of the host cell death induced by the infection of Mycobacterium tuberculosis bacilli

Research Project

Project/Area Number 16K08346
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research Institution公益財団法人結核予防会 結核研究所

Principal Investigator

Takii Takemasa  公益財団法人結核予防会 結核研究所, 抗酸菌部, 主任研究員 (80244573)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords結核菌 / 細胞傷害活性 / Ⅶ型分泌装置 / カスパーゼ / パイロトーシス / 炎症性サイトカイン / 病原性 / トランスポーター / 感染症 / サイトカイン / 細胞傷害 / 抗菌ペプチド / 微生物 / 免疫学
Outline of Final Research Achievements

In this study the partial purification of cytotoxic factors was conducted from the culture filtrate of M. tuberculosis bacilli (MTB) infected human lung fibroblasts. From the mascot research using the data of LC/MS/MS analysis the several factors secreted from ESX-1, type VII secretion system encoded in RD1 region on the genome of MTB, were predicted. BCG vaccine strains, which were known to lose RD1 region, and ΔRD1 MTB showed partial cytotoxicity to human fibroblasts. These results suggested that RD1 region would be responsible to the toxicity. Next, the mechanism of the host cell death caused by MTB infection was investigated. The cytotoxicity was inhibited by caspase-1 specific inhibitor and the amount of inflammatorical cytokines in the supernatants of MTB infected cells suggested that the mechanism of the host cell death induced by MTB could be pyroptosis.

Academic Significance and Societal Importance of the Research Achievements

結核菌は他の病原体のような毒素や宿主細胞に侵入するための酵素類や運動性を持たず,その病原性についての詳細は未だ不明な点が多い.本研究では研究者が見出した結核菌感染による細胞死は生菌特異的に起こること,および,病原性のない結核ワクチン(BCG)では細胞死が誘導されないことから,結核菌の病原性の解明に繋がることが期待出来る.
得られた成果は,新たなワクチンの抗原や抗結核薬の薬剤標的として医薬品開発への貢献が期待できる.

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (39 results)

All 2020 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (27 results) (of which Int'l Joint Research: 5 results) Book (1 results)

  • [Journal Article] Tuberculous Spondylitis Caused by Intravesical Bacillus Calmette-Guerin Therapy.2020

    • Author(s)
      Minakata T, Nakano Y, Tamura S, Kazuki Y, Hayakawa K, Hayakawa T, Oota T, Fuzimoto T, Yamano Y, Takii T.
    • Journal Title

      Intern Med.

      Volume: 59(5) Pages: 733-737

    • NAID

      130007804614

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Dried Emulsion/Mannitol Composite Microparticles through a Unique Spray Nozzle for Efficient Delivery of Hydrophilic Anti-tuberculosis Drug against Alveolar Macrophages2019

    • Author(s)
      Maeda R, Ito T, Tagami T, Takii T, Ozeki T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 11 Pages: 1846-1853

    • DOI

      10.1248/bpb.b19-00368

    • NAID

      130007740634

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-11-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BCG 110 years after its conception (Institute Pasteur de Lille)に参加して2019

    • Author(s)
      瀧井猛将
    • Journal Title

      臨床と微生物

      Volume: 46(3) Pages: 82-83

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Transmission of tuberculosis and predictors of large clusters within three years in an urban setting in Tokyo, Japan: a population-based molecular epidemiological study2019

    • Author(s)
      Izumi Kiyohiko、Murase Yoshiro、Uchimura Kazuhiro、Kaebeta Aya、Ishihara Keiko、Kaguraoka Sumi、Takii Takemasa、Ohkado Akihiro
    • Journal Title

      BMJ Open

      Volume: 9 Issue: 5 Pages: e029295-e029295

    • DOI

      10.1136/bmjopen-2019-029295

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole-genome sequencing-based epidemiological analysis of anti-tuberculosis drug resistance genes in Japan in 2007: Application of the Genome Research for Asian Tuberculosis (GReAT) database.2019

    • Author(s)
      Takii T, Seki K, Wakabayashi Y, Morishige Y, Sekizuka T, Yamashita A, Kato K, Uchimura K, Ohkado A, Keicho N, Mitarai S, Kuroda M, Kato S.
    • Journal Title

      Scientific Reports

      Volume: 9(1) Issue: 1 Pages: 12823-12823

    • DOI

      10.1038/s41598-019-49219-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overcoming the pitfalls of automatic interpretation of whole genome sequencing data by online tools for the prediction of pyrazinamide resistance in Mycobacterium tuberculosis2019

    • Author(s)
      Iwamoto Tomotada、Murase Yoshiro、Yoshida Shiomi、Aono Akio、Kuroda Makoto、Sekizuka Tsuyoshi、Yamashita Akifumi、Kato Kengo、Takii Takemasa、Arikawa Kentaro、Kato Seiya、Mitarai Satoshi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 2 Pages: e0212798-e0212798

    • DOI

      10.1371/journal.pone.0212798

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 5-Hydroxy-2-methylpyridine Isolated from Cigarette Smoke Condensate Aggravates Collagen-Induced Arthritis in Mice2018

    • Author(s)
      Masafumi Takeno, Shinya Kitagawa, Junpei Yamanaka, Mayumi Teramoto, Haruka Tomita, Naohiro Shirai, Saotomo Itoh, Shigeaki Hida, Kazuichi Hayakawa, Kikuo Onozaki, Takemasa Takii
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 6 Pages: 877-884

    • DOI

      10.1248/bpb.b17-00982

    • NAID

      130007382742

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-06-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 反復配列(VNTR)分析を利用した結核菌とBCG推定の可能性2018

    • Author(s)
      前田伸司、藤原永年、山本三郎、瀧井猛将
    • Journal Title

      感染症学雑誌

      Volume: 92(5) Pages: 705-709

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of matrix metalloproteinase 9-interacting sequences in staphylococcal superantigen-like protein 5.2018

    • Author(s)
      Kohno K, Itoh S, Hanai A, Takii T, Fujiwara T, Onozaki K, Tsuji T, Hida S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 497(2) Issue: 2 Pages: 713-718

    • DOI

      10.1016/j.bbrc.2018.02.138

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 都市部における来日外国人と地域住民間の結核感染動態に関する分子疫学研究2017

    • Author(s)
      村瀬良朗、大角晃弘、渡辺ゆう、神楽岡澄、石原恵子、誉田千晶、内村和弘、前田伸司、瀧井猛将、石川信克
    • Journal Title

      結核

      Volume: 92(5) Pages: 431-439

    • NAID

      40021193511

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of the blood coagulation factor interacting sequences in staphylococcal superantigen-like protein 10.2017

    • Author(s)
      Saotomo Itoh, Takemasa Takii, Kikuo Onozaki, Tsutomu Tsuji, Shigeaki Hida
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 485 Issue: 1 Pages: 201-208

    • DOI

      10.1016/j.bbrc.2017.02.053

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 結核菌感染によるヒト肺由来線維芽細胞の細胞死とインフラマソーム活性化の関連性の解析2020

    • Author(s)
      中山真央、安田直美、谷口恵一、長谷川倫宏、大原直也、伊藤佐生智、肥田重明、小野嵜菊夫、瀧井猛将
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The cell death of lung fibroblasts by live Mycobacterium tuberculosis bacilli infection specifically induces inflammatory cytokines2019

    • Author(s)
      Takemasa Takii, Saotomo Itoh, Shigeaki Hida and Kikuo Onozaki
    • Organizer
      FEMS 2019 meeting, 8th Congress of European Microbiologist
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 結核菌によるヒト肺線維芽細胞の細胞死の解析2019

    • Author(s)
      中山真央、安田直美、谷口恵一、長谷川倫宏、田中崇裕、櫻田紳策、大原直也、 伊藤佐生智、肥田重明、小野嵜菊夫、瀧井猛将
    • Organizer
      第31回微生物シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 結核分子疫学研究における全ゲノム解析の役割2019

    • Author(s)
      瀧井猛将
    • Organizer
      第94回日本結核病学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 結核菌によるヒト肺由来線維芽細胞株における細胞死の解析2019

    • Author(s)
      中山真央、安田直美、谷口恵一、長谷川倫宏、大原直也、伊藤佐生智、肥田重明、小野嵜菊夫、瀧井猛将
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mycobacterium bovis BCG Tokyo 172 sub-type間での酸化ストレス応答の差違の解析2019

    • Author(s)
      瀧井猛将、宮竹佑治、谷口恵一、伊藤佐生智、大原直也、前山順一、林 大介、山本三郎、肥田重明、小野崎菊夫
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Comparable study between BCG Tokyo 172 type I and type II against Oxidative Stress2018

    • Author(s)
      Keiichi Taniguchi, Yuji Miyatake, Saki Suda, Daisuke Hayashi, Shouta Ogawa, Haruka Tomita, Miki Tokuda, Saburo Yamamoto, Kikuo Onozaki, Takemasa Takii
    • Organizer
      Keystone Symposia, Tuberculosis: Translating Scientific Findings for Clinical and Public Health Impact
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] アジア結核菌ゲノムデータベース(Genome Research for Asian Tuberculosis; GReAT)の構築2018

    • Author(s)
      瀧井猛将、御手洗聡、岩本朋忠、吉田志緒美、五十嵐ゆり子、近松絹代、青野昭男、慶長直人、大角晃弘、黒田誠、加藤誠也
    • Organizer
      第93回日本結核病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Contribution of arginine deiminase pathway to the acid tolerance response in Mycobacterium avium substrains avium and hominissuis2018

    • Author(s)
      Yasuhiro Horita, Saotomo Itoh, Naoya Ohara, Tetsuya Yagi, Kenji Ogawa, Shinji Maeda, Kei Nishimori, Nagatoshi Fujiwara, Yasutaka Goto, Toshio Yamazaki, Shigeaki Hida, Kikuo Onozaki, Takemasa Takii
    • Organizer
      ASM Microbe 2018 (General Meeting of American Society for Microbiology)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 結核菌遺伝子型別法の結核菌と BCG の鑑別への応用2018

    • Author(s)
      安田直美、若林靖貴、宮林亜希子、前田伸司、藤原永年、大角晃弘、山本三郎、瀧井猛将
    • Organizer
      第30回微生物シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Retrospective Study for Estimation of Mycobacterium bovis BCG Based on Variable Number Tandem Repeated Location2018

    • Author(s)
      Shinji Maeda, Nagatoshi Fujiwara, Saburo Yamamoto and Takemasa Takii
    • Organizer
      International BCG Symposium, BCG 110 years after its conception
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparable study between BCG Tokyo 172 type I and type II against Oxidative Stress2018

    • Author(s)
      Keiichi Taniguchi, Yuji Miyatake, Saki Suda, Daisuke Hayashi, Shouta Ogawa, Haruka Tomita, Miki Tokuda, Saburo Yamamoto, Kikuo Onozaki, Takemasa Takii
    • Organizer
      The 52nd US-Japan Mycobacteria Panel Meeting 2018 in Niigata, Japan.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2007 年に全国から収集した結核菌株の全ゲノム解析2018

    • Author(s)
      瀧井猛将、御手洗聡、森重雄太、加藤健吾、山下明史、関塚剛史、大角 晃弘、慶長直人、黒田誠、加藤誠也
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] BCG Rv3405c による Rv3406 の遺伝子発現抑制機構の解析2018

    • Author(s)
      白崎かおり、中山 真彰、橘 理人、山本三郎、瀧井猛将、岡部真裕子、阿戸 学、上岡 寛、大原 直也
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] TGS-TB に実装した結核菌薬剤耐性マーカーの in silico 検出ツー ルの感受性予測精度の検証2018

    • Author(s)
      山下明史、岩本朋忠、関塚剛史、村瀬良朗、加藤健吾、瀧井猛将、御手洗聡、吉田志緒美、加藤誠也、黒田誠
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Asian tubercle whole genome sequence database, "Genome Research for Asian Tuberculosis, GReAT"2017

    • Author(s)
      瀧井猛将、御手洗聡、岩本朋忠、慶長直人、吉田志緒美、土方美奈子、高木明子、関航平、若林靖貴、近松絹代、青野昭男、村瀬良朗、加藤健吾、関塚剛史、山下明史、黒田 誠、加藤誠也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 留置場における初発結核患者死亡から1年後に発覚した結核の集団感染事例2017

    • Author(s)
      前田秀雄、小林一司、小松美和、岩崎智子、高田恵理、渡瀬博俊、広松恭子、大角晃弘、村瀬良朗、瀧井猛将、石川信克
    • Organizer
      第92回結核病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
  • [Presentation] 核菌型別分析における精度保証2017

    • Author(s)
      村瀬良朗、前田伸司、岩本朋忠、瀧井猛将、御手洗聡
    • Organizer
      第92回結核病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Mycobacterium aviumの酸性環境下でのアルギニンデイミナーゼの活性化機構の解析2017

    • Author(s)
      小川翔大、山本龍二、堀田康弘、中山 真彰、大原直也、瀧井猛将
    • Organizer
      第87回実験結核研究会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
  • [Presentation] BCG Tokyo 172-1に存在するサブポピュレーションI型とII型に関する新たな知見2017

    • Author(s)
      田村庄平,白崎かおり,中山真彰,藤原永年,和田崇之,瀧井猛将,山本三郎,岡部真裕子,阿戸学,小崎弘貴,竜門亜矢子,大原直也
    • Organizer
      第87回実験結核研究会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
  • [Presentation] アジアの結核菌のゲノムデータベース”GReAT”の構築Construction of the Asian Tuberculosis whole genome sequence database, named as "GReAT"(Genome Research for Asian Tuberculosis)2017

    • Author(s)
      瀧井猛将、御手洗聡、岩本朋忠、慶長直人、吉田志緒美、土方美奈子、高木明子、関航平、若林靖貴、近松絹代、青野昭男、村瀬良朗、加藤健吾、関塚剛史、山下明史、黒田 誠、加藤誠也
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Prediction Tool for Drug-resistant Genetic Marker Based onWhole Genome Sequence of TB(結核菌全ゲノム薬剤耐性マーカー検出と感受性予測法の構築)2017

    • Author(s)
      Akifumi Yamashita, Kengo Kato, Tomotada Iwamoto, Tsuyoshi Sekizuka,Yoshiro Murase, Takemasa Takii, Satoshi Mitarai, Seiya Kato, Makoto Kuroda
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 結核菌の型別検査で実施されているVNTR法とマルチプレックス法を組み合わせた結核/BCG鑑別の試み2017

    • Author(s)
      安田直美、前田伸司、山本三郎、瀧井猛将
    • Organizer
      第171回日本結核病学会関東支部会
    • Place of Presentation
      東京
    • Year and Date
      2017-02-18
    • Related Report
      2016 Research-status Report
  • [Presentation] 結核菌生菌特異的な宿主細胞傷害活性の解析2017

    • Author(s)
      瀧井猛将、谷口恵一、長谷川倫宏、森重雄太、田中崇裕、櫻田紳策、 小野嵜菊夫
    • Organizer
      第29回微生物シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] MALDI-TOF MSを用いた迅速かつ簡便な結核菌のピラジナミド感受性試験法2017

    • Author(s)
      森重雄太、瀧井猛将
    • Organizer
      第29回微生物シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 複合オフィスビルで発生した結核集団発生事例における結核菌の全ゲノム解析2016

    • Author(s)
      村瀬良朗、大角晃弘、関塚剛史、渡部ゆう、神楽岡澄、石原恵子、誉田千晶、辰巳由里子、黒田誠、瀧井猛将、石川信克
    • Organizer
      第28回微生物シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Mycobacterium avium の酸性環境下での適応能に関する研究2016

    • Author(s)
      瀧井猛将、堀田康弘、大原直也、小川賢二、八木哲也、前田伸司、藤原永年、山崎利雄、西森 敬
    • Organizer
      第91回結核病学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2016-05-26
    • Related Report
      2016 Research-status Report
  • [Book] スタンダード薬学シリーズII 4 日本薬学会編 生物系薬学 Ⅲ.生態防御と微生物.抗酸菌、結核菌、非結核性(非定型)抗酸菌、ライ菌2016

    • Author(s)
      瀧井猛将(分担)
    • Total Pages
      242
    • Publisher
      東京化学同人
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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