Elucidation of the pathophysiology of MAC pulmonary disease focusing on bacterial cell wall lipids

• Project/Area Number: 19K08936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Keio University
• Principal Investigator: Nishimura Tomoyasu 慶應義塾大学, 保健管理センター(日吉), 講師 (90348649)
• Co-Investigator(Kenkyū-buntansha): 長谷川 直樹 慶應義塾大学, 医学部(信濃町), 教授 (20198724) ; 下田 将之 慶應義塾大学, 医学部(信濃町), 准教授 (70383734)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 非結核性抗酸菌症 / 肺MAC症 / 感染症

Outline of Research at the Start

日本において、肺非結核性抗酸菌症の約90%を占める肺Mycobacterium avium complex (MAC)症は、病態において依然不明な点が多い、難治性の慢性呼吸器感染症である。本研究では、MAC細胞壁脂質に着目し、肺MAC症の病態を解明する。MAC細胞壁脂質が肺MAC症の病態に大きく関与することが確認されれば、MAC細胞壁脂質を治療標的とした新規治療法の開発につながる可能性がある。

Outline of Final Research Achievements

To figure out the pathophysiology of Mycobacterium avium complex (MAC) pulmonary disease, which is a nontuberculous mycobacterial pulmonary disease, we studied about the biological activity of bacterial cell wall lipids, glycopeptidolipid (GPL), trehalose 6,6'-dimycolate (TDM), and trehalose 6-monomycolate (TMM). We conducted the experiments with GPL, TDM, and TMM extracted from MAC, and human macrophages. The experimental results suggested that these bacterial cell wall lipids were associated with the pathophysiology of MAC pulmonary disease.

Academic Significance and Societal Importance of the Research Achievements

日本において、肺非結核性抗酸菌症の罹患率は増加の一途をたどっており、肺非結核性抗酸菌症の内、肺MAC症が約90％を占めている。しかし、肺MAC症はその病態において依然不明な点が多い、診断が困難かつ、難治性の慢性呼吸器感染症である。本研究で、菌細胞壁脂質であるGPL、TDM、TMMの肺MAC症の病態への関与が示唆されたことから、今後、菌細胞壁脂質に着目した精度の高い検査法や治療効果の高い薬物が開発され、より良い肺MAC症診療が可能になることが期待される。

Research Products

• [Journal Article] Potential biomarker enhancing the activity of tuberculosis, hsa-miR-346. (2021)
  • Author(s): Uno S, Nishimura T, Nishio K, Kohsaka A, Tamizu E, Nakano Y, Kagyo J, Nakajima Y, Arai R, Hasegawa H, Arakawa K, Kashimura S, Ishii R, Miyazaki N, Uwamino Y, Hasegawa N.
  • Journal Title: Tuberculosis (Edinb). Volume: 129 Pages: 102101-102101
  • DOI: 10.1016/j.tube.2021.102101
  • Peer Reviewed
• [Journal Article] Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease (2021)
  • Author(s): Ho Namkoong, Yosuke Omae, Takanori Asakura, Makoto Ishii, Shoji Suzuki, Kozo Morimoto, Yosuke Kawai, Katsura Emoto, Andrew J. Oler, Eva P. Szymanski, Mitsunori Yoshida, et al.
  • Journal Title: European Respiratory Journal Volume: 57 Issue: 2 Pages: 1902269-1902269
  • DOI: 10.1183/13993003.02269-2019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease. (2021)
  • Author(s): Asakura T, Kimizuka Y, Nishimura T, Suzuki S, Namkoong H, Masugi Y, Sato Y, Ishii M, Hasegawa N.
  • Journal Title: Respirology. Volume: 26(1) Issue: 1 Pages: 112-119
  • DOI: 10.1111/resp.13886
  • Peer Reviewed
• [Journal Article] The rough colony morphotype of Mycobacterium avium exhibits high virulence in human macrophages and mice (2020)
  • Author(s): Nishimura Tomoyasu、Shimoda Masayuki、Tamizu Eiko、Uno Shunsuke、Uwamino Yoshifumi、Kashimura Shoko、Yano Ikuya、Hasegawa Naoki
  • Journal Title: Journal of Medical Microbiology Volume: 69 Issue: 7 Pages: 1020-1033
  • DOI: 10.1099/jmm.0.001224
  • Peer Reviewed
• [Journal Article] The annual risk of tuberculosis infection in newly hired researchers and healthcare workers using interferon-gamma release assay in Japan (2020)
  • Author(s): Nishimura T, Ota M, Mori M, Takano Y, Fujiwara H, Uwamino Y, Uno S, Hasegawa N.
  • Journal Title: J Infect Chemother. Volume: 26(8) Issue: 8 Pages: 818-822
  • DOI: 10.1016/j.jiac.2020.03.020
  • Peer Reviewed
• [Journal Article] Showering is associated with Mycobacterium avium complex lung disease: An observational study in Japanese women. (2020)
  • Author(s): Uwamino Y, Nishimura T, Sato Y, Tamizu E, Uno S, Mori M, Fujiwara H, Kawabe H, Murata M, Hasegawa N.
  • Journal Title: J Infect Chemother. Volume: 26(3) Issue: 3 Pages: 211-214
  • DOI: 10.1016/j.jiac.2019.09.003
  • Peer Reviewed
• [Journal Article] Effect of refrigeration of blood samples in lithium-heparin tubes on QuantiFERON TB Gold Plus test result. (2020)
  • Author(s): Uwamino Y, Sakai A, Nishimura T, Noguchi M, Uno S, Fujiwara H, Mori M, Wakui M, Murata M, Hasegawa N.
  • Journal Title: J Infect Chemother. Volume: 26(3) Issue: 3 Pages: 312-314
  • DOI: 10.1016/j.jiac.2019.10.002
  • Peer Reviewed
• [Journal Article] Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease. (2019)
  • Author(s): Kimizuka Y, Hoshino Y, Nishimura T, Asami T, Sakakibara Y, Morimoto K, Maeda S, Nakata N, Abe T, Uno S, Namkoong H, Fujiwara H, Funatsu Y, Yagi K, Fujie T, Ishii M, Inase N, Iwata S, Kurashima A, Betsuyaku T, Hasegawa N; Non-Tuberculous Mycobacteriosis-Japan Research Consortium (NTM-JRC).
  • Journal Title: PLoS One. Volume: 14(4) Issue: 4 Pages: e0216034-e0216034
  • DOI: 10.1371/journal.pone.0216034
  • Peer Reviewed / Open Access
• [Journal Article] Sitafloxacin-Containing Regimen for the Treatment of Refractory?Mycobacterium avium?Complex Lung Disease. (2019)
  • Author(s): Asakura T, Suzuki S,Fukano H, Okamori S, Kusumoto T, Uwamino Y, Ogawa T, So M, Uno S, Namkoong H, Yoshida M, Kamata H, Ishii M, Nishimura T, Hoshino Y, Hasegawa N.
  • Journal Title: Open forum infectious diseases Volume: 6 Issue: 4
  • DOI: 10.1093/ofid/ofz108
  • Peer Reviewed / Open Access
• [Journal Article] Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study. (2019)
  • Author(s): Uwamino Y, Nishimura T, Sato Y, Tamizu E, Asakura T, Uno S, Mori M, Fujiwara H, Ishii M, Kawabe H, Murata M, Hasegawa N.
  • Journal Title: BMC Infect Dis. Volume: 19(1) Issue: 1 Pages: 1055-1055
  • DOI: 10.1186/s12879-019-4668-x
  • Peer Reviewed / Open Access
• [Presentation] 外国人留学生の感染症対策 結核対策を中心として (2021)
  • Author(s): 西村知泰
  • Organizer: 第19回日本旅行医学会大会
  • Invited
• [Presentation] 抗酸菌の宿主免疫 マクロファージなどのinnate immunityと抗酸菌感染 (2021)
  • Author(s): 西村知泰
  • Organizer: 第96回日本結核・非結核性抗酸菌症学会総会・学術講演会
  • Invited
• [Presentation] 肺非結核性抗酸菌症の疾患活動性の指標(バイオマーカー)について (2020)
  • Author(s): 西村知泰
  • Organizer: 第95回日本結核・非結核性抗酸菌症学会総会・学術講演会
  • Invited
• [Presentation] 医療従事者の入職健診でIGRAはまだ必要か Proの立場から (2020)
  • Author(s): 西村知泰
  • Organizer: 第95回日本結核・非結核性抗酸菌症学会総会・学術講演会
  • Invited
• [Presentation] QuantiFERON TBゴールドプラスの検体のヘパリン管採血と,その冷蔵保存による検査結果への影響 (2020)
  • Author(s): 酒井昭子，上蓑義典，西村知泰，森正明，宇野俊介，藤原宏，村田満，長谷川直樹．
  • Organizer: 第31回日本臨床微生物学会総会・学術集会
• [Presentation] 外国人留学生を対象とした結核感染調査 (2019)
  • Author(s): 西村知泰，森正明，和井内由充子，広瀬寛，牧野伸司，横山裕一，武田彩乃，畔上達彦，後藤伸子，河邊博史．
  • Organizer: 第116回日本内科学会総会・講演会
• [Presentation] 閉経後女性における血清エストラジオール低値と肺Mycobacterium avium complex感染症の関連性 (2019)
  • Author(s): 上蓑義典，西村知泰，宇野俊介，森正明，長谷川直樹，佐藤泰憲，田水映子，村田満．
  • Organizer: 第94回日本結核病学会総会