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Comprehensive and rapid diagnosis of non-tuberculous mycobacterial pulmonary disease by using multi-locus sequence typing

Research Project

Project/Area Number 21K08194
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionOsaka Toneyama Medical Center

Principal Investigator

Kida Hiroshi  独立行政法人国立病院機構大阪刀根山医療センター(臨床研究部), 独立行政法人国立病院機構大阪刀根山医療センター, 呼吸器内科部長 (80512988)

Co-Investigator(Kenkyū-buntansha) 福島 清春  大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00752156)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsMGIT-seq法 / NALC-seq法 / MLST法 / mlstverse / target capture sequence / マクロライド耐性肺MAC症 / MGIT-seq / NALC-seq / Mycobacterium gordonae / 新種 / マクロライド耐性 / MLST / 非結核性抗酸菌 / 菌種同定 / 薬剤感受性 / 亜種 / ツカムレラ / 肺非結核性抗酸菌症 / 迅速診断
Outline of Research at the Start

本研究の概要は、大阪大学微生物病研究所遺伝情報実験センター感染症メタゲノム研究分野、中村らと共同で、メタゲノム解析による肺非結核性抗酸菌症の迅速かつ網羅的診断システム“刀根山モデル”の開発を開始し、喀痰採取より3時間以内に175種のNTM菌同定を目指し、最適化を進める研究である。さらにこの手法を用いて、臨床検査における同定不能菌の新規同定を行い肺非結核性抗酸菌疫学の実態を明らかにするとともに、臨床的難治症例(治療失敗、再発)における問題点も明らかにする。

Outline of Final Research Achievements

In the treatment of NTM pulmonary disease (PD), species identification and drug susceptibility testing following sputum acid-fast bacillus culture involve complex procedures that are labor-intensive and time-consuming. The primary objective of this research project was to position the newly developed comprehensive NTM species identification system (mlstverse) within the clinical practice of NTM PD treatment. We linked mlstverse with liquid culture (MGIT-seq) and demonstrated the utility of the MGIT-seq method, which includes drug susceptibility prediction, in a prospective clinical trial. Additionally, we discovered five new NTM species using the mlstverse method. Furthermore, we successfully developed the NALC-seq method, which allows for direct species identification from sputum specimens treated with NALC without the need for culture.

Academic Significance and Societal Importance of the Research Achievements

MGIT-seq法は抗酸菌菌種同定、薬剤感受性検査を精緻化、時短化するだけでなく、検査技師人材不足に悩む病院でもインターネットに接続可能なら実施可能であるため、肺NTM症診療の均てん化に貢献する。また省力化によって、全ての病院で抗酸菌菌種同定、薬剤感受性検査が普及し、例えばマクロライド耐性可塑性など、感染症学における重要なテーマを提供するようになる。mlstverseによる新種発見が細菌学の裾野を拡げることは言うまでもない。NALC-seq法による培養を経ない菌種同定検査法はさらなる時短化とともに培養検査よるバイアスフリーの気道感染菌情報を提供し、呼吸器感染症学におけるブレークスルーを起こす。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] Diagnosis and management of drug-induced interstitial lung disease associated with amikacin liposome inhalation suspension in refractory Mycobacterium avium complex pulmonary disease: a case report2023

    • Author(s)
      Hashimoto K, Nii T, Sumitani H, Yokoyama M, Miyamoto S, Mihashi Y, Nagata Y, Matsuki T, Tsujino K, Miki K, Kida H
    • Journal Title

      Infection and Drug Resistance

      Volume: 16 Pages: 6629-6634

    • DOI

      10.2147/idr.s427544

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Invariant natural killer T cells and iron metabolism orchestrate skin development and homeostasis2023

    • Author(s)
      Nabeshima H, Niitsu T, Fukushima K, Kida H
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 20 Issue: 10 Pages: 1095-1097

    • DOI

      10.1038/s41423-023-01016-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identifying phenotypes in interstitial lung disease using group-based trajectory modelling2023

    • Author(s)
      Takata S.、Komukai S.、Hoshino T.、Tabuchi H.、Masuhiro K.、Yaga M.、Shirai Y.、Mitsui Y.、Abe Y.、Kuge T.、Fukushima K.、Kida H.、Kumanogoh A.
    • Journal Title

      The International Journal of Tuberculosis and Lung Disease

      Volume: 27 Issue: 4 Pages: 332-334

    • DOI

      10.5588/ijtld.22.0417

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MGIT-seq for the Identification of Nontuberculous Mycobacteria and Drug Resistance: a Prospective Study2023

    • Author(s)
      Fukushima K、Matsumoto Y、Matsuki T、Saito H、Motooka D、Komukai S、Fukui E、Yamuchi J、Nitta T、Niitsu T、Abe Y、Nabeshima H、Nagahama Y、Nii T、Tsujino K、Miki K、Kitada S、Kumanogoh A、Akira S、Nakamura S、Kida H
    • Journal Title

      Journal of Clinical Microbiology

      Volume: 61 Issue: 4

    • DOI

      10.1128/jcm.01626-22

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-world impact of antifibrotics on prognosis in patients with progressive fibrosing interstitial lung disease2023

    • Author(s)
      Niitsu Takayuki、Fukushima Kiyoharu、Komukai Sho、Takata So、Abe Yuko、Nii Takuro、Kuge Tomoki、Iwakoshi Shinichi、Shiroyama Takayuki、Miyake Kotaro、Tujino Kazuyuki、Tanizaki Satoshi、Iwahori Kota、Hirata Haruhiko、Miki Keisuke、Yanagawa Masahiro、Takeuchi Noriyuki、Takeda Yoshito、Kida Hiroshi、Kumanogoh Atsushi
    • Journal Title

      RMD Open

      Volume: 9 Issue: 1 Pages: e002667-e002667

    • DOI

      10.1136/rmdopen-2022-002667

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Diagnosis of Nontuberculous Mycobacterial Pulmonary Disease by Single Bacterial Isolation Plus Anti-GPL-Core IgA Antibody2022

    • Author(s)
      Kawasaki Takahiro、Kitada Seigo、Fukushima Kiyoharu、Akiba Eri、Haduki Kako、Saito Haruko、Nitta Tadayoshi、Kawano Akira、Miyazaki Akito、Nii Takuro、Kuge Tomoki、Koba Taro、Matsuki Takanori、Tsujino Kazuyuki、Miki Keisuke、Maekura Ryoji、Kida Hiroshi
    • Journal Title

      Microbiology Spectrum

      Volume: 10 Issue: 1

    • DOI

      10.1128/spectrum.01406-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific targeting of lung ILC2s via NRP1 in pulmonary fibrosis2022

    • Author(s)
      Nii Takuro、Fukushima Kiyoharu、Kida Hiroshi
    • Journal Title

      Cellular & Molecular Immunology

      Volume: 19 Issue: 8 Pages: 869-871

    • DOI

      10.1038/s41423-022-00867-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mycobacterium senriense sp. nov., a slowly growing, non-scotochromogenic species, isolated from sputum of an elderly man2022

    • Author(s)
      Abe Yuko、Fukushima Kiyoharu、Matsumoto Yuki、Niitsu Takayuki、Nabeshima Hiroshi、Nagahama Yasuharu、Akiba Eri、Haduki Kako、Saito Haruko、Nitta Tadayoshi、Kawano Akira、Tanaka Michio、Matsuki Takanori、Motooka Daisuke、Tsujino Kazuyuki、Miki Keisuke、Nakamura Shota、Iida Tetsuya、Kida Hiroshi
    • Journal Title

      International Journal of Systematic and Evolutionary Microbiology

      Volume: 72 Issue: 5 Pages: 005378-005378

    • DOI

      10.1099/ijsem.0.005378

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic Pulmonary Disease Caused by <i>Tsukamurella toyonakaense</i>2022

    • Author(s)
      Kuge Tomoki、Fukushima Kiyoharu、Matsumoto Yuki、Saito Haruko、Abe Yuko、Akiba Eri、Haduki Kako、Nitta Tadayoshi、Kawano Akira、Tanaka Michio、Hattori Yumi、Kawasaki Takahiro、Matsuki Takanori、Shiroyama Takayuki、Motooka Daisuke、Tsujino Kazuyuki、Miki Keisuke、Mori Masahide、Kitada Seigo、Nakamura Shota、etc
    • Journal Title

      Emerging Infectious Diseases

      Volume: 28 Issue: 7 Pages: 1437-1441

    • DOI

      10.3201/eid2807.212320

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum GPL core antibody levels are associated with disease activity and treatment outcomes in Mycobacterium avium complex lung disease following first line antibiotic treatment2021

    • Author(s)
      Fukushima Kiyoharu、Kitada Seigo、Matsumoto Yuki、Komukai Sho、Kuge Tomoki、Kawasaki Takahiro、Matsuki Takanori、Motooka Daisuke、Tsujino Kazuyuki、Miki Mari、Miki Keisuke、Nakamura Shota、Kida Hiroshi
    • Journal Title

      Respiratory Medicine

      Volume: 187 Pages: 106585-106585

    • DOI

      10.1016/j.rmed.2021.106585

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pleural Effusion Caused by Mycolicibacterium mageritense in an Immunocompetent Host: A Case Report2021

    • Author(s)
      Niitsu Takayuki、Kuge Tomoki、Fukushima Kiyoharu、Matsumoto Yuki、Abe Yuko、Okamoto Masashi、Haduki Kako、Saito Haruko、Nitta Tadayoshi、Kawano Akira、Matsuki Takanori、Motooka Daisuke、Tsujino Kazuyuki、Miki Keisuke、Nakamura Shota、Kida Hiroshi、Kumanogoh Atsushi
    • Journal Title

      Frontiers in Medicine

      Volume: 8

    • DOI

      10.3389/fmed.2021.797171

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Advances and Challenges of Antibody Therapeutics for Severe Bronchial Asthma2021

    • Author(s)
      Abe Yuko、Suga Yasuhiko、Fukushima Kiyoharu、Ohata Hayase、Niitsu Takayuki、Nabeshima Hiroshi、Nagahama Yasuharu、Kida Hiroshi、Kumanogoh Atsushi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 1 Pages: 83-83

    • DOI

      10.3390/ijms23010083

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肺非結核性抗酸菌症の診断基準を見直す2023

    • Author(s)
      木田博
    • Organizer
      第63回日本呼吸器学会学術講演会
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Invited
  • [Presentation] リアルタイムコアゲノム解析による非結核性抗酸菌症の迅速・高精度同定法の確立および臨床応用2023

    • Author(s)
      松木隆典、福島清春、松本悠希、橋本和樹、新居卓朗、元岡大佑、辻野和之、三木啓資、中村昇太、木田博
    • Organizer
      第63回日本呼吸器学会学術講演会
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Presentation] マクロライド耐性肺Mycobacterium avium complex症における耐性化の可塑性と治療選択2023

    • Author(s)
      安部祐子、福島清春、松本悠希、北田清悟、元岡大佑、新津敬之、新居卓朗、松木隆典、熊ノ郷淳、中村昇太、木田博
    • Organizer
      第63回日本呼吸器学会学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 同定不能抗酸菌と誤同定された新種のTsukamurella toyonakaenseによる慢性肺感染症の一例2023

    • Author(s)
      久下朋輝、福島清春、安部祐子、川崎貴裕、松木隆典、白山敬之、辻野和之、三木啓資、森雅秀、北田清悟、木田博、熊ノ郷淳
    • Organizer
      第63回日本呼吸器学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肺Mycobacterium abscessus complex症(肺MABC症)における抗GPL-core IgA抗体の陽性率及び臨床像2023

    • Author(s)
      新居卓朗、福島清春、住谷仁、横山将史、橋本和樹、松木隆典、辻野和之、三木啓資、木田博
    • Organizer
      第63回日本呼吸器学会学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] 次世代シーケンサーMinIONを用いた抗酸菌リアルタイム同定システムの開発2022

    • Author(s)
      松本悠希、福島清春、元岡大祐、金城武士、木田博、中村昇太
    • Organizer
      第97回日本結核・非結核性抗酸菌症学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] リアルタイムコアゲノム解析による非結核性抗酸菌症の迅速・高精度同定法の確立および臨床応用2022

    • Author(s)
      新津敬之、福島清春、松本悠希、安部祐子、新居卓朗、木庭太郎、松木隆典、元岡大祐、辻野和之、三木啓資、中村昇太、木田博
    • Organizer
      第62回日本呼吸器学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] リアルタイムコアゲノム解析による非結核性抗酸菌症の迅速・高精度同定法の確立および臨床応用2021

    • Author(s)
      安部祐子、福島清春、松本悠希、新津敬之、新居卓朗、木庭太郎、松木隆典、元岡大祐、辻野和之、三木啓資、中村昇太、木田博
    • Organizer
      第41回日本サルコイーシス/肉芽腫性疾患学会総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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