Modification of host immunity by mycobacteria : role of cell wall glycolipids

• Project/Area Number: 20590441
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Osaka University
• Principal Investigator: MORITA Yasuhiro Osaka University, 微生物病研究所, 助教 (70397769)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 感染免疫 / マイコバクテリア / 細胞壁 / 糖脂質

Research Abstract

Cell wall glycolipids of mycobacteria have been suggested to be important for host immune modulation. In this study, we first clarified the importance of controlling the expression levels of two glycosyltransferases involved in the biosynthesis of these glycolipids. We then revealed that the structural alterations of these glycolipids make both Mycobacterium smegmatis and Mycobacterium tuberculosis vulnerable in terms of cell wall permeability. In addition, we demonstrated the presence of phosphatidylinositol 3-phosphate in Mycobacterium smegmatis for the first time.

Research Products

• [Journal Article] Inositol lipid metabolism in mycobacteria : biosynthesis and regulatory mechanisms. (2011)
  • Author(s): Morita, Y.S., Fukuda, T., Sena, C.B., Yamaryo-Botte, Y., McConville, M.J., Kinoshita, T.
  • Journal Title: Biochim. Biophys. Acta, in press
  • Peer Reviewed
• [Journal Article] Stress-induced synthesis of phosphatidylinositol 3-phosphate in mycobacteria. (2010)
  • Author(s): Morita, Y.S., Yamaryo-Botte, Y., Miyanagi, K., Callaghan, J.M., Patterson, J.H., Crellin, P.K., Coppel, R.L., Billman-Jacobe, H., Kinoshita, T., McConville, M.J.
  • Journal Title: J.Biol. Chem. 285 Pages: 16643-50
  • Peer Reviewed
• [Journal Article] Controlled expression of branch-forming mannosyltransferase is critical for mycobacterial lipoarabinomannan biosynthesis. (2010)
  • Author(s): Sena, C.B., Fukuda, T., Miyanagi, K., Matsumoto, S., Kobayashi, K.,Murakami, Y., Maeda, Y., Kinoshita, T., Morita, Y.S.
  • Journal Title: J.Biol. Chem. 285 Pages: 13326-36
  • Peer Reviewed
• [Journal Article] Controlled expression of branch-forming mannosyltransferase is critical for mycobacterial lipoarabinomannan biosynthesis (2010)
  • Author(s): Chubert B.C.Sena, et.al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 13326-13336
  • Peer Reviewed
• [Journal Article] Stress-induced synthesis of phosphatidylinositol 3-phosphate in mycobacteria (2010)
  • Author(s): Yasu S.Morita, et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 16643-50
  • Peer Reviewed
• [Journal Article] Controlled expression of branch-forming mannosyltransferase is critical for mycobacterial lipoarabinomannan biosynthesis (2010)
  • Author(s): Chubert B.C.Sena, et. al.
  • Journal Title: J.Biol.Chem. (in press)
  • Peer Reviewed
• [Journal Article] Direct recognition of the mycobacterial glycolipid, trehalosedimycolate, by C-type lectin Mincle : Mincle isareceptor formycobacterial glycolipid. (2009)
  • Author(s): Ishikawa, E., Ishikawa, T., Morita, Y.S., Toyonaga, K., Yamada, H., Takeuchi, O., Kinoshita, T., Akira, S., Yoshikai, Y., Yamasaki, S.
  • Journal Title: J.Exp. Med. 206 Pages: 2879-88
  • Peer Reviewed
• [Journal Article] Mutations in pimE restore lipoarabinomannan synthesis and growth in a Mycobacterium smegmatislpqW mutant. (2008)
  • Author(s): Crellin, P.K., Kovacevic, S., Martin, K.L., Brammananth, R., Morita, Y.S., Billman-Jacobe, H., McConville, M.J., Coppel, R.L.
  • Journal Title: J.Bacteriol. 190 Pages: 3690-3699
  • Peer Reviewed
• [Presentation] Structural alterations of lipomannan and lipoarabinomannanaffect the integrity of mycobacterialcell wall. (2011)
  • Author(s): Fukuda, T., Miyanagi, K., Hamasaki, M., Yoshimori, T., Murakami, Y., Maeda, Y., Kinoshita, T., Morita, Y.S.
  • Organizer: Keystone Symposia of Molecular and Cellular Biology : Mycobacteria : Physiology, Metabolism and Pathogenesis. Back to the Basics
  • Place of Presentation: Vancouver Canada
  • Year and Date: 2011-05-17
• [Presentation] Structural alterations of lipomannan and lipoarabinomannan affect the integrity of mycobacterial cell wall (2011)
  • Author(s): Fukuda, T., et al.
  • Organizer: Keystone Symposia : Mycobacteria : Physiology, Metabolism and Pathogenesis-Back to the Basics
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2011-01-17
• [Presentation] Stress-inducedsynthesis of phosphatidylinositol3-phosphate in mycobacteria. (2010)
  • Author(s): Morita, Y.S., Yamaryo-Botte, Y., Miyanagi, K., Crellin, P., Coppel, R.L., Kinoshita, T., McConville, M.J.
  • Organizer: OzBio2010 (incorporating the 12th IUBMB conference).
  • Place of Presentation: Melbourne,Australia
  • Year and Date: 2010-12-30
• [Presentation] The effects of structural alterations oflipomannan and lipoarabinomannan on mycobacterial cell wall. (2010)
  • Author(s): Fukuda, T., Miyanagi, K., Hamasaki, M., Yoshimori, T., Maeda, Y., Kinoshita,T., Morita, Y.S.
  • Organizer: The 83rdAnnual Meeting of the Japanese Biochemical Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-12-09
• [Presentation] The effects of structural alterations of lipomannan and lipoarabinomannan on mycobacterial cell wall (2010)
  • Author(s): Fukuda, T., et al.
  • Organizer: The 83rd Annual Meeting of the Japanese Biochemical Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-12-09
• [Presentation] Accumulation ofan unknown product and effects on cell growth by inhibitinglipoarabinomannan biosynthesis inmycobacteria. (2010)
  • Author(s): Fukuda, T., Maeda, Y., Kinoshita, T., Morita, Y.S.
  • Organizer: The 82nd Annual Meeting of the Japanese Biochemical Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-10-21
• [Presentation] Stress-induced synthesis of phosphatidylinositol 3-phosphate in mycobacteria (2010)
  • Author(s): Morita, Y.S., et al.
  • Organizer: OzBio2010 (and the 12th IUBMB conference)
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2010-09-30
• [Presentation] Controlledexpression of branch-formingmannosyltransferase is critical forthe biosynthesis of lipoarabinomannan in mycobacteria. (2010)
  • Author(s): Sena, C.B., Fukuda, T., Miyanagi, K., Matsumoto, S., Kobayashi, K., Murakami, Y., Maeda, Y., Kinoshita, T., Morita, Y.S.
  • Organizer: XXVth International Carbohydrate Symposium
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2010-08-05
• [Presentation] Controlled expression of branch-forming mannosyltransferase is critical for the biosynthesis of lipoarabinomannan in mycobacteria (2010)
  • Author(s): Sena, C.B., et al.
  • Organizer: XXVth International Carbohydrate Symposium
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2010-08-05
• [Presentation] Stress-induced biosynthesis of phosphatidylinositol 3-phosphate inmycobacteria. (2010)
  • Author(s): Morita, Y.S., Kinoshita, T.
  • Organizer: The 83rd Annual Meeting of the Japanese Society for Bacteriology
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-03-28
• [Presentation] Inhibition of LAM biosynthesis accumulates a LM-like product and affects mycobacterial proliferation. (2010)
  • Author(s): Fukuda, T., Kinoshita, T., Morita, Y.S.
  • Organizer: The 83rd Annual Meeting of the Japanese Society forBacteriology
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-03-28
• [Presentation] Compartmentalization of glycolipid biosynthesis in mycobacteria. (2009)
  • Author(s): Morita, Y.S., Fukuda, T., Maeda, Y., Kinoshita, T.
  • Organizer: The First International Kishimoto Foundation Symposium "Immune Regulation : Present and Future"
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2009-05-25
• [Presentation] Identification ofphosphatidylinositol 3-phosphate inmycobacteria. (2009)
  • Author(s): Morita, Y.S., Kinoshita, T.
  • Organizer: The 82nd Annual Meeting of the Japanese Society forBacteriology.
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2009-03-13
• [Presentation] Effect ofsuppressed lipoarabinomannan biosynthesis onmycobacterial growth. (2009)
  • Author(s): Fukuda, T., Kinoshita, T., Morita, Y.S.
  • Organizer: The 82nd AnnualMeeting of the Japanese Society forBacteriology.
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2009-03-13
• [Presentation] Subcellular localization of enzymes involved in the biosynthesis of GPI-like glycolipids in mycobacteria. (2008)
  • Author(s): Fukuda, T., Maeda, Y., Kinoshita, T., Morita, Y.S.
  • Organizer: The 81st Annual Meeting ofthe Japanese Biochemical Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2008-12-10
• [Presentation] Compartmentalization of glycolipid biosynthesis in mycobacteria. (2008)
  • Author(s): Morita, Y.S., Nakatani, F., McMillan, B.N.I., Billman-Jacobe, H.,McConville, M.J., Maeda, Y., Kinoshita, T.
  • Organizer: Human Frontier Science Program 8th Annual Awardees Meeting
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-07-07
• [Presentation] Mannosyltransferase required for α1,2-mannosylation of lipomannan and lipoarabinomannan in Mycobacterium bovis bacillus Calmette-Guerin. (2008)
  • Author(s): Sena, C.B., Matsumoto, S., Kobayashi, K., McConville, M.J., Maeda, Y., Kinoshita, T., Morita, Y.S.
  • Organizer: The Seventh International Conference on the Pathogenesis of MycobacterialInfections
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2008-06-27
• [Presentation] Subcellular compartmentalization of membrane-bound enzymes involved inthe synthesis of phosphatidylinositolmannosides in Mycobacterium smegmatis. (2008)
  • Author(s): Morita, Y.S., Fukuda, T., Billman-Jacobe, H., McConville, M.J., Maeda, Y., Kinoshita, T.
  • Organizer: The Seventh International Conference on the Pathogenesis of Mycobacterial Infections
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2008-06-27
• [Presentation] Mannosyl transferase reauired for al, 2-mannosylation oflipofflannan and lipoarabinomannan in Mycobacterium bovisbacillus Calmet te-Guerin (2008)
  • Author(s): Chubert B. C. Sena
  • Organizer: Seventh International Conference on the Pathogenes is of Mycobacterial Infections
  • Place of Presentation: スウェーデン国ストックホルム市
  • Year and Date: 2008-06-27
• [Book] Achapterin "The Enzymes, Volume 26, Glycosylphosphatidylinositol(GPI) Anchoring of Proteins". (Menon,A.K., Kinoshita, T., Orlean, P., Tamanoi, F., Editors) Academic Press. (2009)
  • Author(s): Maeda, Y., Morita, Y.S.
  • Publisher: Mannosylation.
• [Remarks] ホームページ等
  • URL: http://www.biken.osaka-u.ac.jp/biken/men-eki-huzen/index.html
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/biken/men-eki-huzen/index.html