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Study of tuberculosis latency and development of anti-tuberculosis strategy by keeping latent state

Research Project

Project/Area Number 16H05187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionNiigata University

Principal Investigator

Matsumoto Sohkichi  新潟大学, 医歯学系, 教授 (30244073)

Co-Investigator(Kenkyū-buntansha) 阿戸 学  国立感染症研究所, ハンセン病研究センター 感染制御部, 部長 (20392318)
田村 敏生  国立感染症研究所, ハンセン病研究センター 感染制御部, 室長 (40291306)
西山 晃史  新潟大学, 医歯学系, 講師 (80452069)
Research Collaborator Mekura Ryoji  
Ozeki Yuriko  
Katahira Masato  
Yamaguchi Takehiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywords結核 / ハンセン病 / 非結核性抗酸菌症 / 潜在性結核 / LTBI / 天然変性蛋白質 / ヒストン様蛋白質 / 潜伏感染 / 休眠 / 発症 / 抗酸菌 / 無症候感染 / ワクチン / 潜在性 / 潜伏 / パーシスター
Outline of Final Research Achievements

Tuberculosis is a serious health threat that kills more than 1.5 million people annually. Mycobacterium tuberculosis, an etiologic agent of tuberculosis, persistently infects one third of the human population, and 5 to 10% of them develops tuberculosis. Accordingly, prevention of the progression from latent tuberculosis is an efficient for tuberculosis control. At the latent stage M. tuberculosis is under dormant state where growth has ceased. Here we showed importance of suppression of energy production and fatty acid synthesis of mycobacteria for long term survival of mycobacterial after entering stationary phases. Our data provided reasonable basis of establishing a new control strategy against tuberculosis by deterring the disease onset.

Academic Significance and Societal Importance of the Research Achievements

細菌は無限増殖細胞であるがゆえに、その長生きについての研究は少ない。一方で、抗酸菌は分裂を停止して休眠し長期間生存する。この特徴は、抗酸菌症の経過を特徴づけている。抗酸菌の長寿の機構を、特徴的な休眠の鍵分子を足ががりとして解析した結果、霊長類の長寿とも共有するメカニズム、すなわち増殖抑制、低代謝、ラジカル抵抗性、の重要性を明かにした。本研究は、細菌から霊長類まで、真核生物に普遍的な長期生存のメカニズムが、細菌細胞でも共有されることを示した。本成果は、我々の長寿のヒントも啓示し、また難治性抗酸菌症の発生母体である無症候感染の縮小を図る革新的な制御法開発に貢献する。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (47 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (32 results) (of which Int'l Joint Research: 11 results,  Invited: 5 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] クラスノヤルスク医科大学(ロシア連邦)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ケニア中央医学研究所(ケニア)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages.2018

    • Author(s)
      Inoue M, Niki M, Ozeki Y, Nagi S, Chadeka EA, Yamaguchi T, Osada-Oka M, Ono K, Oda T, Mwende F, Kaneko Y, Matsumoto M, Kaneko S, Ichinose Y, Njenga SM, Hamano S, Matsumoto S.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 6736-6736

    • DOI

      10.1038/s41598-018-24233-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longitudinal Evaluation of Humoral Immunity and Bacterial and Clinical Parameters Reveals That Antigen-Specific Antibodies Suppress Inflammatory Responses in Active Tuberculosis Patients2018

    • Author(s)
      Niki Mamiko、Yoshiyama Takashi、Miyamoto Yuji、Okumura Masao、Niki Makoto、Oinuma Ken-ichi、Kaneko Yukihiro、Matsumoto Sohkichi、Sasaki Yuka、Ogata Hideo、Goto Hajime、Kudoh Shoji、Hoshino Yoshihiko
    • Journal Title

      Journal of Immunology Research

      Volume: 2018 Pages: 1-11

    • DOI

      10.1155/2018/4928757

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of a histone-like protein with its native structure for the diagnosis of asymptomatic tuberculosis2018

    • Author(s)
      Ohara Yukiko、Ozeki Yuriko、Tateishi Yoshitaka、Mashima Tsukasa、Arisaka Fumio、Tsunaka Yasuo、Fujiwara Yoshie、Nishiyama Akihito、Yoshida Yutaka、Kitadokoro Kengo、Kobayashi Haruka、Kaneko Yukihiro、Nakagawa Ichiro、Maekura Ryoji、Yamamoto Saburo、Katahira Masato、Matsumoto Sohkichi
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 10 Pages: 0204160-0204160

    • DOI

      10.1371/journal.pone.0204160

    • NAID

      120006534592

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] C-terminal intrinsically disordered region-dependent organization of the mycobacterial genome by a histone-like protein2018

    • Author(s)
      Savitskaya Anna、Nishiyama Akihito、Yamaguchi Takehiro、Tateishi Yoshitaka、Ozeki Yuriko、Nameta Masaaki、Kon Tomohiro、Kaboso Shaban A.、Ohara Naoya、Peryanova Olga V.、Matsumoto Sohkichi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8197-8197

    • DOI

      10.1038/s41598-018-26463-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longgitudial evaluation of humoral immunity and bacterial and clinical parameters reveals that antige-specific antibodies suppress inflammatory responses in active tuberculosis.2018

    • Author(s)
      Niki M, Yoshiyama T, Miyamoto Y, Okamura M. Niki M, Oinuma K, Kaneko Y, Matsumoto S, Sasaki Y, Ogata H, Goto H, Kudoh S, and Hoshino Y.
    • Journal Title

      J Immun Res

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions.2017

    • Author(s)
      Enany, S., Y. Yoshida, Y. Tateishi, Y. Ozeki, A. Nishiyama, A. Savitskaya, T. Yamaguchi, Y. Ohara, T. Yamamoto, M. Ato, and S. Matsumoto.
    • Journal Title

      Scientific reports

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of nutritional and ambient oxygen condition on biofilm formation in Mycobacterium avium subsp. hominissuis via altered glycolipid expression2017

    • Author(s)
      Takahiro Totani, Yukiko Nishiuchi, Yoshitaka Tateishi, Yutaka Yoshida, Hiromi Kitanaka, Mamiko Niki, Yukihiro Kaneko, Sohkichi Matsumoto
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 41775-41775

    • DOI

      10.1038/srep41775

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Meningococcal carriage rates in healthy individuals in Japan determined using Loop-Mediated Isothermal Amplification and oral throat wash specimens.2016

    • Author(s)
      Takahashi, H., M. Haga, T. Sunagawa, T. Saitoh, T. Kitahara, S. Matsumoto, and M. Ohnishi.
    • Journal Title

      Journal of infection and chemotherapy

      Volume: 22 Issue: 7 Pages: 501-504

    • DOI

      10.1016/j.jiac.2015.12.016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Long term survival and organization of the genome by the intrinsically disordered histone-like protein in mycobacteria and its application to the diagnosis of asymptomatic tuberculosis.2019

    • Author(s)
      Anna Savitskaya, Shymaa Enany, Yukiko Ohara, Akihito Nishiyama, Yuriko Ozeki, Takehiro Yamaguchi, Tsukasa Mashima, Yoshitaka Tateishi, Masaaki Nameta, Yutaka Yoshida, Shaban A. Kaboso, Haruka Kobayashi, Manabu Ato, Seigo Kitada, Ryoji Maekura, Olga V. Peryanova, Masato Katahira, and Sohkichi Matsumoto
    • Organizer
      日米医学協力計画 抗酸菌症部会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 結核の免疫2018

    • Author(s)
      松本 壮吉
    • Organizer
      第93回日本結核病学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 抗酸菌ヒストン様タンパク質による染色体制御における天然変性領域の役割2018

    • Author(s)
      西山 晃史,Anna Savitskaya ,山口 雄大,大原 直也,尾関 百合子,立石 義隆,松本 壮吉
    • Organizer
      第55回日本細菌学会中部支部総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 潜在期結核菌抗原の精製と感染診断への応用2018

    • Author(s)
      大原 由貴子,尾関 百合子,立石 義隆,真嶋 司,有坂 文雄,津中 康央,藤江 芳江,西山 晃史,吉田 豊,北所 健悟,小林 悠,金子 幸弘,中川 一路,前倉 亮治,山本 三郎,片平 正人,松本 壮吉
    • Organizer
      第55回日本細菌学会中部支部総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血清診断法開発を目指した、非結核性抗酸菌症の新規抗原の探索2018

    • Author(s)
      薄田 佑衣,立石 義隆,北田 清吾,前倉 亮治,阿戸 学,西山 晃史,尾関 百合子,松本 壮吉
    • Organizer
      第55回日本細菌学会中部支部総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of control strategies against tuberculosis based on molecular mechanism of persistence of Mycobacterium tuberculosis and host immune responses to it2018

    • Author(s)
      松本 壮吉
    • Organizer
      10TH NATIONAL CONGRESS OF INDONESIAN SOCIETY FOR CLINICAL MICROBIOLOGY
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 結核の潜在化のメカニズムとIGRAなどの結核菌感染診断について2018

    • Author(s)
      松本 壮吉
    • Organizer
      132回日本結核病学会東海地方会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mycobacterial DNA-binding protein 1 is critical for long term survival of Mycobacterium smegmatis and simultaneously coordinates cellular functions.2018

    • Author(s)
      Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, and Sohkichi Matsumoto,
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biofilm formation in Mycobaterium avium subsp. hominissuis-Role of hypoxia, eutrophy and glycopeptidolipid.2018

    • Author(s)
      Yoshitaka Tateishi, Takahiro Totani, Yukiko Nishiuchi, Yutaka Yoshida, Akihito Nishiyama, Yuriko Ozeki, Sohkichi Matsumoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Antibody responses from tuberculosis patients in Surabaya, Indonesia against Mycobacterium tuberculosis protein.2018

    • Author(s)
      Desak Nyoman Surya Suameitria Dewi, Ni Made Mertaniasih, Soedarsono4, Yuriko Ozeki, and Sohkichi Matsumoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of HIF-1α-regulated genes in Mycobacterium tuberculosis-infected macrophages.2018

    • Author(s)
      Mayuko Osada-Oka, Mutsumi Sato, Yuriko Ozeki, Sohkichi Matsumoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Whole-Genome Sequencing Analysis of Genotype Specific in Multidrug-Resistant Mycobacterium tuberculosis in Osaka Prefecture,2018

    • Author(s)
      Aki Tamaru, Takayuki Wada, Sohkichi Matsumoto, Tomotada Iwamoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A new screen for tuberculosis drug candidates utilizing a luciferase-expressing recombinant Mycobacterium bovis Bacillus Calmette-Gueren2018

    • Author(s)
      Yuriko Ozeki, Masayuki Igarashi, Matsumi Doe, Aki Tamaru, Naoko Kinoshita, Yoshitoshi Ogura, Tomotada Iwamoto, Ryuichi Sawa, Maya Umekita, Shymaa Enany, Yukiko Nishiuchi, Mayuko Osada-Oka, Tetsuya Hayashi, Mamiko Niki1,Yoshitaka Tateishi, Masaki Hatano, and Sohkichi Matsumoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effects of booster vaccine composed of MDP1 and G9.1 against tuberculosis in cynomogus monkeys.2018

    • Author(s)
      Daisuke Hayashi, Jun-ichi Maeyama, Toshiko Yamamoto, Toshio Yamazaki, Tetsu Mukai, Toshiki Tamura, Sachi Okabayashi, Fumiko Suzuki, Yuriko Ozeki, Akira Yokoyama, Yuriko Suzaki, Yasushi Ami, Yoshitaka Goto, Sumiko Iho, Sohkichi Matsumoto and Saburo Yamamoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection. (LTBI)2018

    • Author(s)
      Takeya Fujikawa, Ryoji Maekura, Seigo Kitada, Mayuko Osada-Oka, Yoshitaka Tateishi, Junko Ogawa2, Masahide Mori and Sohkichi Matsumoto.
    • Organizer
      US-Japan Cooperative Medical Science Program, 52nd Mycobacteria Panel Meeting,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 潜在期結核菌抗原の精製と感染診断への応用2018

    • Author(s)
      大原由貴子,尾関 百合子,立石 善隆,西山 晃史,山本 三郎,中川 一路,松本 壮吉
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 誘導型発現制御系を用いた抗酸菌 mycobacterial DNA- binding protein 1 の機能解析2018

    • Author(s)
      Anna Savitskaya,西山 晃史,松本 壮吉
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] From biology of Mycobacterium to the development of the control strategies against tuberculosis,2017

    • Author(s)
      Sohkichi Matsumoto
    • Organizer
      The 13th Nagasaki-Singapore Medical Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The risks for Mycobacterium tuberculosis infection2017

    • Author(s)
      松本壮吉
    • Organizer
      第51回日米医学協力計画合同会議
    • Related Report
      2016 Annual Research Report
  • [Presentation] 遅延型過敏反応から検討したMDP1 およびG9.1 からなる結核ブースターワクチン候補の免疫条件2017

    • Author(s)
      前山 順一,山崎 利雄 林 大介,山本 十糸子 尾関 百合子,鈴木 史子,山口 雄大,松本 壮吉,伊保 澄子,山本三郎
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 咽頭うがい液を用いた髄膜炎菌の健康者保菌調査の実施2017

    • Author(s)
      高橋 英之,羽賀 將衛,砂川 富正,齋藤 剛仁,北原 武尊,松本 壮吉,大西 真
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 非結核性抗酸菌のバイオフィルム形成における栄養条件とGlycopeptidolipid の役割2017

    • Author(s)
      西内 由紀子,戸谷 孝洋,立石 善隆,金子 幸弘,松本 壮吉
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 抗酸菌における誘導発現系を用いたmycobacterial DNA-bindingprotein 1 の機能解析2017

    • Author(s)
      Anna G. Savitskaya,西山 晃史,大原 直也,松本 壮吉
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 抗酸菌の長期の生存に必須な細胞機能のヒストン様タンパク質依存的な制御2017

    • Author(s)
      西山 晃史,Shymaa Enany,立石 善隆,尾関 百合子,Anna G. Savitskaya,山口 雄大,西田 由貴子,阿戸 学,松本 壮吉
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 遅延型過敏反応から検討したMDP1 およびG9.1 からなる結核ブースターワクチン候補の免疫条件2017

    • Author(s)
      前山 順一,山崎 利雄,林 大介,山本 十糸子,尾関 百合子,鈴木 史子,山口 雄大,松本 壮吉,伊保 澄子,山本三郎
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 潜在期結核菌抗原の精製と感染診断への応用2017

    • Author(s)
      西田 由貴子,尾関 百合子,立石 善隆,西山 晃史,山本 三郎,中川 一路,松本 壮吉
    • Organizer
      第90 回日本細菌学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Diagnosis fo TB infections2017

    • Author(s)
      松本 壮吉
    • Organizer
      第6回国際結核肺疾患予防連合アジア太平洋地域学術大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 非結核性抗酸菌のバイオフィルム形成における細胞壁糖脂質の役割2016

    • Author(s)
      西内 由紀子、 金子 幸弘、 松本 壮吉
    • Organizer
      第91回日本結核病学会総会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低栄養条件下における非結核性抗酸菌のバイオフィルム形成2016

    • Author(s)
      西内由紀子、戸谷孝洋、金子幸弘、松本壮吉
    • Organizer
      第30回日本バイオフィルム学会学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Morphologic analysis of the functions of the mycobacterial protein2016

    • Author(s)
      Anna Savitskaya, 西山晃史, 松本壮吉
    • Organizer
      第53回 日本細菌学会中部支部会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Biofilm formation in Mycobacterium avium subsp. hominissuis.2016

    • Author(s)
      立石善隆, 松本壮吉
    • Organizer
      第53回 日本細菌学会中部支部会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 結核・抗酸菌に特徴的な薬剤標的と新規薬剤の開発研究2016

    • Author(s)
      松本壮吉
    • Organizer
      第65回日本感染症学会東日本地方会学術集会
    • Related Report
      2016 Annual Research Report
  • [Book] シンプル微生物学(改訂第6版)2018

    • Author(s)
      松本 壮吉
    • Total Pages
      474
    • Publisher
      南江堂
    • ISBN
      4524254838
    • Related Report
      2018 Annual Research Report
  • [Book] シンプル微生物学 改訂第6版2018

    • Author(s)
      松本 壮吉 他
    • Total Pages
      7
    • Publisher
      南江堂
    • ISBN
      4524254838
    • Related Report
      2017 Annual Research Report
  • [Remarks] 新潟大学医学部細菌学教室

    • URL

      https://www.med-niigatauniv-bacteriol.org/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 新潟大学医学部細菌学教室ホームページ

    • URL

      https://www.med-niigatauniv-bacteriol.org/

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 免疫原性を有する抗酸菌蛋白質の製造方法2018

    • Inventor(s)
      尾関 百合子、西山 晃史、大原 直也、山本 三郎、松本 壮吉
    • Industrial Property Rights Holder
      新潟大学、岡山大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-107292
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2021-01-27  

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