細菌感染症の転帰を決める細胞ロジスティクス機構の分子基盤解析

• Project Area: Intracellular logistics: interdisciplinary approaches to pathophysiology of membrane traffic
• Project/Area Number: 23113715
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: 天野 敦雄 大阪大学, 歯学研究科(研究院), 教授 (50193024)
• Project Period (FY): 2011-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: メンブレントラッフィク / オートファジー / 歯周病菌 / 感染 / 歯学 / 細菌感染 / 細胞・組織 / メンブレントラフィック / SNARE

Outline of Annual Research Achievements

歯周病菌は歯肉上皮細胞や歯肉繊維芽細胞に侵入し、感染の進行と慢性化を図る。一方、宿主細胞はエンドサイトーシス経路などのメンブレントラフィック機構を用いて侵入細菌を分解する。この「細菌 vs メンブレントラフィック」の戦いの転機が歯周病の発症において大きな影響を与えている。
メンブレントラフィック機構のひとつであるオートファジー（自食作用）とは、細胞の中を掃除することで病気が起こるのを防ぐ仕組である。細胞の中に壊れたミトコンドリアや古いタンパク質などが溜まったり病原体が侵入したりすると、細胞の健康が損なわれ、その結果アルツハイマー病、発がん、心不全、糖尿病、感染症、炎症など多岐にわたる病気が起こる。それを防ぐために細胞はオートファジーという仕組みを持っている。オートファジーを担うオートファゴソームは、膜で包まれた球形のオルガネラであり、必要に応じて細胞の中に現れ、細胞にとって有害な上述のものを取り込んで分解する働きを持つ清掃マシーンのような存在である。どこからともなく現れ役目を終えると消えるため、どこで造られているのかがこれまで40年近く論争の的になっていた。
最も強力な歯周病菌でもあるP. gingivalis は細胞質内へと侵入しオートファジーにより捕獲され分解・殺菌される。我々はオートファゴソームの形成起源について検討を加えた。その結果、オートファゴソームが別のオルガネラであるミトコンドリアと小胞体が接触する場所で造られていることを見出した。さらに、歯周病菌は細胞のリサイクリング経路をハイジャックすることにより細胞外に脱出し、隣接細胞に再侵入することにより組織内での感染を拡大させていることも明かとした。

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Porphyromonas gingivalis fimbriae (2013)
  • Author(s): Enersen M
  • Journal Title: Journal of Oral Microbiology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Characterization of periodontal biofilm in Down syndrome patients: a comparative study (2013)
  • Author(s): Martinez-Martinez RE
  • Journal Title: Journal of Medical Microbiology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Genotype analysis of Porphyromonas gingivalis fimA in Korean adults using new primers (2013)
  • Author(s): Moon JH
  • Journal Title: Journal of Medical Microbiology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] The serine phosphatase SerB of Porphyromonas gingivalis suppresses IL-8 production by dephosphorylation of NF-κB RelA/p65 (2013)
  • Author(s): Takeuchi H, Hirano T, Whitmore SE, Morisaki I, Amano A, Lamont RJ
  • Journal Title: PLoS Pathogens Volume: 9(4) Issue: 4 Pages: 1-13
  • DOI: 10.1371/journal.ppat.1003326
  • Peer Reviewed
• [Journal Article] Autophagosomes form at ER.mitochondria contact sites (2013)
  • Author(s): Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T
  • Journal Title: Nature Volume: 495 Issue: 7441 Pages: 389-93
  • DOI: 10.1038/nature11910
  • Peer Reviewed
• [Journal Article] Identification and characterization of Porphyromonas gingivalis client proteins that bind to Streptococcus oralis Glyceraldehyde-3-Phosphate Dehydrogenase (2013)
  • Author(s): Maeda K, Nagata H, Kuboniwa M, Ojima M, Osaki T, Minamino N, Amano A
  • Journal Title: Infection and Immunity Volume: 81(3) Issue: 3 Pages: 753-763
  • DOI: 10.1128/iai.00875-12
  • Peer Reviewed
• [Journal Article] Distribution and molecular characterization of Porphyromonas gulae carrying a new fimA genotype (2012)
  • Author(s): Yamasaki Y, Nomura R, Nakano K, Inaba H, Kuboniwa M, Hirai N, Shirai M, Kato Y, Murakami M, Naka S, Iwai S, Matsumoto-Nakano M, Ooshima T, Amano A, Asai F
  • Journal Title: Veterinary Microbiology Volume: 161(1) Issue: 1-2 Pages: 196-205
  • DOI: 10.1016/j.vetmic.2012.07.026
  • Peer Reviewed
• [Journal Article] Identification of signaling pathways mediating cell cycle arrest and apoptosis induced by Porphyromonas gingivalis in human trophoblasts (2012)
  • Author(s): Inaba H, Kuboniwa M, Sugita H, Lamont RJ, Amano A
  • Journal Title: Infection and Immunity Volume: 80(8) Issue: 8 Pages: 2847-2857
  • DOI: 10.1128/iai.00258-12
  • Peer Reviewed
• [Journal Article] Insights into the virulence of oral biofilms : discoveries from proteomics (2012)
  • Author(s): Kuboniwa M, Tribble GD, Hendrickson EL, Amano A, Lamont RJ, Hackett M
  • Journal Title: Expert Review of Proteomics Volume: 9(3) Issue: 3 Pages: 311-323
  • DOI: 10.1586/epr.12.16
  • Peer Reviewed
• [Journal Article] Negative regulation of Odd-skipped related 2 by TGF-achieves the induction of cellular migration and the arrest of cell cycle (2012)
  • Author(s): Kawai S, Amano A
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 421(4) Issue: 4 Pages: 696-700
  • DOI: 10.1016/j.bbrc.2012.04.064
  • Peer Reviewed
• [Journal Article] BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex (2012)
  • Author(s): Kawai S, Amano A
  • Journal Title: Journal of Cell Biology Volume: 197(2) Issue: 2 Pages: 201-208
  • DOI: 10.1083/jcb.201110008
  • Peer Reviewed
• [Journal Article] Cardiovascular diseases and periodontal diseases (2012)
  • Author(s): Amano A
  • Journal Title: Clinical Calcium Volume: 22 Pages: 43-48
• [Journal Article] Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease (2012)
  • Author(s): Yoneda M, Naka S, Nakano K, Wada K, Endo H, Mawatari H, Imajo K, Nomura R, Hokamura K, Ono M, Murata S, Tohnai I, Sumida Y, Shima T, Kuboniwa M, Umemura K, Kamisaki Y, Amano A, Okanoue T, Ooshima T, Nakajima A.
  • Journal Title: BMC Gastroenterol Volume: 12 Issue: 1 Pages: 12-16
  • DOI: 10.1186/1471-230x-12-16
  • Peer Reviewed
• [Journal Article] Development and evaluation of new primers for PCR-based identification of type II fimA of Porphyromonas gingivalis (2012)
  • Author(s): Moon JH, et al
  • Journal Title: FEMS Immunology & Medical Microbiology Volume: Nov 3(In press) Issue: 3 Pages: 425-428
  • DOI: 10.1111/j.1574-695x.2011.00889.x
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky DJ
  • Journal Title: Autophagy Volume: 8 Pages: 445-544
  • Peer Reviewed
• [Journal Article] SNARE mediates autophagosome-lysosome fusion (2012)
  • Author(s): Furuta N
  • Journal Title: Journal of Oral Bioscience Volume: 54 Pages: 83-85
  • Peer Reviewed
• [Journal Article] Cell entry and exit by periodontal pathogen Porphyromonas gingivalis (2012)
  • Author(s): Amano A
  • Journal Title: Journal of Oral Bioscience Volume: 54 Pages: 54-57
  • Peer Reviewed
• [Journal Article] Transition metal ions induce carnosinase activity in PepD-homologous protein from Porphyromonas gingivalis (2012)
  • Author(s): Aoki A, et al
  • Journal Title: Microbial Pathogenesis Volume: 52 Pages: 17-24
  • Peer Reviewed
• [Journal Article] Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease (2012)
  • Author(s): Yoneda M, et al
  • Journal Title: BMC Gastroenterology Volume: 12 Pages: 16-16
  • Peer Reviewed
• [Journal Article] BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex (2012)
  • Author(s): Kawai S, et al
  • Journal Title: Journal of Cell Biology Volume: 192 Pages: 201-208
  • Peer Reviewed
• [Journal Article] Insights into the pathogenesis of dental plaque : discoveries from proteomics (2012)
  • Author(s): Kuboniwa M, et al
  • Journal Title: Expert Review Volume: (in press)
  • Peer Reviewed
• [Journal Article] 循環器疾患と歯周病 (2012)
  • Author(s): 天野敦雄, 他
  • Journal Title: CLINICAL CALCIUM Volume: 22 Pages: 43-48
• [Journal Article] 病因論から再考する歯周治療 (2012)
  • Author(s): 天野敦雄
  • Journal Title: 障害者歯科 Volume: 32 Pages: 1-7
  • NAID: 10030299367
• [Journal Article] Characterization of aortic aneurysms in cardiovascular disease patients harboring Porphyromonas gingivalis (2011)
  • Author(s): Nakano K, et al
  • Journal Title: Oral Diseases Volume: 17 Pages: 370-378
  • Peer Reviewed
• [Journal Article] Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis (2011)
  • Author(s): Sugita A, et al
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 3094-3103
  • Peer Reviewed
• [Journal Article] Exit of intracellular Porphyromonas gingivalis from gingival epithelial cells is mediated by endocytic recycling pathway (2011)
  • Author(s): Takeuchi H, et al
  • Journal Title: Cellular Microbiology Volume: 13 Pages: 677-691
  • Peer Reviewed
• [Journal Article] The collagen-binding protein of Streptococcus mutans is involved in hemorrhagic stroke (2011)
  • Author(s): Nakano K, et al
  • Journal Title: Nature Communications Volume: 2 Pages: 485-485
  • Peer Reviewed
• [Journal Article] Consideration on English education at Osaka University Graduate School of Dentistry (2011)
  • Author(s): Hamazaki Y, et al
  • Journal Title: Journal of Osaka University Dental Society Volume: 56 Pages: 5-30
• [Journal Article] Proliferation of smooth muscle cells stimulated with Porphyromonas gingivalis is inhibited by apple polyphenol (2011)
  • Author(s): Inaba H, et al
  • Journal Title: Journal of Periodontology Volume: 82 Pages: 1616-1622
  • Peer Reviewed
• [Journal Article] Cell entry and exit by periodontal pathogen via recycling pathway (2011)
  • Author(s): Takeuchi H, et al
  • Journal Title: Communicative & Integrative Biology Volume: 4 Pages: 587-589
  • Peer Reviewed
• [Journal Article] Cell entry and exit by periodontal pathogen Porphyromonas gingivalis (2011)
  • Author(s): Amano A, et al
  • Journal Title: Journal of Oral Bioscience Volume: 54 Pages: 54-57
  • Peer Reviewed
• [Journal Article] 歯周病と4つの全身疾患 (2011)
  • Author(s): 天野敦雄, 他
  • Journal Title: 臨床薬理 Volume: 42 Pages: 65-66
  • NAID: 10029432651
• [Presentation] Molecular basis of periodontal destruction by periodontal bacteria (2013)
  • Author(s): Amano A
  • Organizer: 2nd meeting of IADR-Asia Pacific Region
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2013-08-21
  • Invited
• [Presentation] 口腔から挑むBioResearch：Dental Scienceのときめき (2013)
  • Author(s): 天野敦雄
  • Organizer: 第62回口腔衛生学会
  • Place of Presentation: 松本
  • Year and Date: 2013-05-16
  • Invited
• [Presentation] Strategy of periodontal bacteria for periodontal destruction (2013)
  • Author(s): Amano A
  • Organizer: Seminar at School of Dentistry University of Louisville
  • Place of Presentation: Louisville, Kentucky
  • Year and Date: 2013-03-18
  • Invited
• [Presentation] Strategy of periodontal bacteria for periodontal destruction (2013)
  • Author(s): Amano A
  • Organizer: Seminar at Penn Dental
  • Place of Presentation: Philadelphia, Pennsylvania
  • Year and Date: 2013-03-15
  • Invited
• [Presentation] The autophagosome forms at ER#8722;mitochondria contact sites (2012)
  • Author(s): Hamasaki M
  • Organizer: Annual meeting of American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-12-16
• [Presentation] Osaka university graduate school of dentistry opens the Frontier of Biodentistry (2012)
  • Author(s): Amano A
  • Organizer: The first Japan-Thailand-Korea joint symposium on translational research in oral sciences
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2012-11-16
  • Invited
• [Presentation] Strategy of P. gingivalis for periodontal destruction (2012)
  • Author(s): Amano A
  • Organizer: First international conference on Porphyromonas gingivalis and related bacterial species
  • Place of Presentation: Nagasaki
  • Year and Date: 2012-08-28
  • Invited
• [Presentation] 基礎研究が指し示す歯周病因論 (2012)
  • Author(s): 天野敦雄
  • Organizer: 第61回口腔衛生学会
  • Place of Presentation: 横須賀
  • Year and Date: 2012-05-27
  • Invited
• [Presentation] Starategy of periodontal bacteria for periodontal destruction (2012)
  • Author(s): Amano A
  • Organizer: The 2^<nd> International Joint Symposium on Oral and Dental Sciences
  • Place of Presentation: Yogjakarta (Indonesia)(招待講演)
  • Year and Date: 2012-03-02
• [Presentation] 口腔領域の遺伝子診断「病因論から予測する歯周病発症リスク」 (2011)
  • Author(s): 天野敦雄
  • Organizer: 大阪府病院診療所歯科部長会・研修会
  • Place of Presentation: ホテルモントレー大阪(大阪市)(招待講演)
  • Year and Date: 2011-12-03
• [Presentation] 病因論から再考する歯周治療 (2011)
  • Author(s): 天野敦雄
  • Organizer: 障害者歯科学会教育講座、第28回日本障害者歯科学会学術大会
  • Place of Presentation: 福岡国際会議場(福岡市)(招待講演)
  • Year and Date: 2011-11-05
• [Presentation] Outer membrane vesicles function as offensive weapons of Porphyromonas gingrvalis (2011)
  • Author(s): Amano A
  • Organizer: The Second Osaka Mahidol Chulalongkorn Joint Symposium
  • Place of Presentation: Bangkok (Thailand)(招待講演)
  • Year and Date: 2011-10-25
• [Presentation] Outer membrane vesicles function as offensive weapons of Porphyromonas gingivalis (2011)
  • Author(s): Amano A
  • Organizer: 13rd International Congress of Bacteriology and Applied Microbiology
  • Place of Presentation: 札幌コンベンションセンター(札幌市)(招待講演)
  • Year and Date: 2011-09-03
• [Presentation] Strategy of periodontal bacteria for periodontal destruction (2011)
  • Author(s): Amano A
  • Organizer: Periodontik Terkini, Universitas Gadjah Mada
  • Place of Presentation: ガジャマダ大学(Indonesia)(招待講演)
  • Year and Date: 2011-07-04
• [Presentation] 細菌感染症の転帰を決める細胞ロジスティクス機構の分子基盤解析 (2011)
  • Author(s): 天野敦雄, 他
  • Organizer: 新学術領域「細胞内ロジスティクス」班会議
  • Place of Presentation: 鳥羽シーサイドホテル(鳥羽市)
  • Year and Date: 2011-06-01
• [Book] オートファジー (2012)
  • Author(s): 天野敦雄
  • Total Pages: 230
  • Publisher: 化学同人
• [Book] ビジュアル 歯周病を科学する (2012)
  • Author(s): 天野敦雄
  • Total Pages: 348
  • Publisher: クインテッセンス出版
• [Book] 歯周病を科学する (2012)
  • Author(s): 天野敦雄, 他
  • Publisher: クインテッセンス出版
• [Book] 病原菌の今日的意味 (2011)
  • Author(s): 天野敦雄, 他
  • Publisher: 医薬ジャーナル