The host-pathogen interaction controlled by MAC glycopeptidolipid

• Project/Area Number: 25460543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Tezukayama University
• Principal Investigator: Fujiwara Nagatoshi 帝塚山大学, 現代生活学部, 教授 (80326256)
• Co-Investigator(Kenkyū-buntansha): 綾田 稔 大阪市立大学, 大学院医学研究科, 准教授 (90222702)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 非結核性抗酸菌症 / 宿主応答 / 糖ペプチド異質 / glycopeptidolipid / 糖ペプチド脂質 / M. intracellulare

Outline of Final Research Achievements

Mycobacterium avium-intracellulare complex (MAC) is the most common pathogen of nontuberculous mycobacteria which causes pulmonary disease. MAC species are classified 28 serotypes according to the species-specific glycopeptidolipid (GPL) antigen. In this study, we identified a novel GPL in structure and biosynthesis gene cluster from clinical isolate. The host recognition of GPLs by toll-like receptor-2 (TLR2) was escaped by the position of acetyl groups in the oligosaccharide. On the other hand, Mycobacterium smegmatis J15cs strain deleted GPLs by the mutation of mps1 gene. The bacterial morphology of J15cs strain changed the rough type from smooth type, and can survived longer in the host cells. These results implied that serotype-specific GPLs play important roles in MAC infections and pathogenesis.

Research Products

• [Int'l Joint Research] School of Biosciences/University of Birmingham(United Kingdom)
• [Journal Article] Microarray analysis of macrophage response to infection with Streptococcus oralis reveals the immunosuppressive effect of hydrogen peroxide (2017)
  • Author(s): H. Matsushima, Y. Kumagai, A. Vandenbon, H. Kataoka, M. Kadena, H. Fukamachi, T. Arimoto, H. Morisaki, N. Fujiwara, N. Okahashi, and H. Kuwata
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 485(2) Issue: 2 Pages: 461-467
  • DOI: 10.1016/j.bbrc.2017.02.048
  • Peer Reviewed / Open Access
• [Journal Article] Mycobacterium stephanolepidis sp. nov., a rapid-growing species related to Mycobacterium chelonae, isolated from marine teleost fish, Stephanolepis cirrhifer (2017)
  • Author(s): H. Fukano, S.Wada, O. Kurata, K. Katayama, N. Fujiwara and Y. Hoshino.
  • Journal Title: Int. J. Syst. Evol. Microbiol. Volume: in press
  • Peer Reviewed
• [Journal Article] Glycopeptidolipid of Mycobacterium smegmatis J15cs affects morphology and survival in host cells (2015)
  • Author(s): N. Fujiwara, N. Ohara, M. Ogawa, S. Maeda, T. Naka, H. Taniguchi, S. Yamamoto, M. Ayata
  • Journal Title: PLoS One Volume: 10(5) Issue: 5 Pages: e0126813-e0126813
  • DOI: 10.1371/journal.pone.0126813
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] <i>Porphyromonas bronchialis</i> sp. nov. Isolated from Intraoperative Bronchial Fluids of a Patient with Non-Small Cell Lung Cancer (2015)
  • Author(s): T. Sato, J. Tomida, T. Naka, N. Fujiwara, A. Hasegawa, Y. Hoshikawa, J. Matsuyama, N. Ishida, T. Kondo, K. Tanaka, N. Takahashi, Y. Kawamura
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 237 Issue: 1 Pages: 31-37
  • DOI: 10.1620/tjem.237.31
  • NAID: 130005094770
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Porphyromonas pogonae sp. nov., an anaerobic but low concentration oxygen adapted coccobacillus isolated from lizards (Pogona vitticeps) or human clinical specimens, and emended description of the genus Porphyromonas Shah and Collins 1988 (2015)
  • Author(s): Y. Kawamura, S. Kuwabara, S.A. Kania, H. Kato, M. Hamagishi, N. Fujiwara, T. Sato, J. Tomida, K. Tanaka, D.A. Bemis
  • Journal Title: Syst. Appl. Microbiol. Volume: 38 Issue: 2 Pages: 104-109
  • DOI: 10.1016/j.syapm.2014.11.004
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of Mycolic Acids in Total Fatty Acid Methyl Ester Fractions from <i>Mycobacterium</i> Species by High Resolution MALDI-TOFMS (2015)
  • Author(s): Teramoto K, Suga M, Sato T, Wada T, Yamamoto A, Fujiwara N
  • Journal Title: Mass Spectrometry Volume: 4 Issue: 1 Pages: A0035-A0035
  • DOI: 10.5702/massspectrometry.A0035
  • NAID: 130005095680
  • ISSN: 2186-5116, 2187-137X
  • Peer Reviewed / Open Access
• [Journal Article] Glycerol monomycolate is a novel ligand for the human, but not mouse macrophage inducible C-type lectin, Mincle. (2014)
  • Author(s): Hattori Y, Morita, D, Fujiwara N, Mori D, Nakamura T, Harashima H, Yamasaki S, Sugita M.
  • Journal Title: The Journal of Biological Chemistry Volume: 289(22) Issue: 22 Pages: 15405-12
  • DOI: 10.1074/jbc.m114.566489
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance (2013)
  • Author(s): Fujiwara, N.
  • Journal Title: Biochim. Biophys. Acta. Volume: Mar 29 Issue: 6 Pages: 1177-84
  • DOI: 10.1016/j.bbalip.2013.03.008
  • Peer Reviewed
• [Journal Article] BCG亜株の脂質生化学的特徴 (2013)
  • Author(s): 藤原永年
  • Journal Title: 医学のあゆみ Volume: 247(7) Pages: 627-628
• [Journal Article] 非結核性抗酸菌由来糖ペプチド脂質抗原の構造、生合成経路、宿主応答機序 (2013)
  • Author(s): 藤原永年
  • Journal Title: The Lung Perspectives Volume: 22(1) Pages: 65-72
• [Presentation] Mycobacterium shigaenseの謎 (2017)
  • Author(s): 星野仁彦、吉田光範、深野華子、和田新平、藤原永年、鹿住祐子、御手洗聡
  • Organizer: 第92回日本結核病学会総会
  • Place of Presentation: 東京（東京国際フォーラム）
  • Year and Date: 2017-03-23
• [Presentation] 非結核性抗酸菌臨床分離株から分離された新規糖ペプチド脂質抗原 (2017)
  • Author(s): 藤原永年、綾田稔、中崇、桑田啓貴、前田伸司
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台（仙台国際センター展示棟）
  • Year and Date: 2017-03-19
• [Presentation] The characterization of a novel serotype-specific glycopeptidolipid from clinical nontuberculous mycobacteria (2016)
  • Author(s): N. Fujiwara, M. Ayata, T. Naka, H. Kuwata, and S. Maeda
  • Organizer: The 16th Asia-Pacific Congress of Clinical Microbiology and Infection
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-11-30
  • Int'l Joint Research
• [Presentation] Mycobcterium avium の酸性環境下での適応能に関する研究 (2016)
  • Author(s): 伊藤佐生智、堀田康弘、大原直也、小川賢二、八木哲也、前田伸司、藤原永年、山崎利雄、西森 敬、瀧井猛将
  • Organizer: 第91回日本結核病学会総会
  • Place of Presentation: 金沢（石川県立音楽堂、ホテル日航金沢）
  • Year and Date: 2016-05-27
• [Presentation] Mycobacterium smegmatis J15cs株の糖ペプチド脂質欠損による形態変化と宿主内生存 (2016)
  • Author(s): 藤原永年、大原直也、小川みどり、前田伸司、中崇、谷口初美、山本三郎、綾田稔
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-23
• [Presentation] Mycobacterium avium の酸性環境下で誘導されるアルギニンデイミナーゼの解析 (2016)
  • Author(s): 山本龍二、伊藤佐生智、堀田康弘、大原直也、小川賢二、八木哲也、前田伸司、藤原永年、山崎利雄、西森敬、後藤義孝、肥田重明、小野嵜菊夫、瀧井猛将
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-23
• [Presentation] The deletion of glycopeptidolipid in Mycobacterium smegmatis J15cs strain affects morphology and survival in host cells (2015)
  • Author(s): N. Fujiwara, M. Ayata, N. Ohara, M. Ogawa, T. Naka, H. Taniguchi, S. Yamamoto, and S. Maeda
  • Organizer: 40th FEBS Congress
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2015-07-03
  • Int'l Joint Research
• [Presentation] Production and characterization of antibodies to Mycobacterial lipid antigens in rabbit (2015)
  • Author(s): M. Shibata, T. Naka, S. Maeda, N. Fujiwara
  • Organizer: 40th FEBS Congress
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2015-07-03
  • Int'l Joint Research
• [Presentation] Genetic analysis of the glycopeptidolipids (GPLs) synthetic pathway in Mycobacterium intracellulare (2015)
  • Author(s): S. Maeda, N. Nakata, H. Yamada, N. Fujiwara
  • Organizer: 40th FEBS Congress
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2015-07-03
  • Int'l Joint Research
• [Presentation] 結核菌由来脂質抗原の家兎免疫による抗脂質IgG抗体の産生とその性質 (2015)
  • Author(s): 柴田満、前田伸司、藤原永年
  • Organizer: 第90回日本結核病学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2015-03-27 – 2015-03-28
• [Presentation] 発育にビタミンＫを要求する新しいPorphyromonas属菌種の分類学的検討 (2015)
  • Author(s): 河村好章、佐藤拓一、冨田純子、森田雄二、中崇、藤原永年、田中香里
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Identification of bacterial sphingophospholipids and their activation of murine macrophages via Toll-like receptor 4 (2014)
  • Author(s): N Fujiwara, T. Naka, H. Kuwata, S. Maeda
  • Organizer: FEBS EMBO 2014
  • Place of Presentation: Paris, France
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] Isolation of mycobacterial mutants that disrupted the phospholipid synthetase gene, and their properties (2014)
  • Author(s): S. Maeda, N. Nakata, T. Naka, M. Kai, N. Fujiwara
  • Organizer: FEBS EMBO 2014
  • Place of Presentation: Paris, France
  • Year and Date: 2014-08-30 – 2014-09-01
• [Presentation] Characterization of Bacterial Fatty Acids by MALDI spiral-TOFMS Combined with Kendrick Mass Defect Plot Analysis (2014)
  • Author(s): K. Teramoto, T. Sato, N. Fujiwara, T. Tamura, M. Hamada, Ken-ichiro Suzuki
  • Organizer: 20th International Mass Spectrometry Conference
  • Place of Presentation: Genova, Switzerland
  • Year and Date: 2014-08-24 – 2014-08-29
• [Presentation] Rapid identification of Mycobacterium using mycolic acids by MALDI spiral-TOFMS with ultra high mass-resolving power (2014)
  • Author(s): K. Teramoto, N. Fujiwara
  • Organizer: International Unions of Microbiological Societies Congress 2014
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] Porphyromonas pogonae sp. nov.: A Strong Beta-Hemolytic, Low Concentration Oxygen Tolerant Species from Lizards and Human Clinical Specimens (2014)
  • Author(s): Y. Kawamura, S. Kuwabara, S. A. Kania, H. Kato, M. Hamagishi, S. Hayakawa, N. Fujiwara, T. Naka, T. Sato, J. Tomida, K. Tanaka, T. Yoshida, Y. Morita, D. A. Bemis
  • Organizer: 114th General Meeting, The American Society for Microbiology
  • Place of Presentation: Boston, USA
  • Year and Date: 2014-05-17
• [Presentation] 超高分解能MALDI Spiral-TOFMSによるミコール酸の簡易迅速分析法の開発 (2014)
  • Author(s): 藤原永年、和田崇之、前田伸司
  • Organizer: 第89回日本結核病学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2014-05-09 – 2014-05-10
• [Presentation] BCG Tokyo172-1に存在するサブポピュレーションの比率変化に関する検討 (2014)
  • Author(s): 大原直也、趙娜、和田崇之、藤原永年、前田伸司、山本三郎、瀧井猛将，前山順一
  • Organizer: 第89回日本結核病学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2014-05-09 – 2014-05-10
• [Presentation] Mycobacterium aviumの酸性環境下におけるアルギニンデイミナーゼ誘導機構の解析 (2014)
  • Author(s): 小川翔大、山本龍二、堀田康弘、花村菜月、筑比地慧、宮田江里香、高見篤郎、徳田美季、富田陽香、小川賢二、八木哲也、大原直也、藤原永年、前田伸司、山崎利雄、西森敬、後藤義孝、伊藤佐生智、小野嵜菊夫、瀧井猛将
  • Organizer: 第84回実験結核研究会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2014-05-08
• [Presentation] 細胞内感染したMAC菌における糖ペプチド脂質抗原の分子種組成変化 (2014)
  • Author(s): 中崇、前田伸司、柴田満、水野淨子、藤原永年
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京（タワーホール船堀）
• [Presentation] 超高分解能MALDI spiral-TOFMSによる結核菌ミコール酸の迅速分析 (2014)
  • Author(s): 寺本華奈江、藤原永年
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京（タワーホール船堀）
• [Presentation] Bacterial sphingophospholipids activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance (2013)
  • Author(s): N. Fujiwara, T. Naka, H. Kuwata, S. Maeda
  • Organizer: FEMS 2013-The 5th Congress of European Microbiologists
  • Place of Presentation: Reipzig, Germany
• [Presentation] Application of MALDI Spiral-TOF MS with High Mass Resolving Power to Assign Mycolic Acid Subclasses in Mycobacterium tuberculosis (2013)
  • Author(s): K. Teramoto, T. Sato, T. Wada, A. Yamamoto, N. Fujiwara
  • Organizer: FEMS 2013-The 5th Congress of European Microbiologists
  • Place of Presentation: Reipzig, Germany
• [Presentation] Novel serotype-specific glycopeptidolipid from Mycobacterium intracellulare clinical isolate (2013)
  • Author(s): N. Fujiwara, T. Naka, M. Ayata, M. Shibata, H. Kuwata, H. Ogura, S. Maeda
  • Organizer: The 5th EMBO meeting
  • Place of Presentation: Amsterdam, The Netherlands
• [Presentation] enotyping of Mycobacterium tuberculosis (MTB), especially Beijing genotype MTB, in Japan by using the variable-number of tandem repeats (VNTR) and a next generation sequencer (NGS) (2013)
  • Author(s): S. Maeda, T. Wada , T. Naka , M. Shibata , N. Fujiwara
  • Organizer: The 5th EMBO meeting
  • Place of Presentation: Amsterdam, The Netherlands
• [Presentation] Production of anti-lipid IgG antibodies in rabbit immunized with mycobacterial lipid antigens (2013)
  • Author(s): M. Shibata, T. Naka, S. Maeda, and N. Fujiwara
  • Organizer: The 5th EMBO meeting
  • Place of Presentation: Amsterdam, The Netherlands