Biogenesis of lamellar body-like organelles in host cells expressing Mycobacterium tuberculosis PE_PGRS62

• Project/Area Number: 15K19102
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Iwai Hiroki 国立研究開発法人国立国際医療研究センター, その他部局等, 研究員(移行) (70443116)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 結核菌 / M. tuberculosis / PE_PGRS62 / ABCA3 / lamellar body

Outline of Final Research Achievements

PE_PGRS62 is a member of the M. tuberculosis PE_PGRS family of glycine-rich proteins, and thought to be a virulent factor. We described here that two type II alveolar epithelial cell (AEC II)-like cell lines, A549 and T7, expressing GFP-PE_PGRS62 possessed lamellar body-like vesicles. The vesicles contained lipid with multi-membrane structures. PE_PGRS62 was co-localized on the vesicles with the ATP-binding cassette transporter ABCA3, a marker of a lamellar body limiting membrane of AEC II. These results suggest that PE_PGRS62 generates lamellar body-like vesicles containing lipid in AEC II.

Research Products

• [Journal Article] Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis. (2016)
  • Author(s): Matsumura K, Iwai H, Kato-Miyazawa M, Kirikae F, Zhao J, Yanagawa T, Ishii T, Miyoshi-Akiyama T, Funatogawa K, Kirikae T.
  • Journal Title: Journal of Immunology Volume: 197(8) Pages: 3233-3244
  • Peer Reviewed
• [Journal Article] A mutation in the decoding region of 16S rRNA attenuates the virulence of Mycobacterium tuberculosis. (2016)
  • Author(s): Watanabe, S., Matsumura, K., Iwai, H., Funatogawa, K., Haishima, Y., Fukui, C., Okumura, K., Kato, M., Hashimoto, M., Teramoto, K., Kirikae, F., Miyoshi-Akiyama, T., and Kirikae, T.
  • Journal Title: Infection and Immunity. Volume: 84 Issue: 8 Pages: 2264-2273
  • DOI: 10.1128/iai.00417-16
  • Peer Reviewed / Open Access
• [Journal Article] CASTB (the comprehensive analysis server for the Mycobacterium tuberculosis complex): A publicly accessible web server for epidemiological analyses, drug-resistance prediction and phylogenetic comparison of clinical isolates. (2015)
  • Author(s): Iwai H, Kato-Miyazawa M, Kirikae T, Miyoshi-Akiyama T.
  • Journal Title: Tuberculosis (Edinb) Volume: 95(6) Issue: 6 Pages: 843-4
  • DOI: 10.1016/j.tube.2015.09.002
  • Peer Reviewed
• [Presentation] Analysis of PRDX1 which contributes to host defenses against Mycobacterium tuberculosis (2017)
  • Author(s): 松村 和典，祝 弘樹，加藤-宮澤 雅子，切替 富美子，趙 吉子，柳川 徹，石井 哲郎，舩渡川 圭次，秋山 徹，切替 照雄
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際センター展示棟
  • Year and Date: 2017-03-19
• [Presentation] カナマイシン耐性に寄与する16SリボゾームRNA の解読領域の 変異と結核菌の弱毒化 (2017)
  • Author(s): 渡邊 真弥，松村 和典，祝 弘樹，舩渡川 圭次，加藤 雅 子，切替 富美子，秋山 徹，崔 龍洙，切替 照雄
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際センター展示棟
  • Year and Date: 2017-03-19
• [Presentation] A Mutation in the 16S rRNA Decoding Region Attenuates the Virulence of Mycobacterium tuberculosis (2017)
  • Author(s): Shinya Watanabe, Kazunori Matsumura, Hiroki Iwai, Keiji Funatogawa, Yuji Haishima, Chie Fukui, Kayo Okumura, Masako Kato-Miyazawa, Masahito Hashimoto, Kanae Teramoto, Fumiko Kirikae, Tohru Miyoshi-Akiyama, Teruo Kirikae
  • Organizer: Keystone Symposia, New Developments in Our Basic Understanding of Tuberculosis (A5)
  • Place of Presentation: Fairmont Hotel Vancouver, Vancouver, Brithish Columbia, Canada
  • Year and Date: 2017-01-14
  • Int'l Joint Research
• [Presentation] A mycobacterial virulence protein, PE_P GRS62, inhibits autophagy in macrophage s (2016)
  • Author(s): Hiroki Iwai, Kazunori Matsumura, Fumiko Kirikae, Jeffery Cox, Keiji Funatogawa, Toru Miyoshi-Akiyama, Teruo Kirikae
  • Organizer: The 24th International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: Sola City Conference Center
  • Year and Date: 2016-06-04
  • Int'l Joint Research
• [Presentation] Rv3812-encoded PE_PGRS62 protein is surface-exposed in tubercle bacilli (2016)
  • Author(s): Hiroki Iwai, Miwa Tamura-Nakano, Kazunori Matsumura, Yuji Miyamoto, Tetsu Mukai, Masahiko Makino, Cox Jeffery, Keiji Funatogawa, Toru Miyoshi-Akiyama, Teruo Kirikae
  • Organizer: 第８９回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2016-03-23