Analysis of control method of bacterial pneumonia utilizing functional glycolipids and researching its molecular mechanism

• Project/Area Number: 15H05017
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Kyoto Pharmaceutical University (2016-2017); Niigata University (2015)
• Principal Investigator: ODA MASATAKA 京都薬科大学, 薬学部, 教授 (00412403)
• Co-Investigator(Kenkyū-buntansha): 土門 久哲 新潟大学, 医歯学系, 助教 (00594350) ; 寺尾 豊 新潟大学, 医歯学系, 教授 (50397717)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: 機能性糖脂質 / 肺炎 / 細胞外捕獲網 / 肺炎球菌 / 緑膿菌 / ビザンチン / 水溶性糖脂質 / マクロファージ細胞外捕獲網 / PRSP / MDRP / MRSA / 水溶性ビザンチン / C型レクチン / Toll様受容体 / 細菌性肺炎 / NETs / 肺炎モデルマウス / 好中球

Outline of Final Research Achievements

In this research project, experiments were carried out to analyze the effect of newly developed water-soluble glycolipid (WSG) on bacterial pneumonia and its mechanism. As a result, the following three things were revealed.1) WSG induced the extracellular release of a net structure containing nucleic acid as a main component in macrophages or neutrophils. Especially in macrophages, it was found that mitochondria-derived nucleic acid was released with little cell death and trapped Streptococcus pneumoniae and Pseudomonas aeruginosa.2) Analysis using inhibitors and knockdown cells suggested that the WSG act on the mincle receptor other than TLR4 receptor.
3) Pneumonia and mortality caused by S. pneumoniae were suppressed by nasal administration of WSG.

Research Products

• [Journal Article] Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-like Receptors and Cytokines in Pneumococcal Pneumonia (2018)
  • Author(s): Domon Hisanori、Nagai Kosuke、Maekawa Tomoki、Oda Masataka、Yonezawa Daisuke、Takeda Wataru、Hiyoshi Takumi、Tamura Hikaru、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Front Immunol Volume: 印刷中 Pages: 732-732
  • DOI: 10.3389/fimmu.2018.00732
  • Peer Reviewed / Open Access
• [Journal Article] Sulfated vizantin induces the formation of macrophage extracellular traps (2018)
  • Author(s): Oda Masataka、Kurosawa Mie、Yamamoto Hirofumi、Domon Hisanori、Kimura Tatsuya、Isono Toshihito、Maekawa Tomoki、Hayashi Naoki、Yamada Noriteru、Furue Yui、Kai Daichi、Terao Yutaka
  • Journal Title: Microbiol Immunol Volume: 印刷中 Issue: 5 Pages: 0-0
  • DOI: 10.1111/1348-0421.12589
  • NAID: 40021560445
  • Peer Reviewed / Open Access
• [Journal Article] Antimicrobial activity of the constituents of Dalbergia tonkinensis Prain and structural-bioactive highlights. (2018)
  • Author(s): Nihin The Son, Masataka Oda, Naoki Hayashi, Daiki Yamaguchi, Yu Kawagishi, Fumi Takahashi, Kenichi Harada, Nguyen Manh Cuong, and Yoshiyasu Fukuyama
  • Journal Title: Nat. Prod. Commun. Volume: 13 Pages: 157-161
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pneumococcal DNA-binding proteins released through autolysis induce the production of proinflammatory cytokines via toll-like receptor 4 (2018)
  • Author(s): Nagai Kosuke、Domon Hisanori、Maekawa Tomoki、Oda Masataka、Hiyoshi Takumi、Tamura Hikaru、Yonezawa Daisuke、Arai Yoshiaki、Yokoji Mai、Tabeta Koichi、Habuka Rie、Saitoh Akihiko、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Cell Immunol Volume: 325 Pages: 14-22
  • DOI: 10.1016/j.cellimm.2018.01.006
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus pyogenes CAMP factor promotes bacterial adhesion and invasion in pharyngeal epithelial cells without serum via PI3K/Akt signaling pathway (2018)
  • Author(s): Kurosawa Mie、Oda Masataka、Domon Hisanori、Isono Toshihito、Nakamura Yuki、Saitoh Issei、Hayasaki Haruaki、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Microbes Infect Volume: 20 Issue: 1 Pages: 9-18
  • DOI: 10.1016/j.micinf.2017.09.007
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus pyogenes Phospholipase A2 Induces the Expression of Adhesion Molecules on Human Umbilical Vein Endothelial Cells and Aorta of Mice (2017)
  • Author(s): Oda Masataka、Domon Hisanori、Kurosawa Mie、Isono Toshihito、Maekawa Tomoki、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
  • Journal Title: Front Cell Infect Microbiol Volume: 7 Pages: 300-300
  • DOI: 10.3389/fcimb.2017.00300
  • Peer Reviewed / Open Access
• [Journal Article] Isolation and characterization of lymphoid enhancer factor-1-positive deciduous dental pulp stem-like cells after transfection with a piggyBac vector containing LEF1 promoter-driven selection markers. (2017)
  • Author(s): Murakami T, Saitoh I, Sato M, Inada E, Soda M, Oda M, Domon H, Iwase Y, Sawami T, Matsueda K, Terao Y, Ohshima H, Noguchi H, Hayasaki H
  • Journal Title: Archives of Oral Biology Volume: 81 Pages: 110-120
  • DOI: 10.1016/j.archoralbio.2017.04.033
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential Expression and Roles of Secreted Frizzled-Related Protein and the Wingless Homolog Wnt5a in Periodontitis. (2017)
  • Author(s): Maekawa T, Kulwattanaporn P, Hosur K, Domon H, Oda M, Terao Y, Maeda T, Hajishengallis G.
  • Journal Title: J Dent Res Volume: 96(5) Issue: 5 Pages: 571-577
  • DOI: 10.1177/0022034516687248
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Poor survival of Methicillin-resistant Staphylococcus aureus on inanimate objects in the public spaces. (2016)
  • Author(s): Hisanori Domon, Yoshio Uehara, Masataka Oda, Hiromi Seo, Noriko Kubota, and Yutaka Terao
  • Journal Title: Microbiologyopen Volume: 5 Pages: 39-46
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells. (2016)
  • Author(s): Kurosawa M, Oda M, Domon H, Saitoh I, Hayasaki H, Terao Y.
  • Journal Title: Microbes Infect. Volume: 18 Issue: 2 Pages: 118-127
  • DOI: 10.1016/j.micinf.2015.10.003
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Anti-biofilm and bactericidal effects of magnolia bark-derived magnolol and honokiol on Streptococcus mutans, (2016)
  • Author(s): Sakaue, Y.; Domon, H.; Oda, M.; Takenaka, S.; Kubo, M.; Fukuyama, Y.; Okiji, T.; Terao, Y.
  • Journal Title: Microbiol. Immunol. Volume: 60 Issue: 1 Pages: 10-16
  • DOI: 10.1111/1348-0421.12343
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chemical Hybridization of Vizantin and Lipid A to Generate a Novel LPS Antagonist (2016)
  • Author(s): Yamamoto H, Oda M, Kanno M, Tamashiro S, Tamura I, Yoneda T, Yamasaki N, Domon H, Nakano M, Takahashi H, Terao Y, Kasai Y, Imagawa H.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 3 Pages: 246-257
  • DOI: 10.1248/cpb.c15-00828
  • NAID: 130005131585
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oligomer formation of Clostridium perfringens epsilon-toxin is induced by activation of neutral sphingomyelinase. (2016)
  • Author(s): Takagishi T, Oda M, Takehara M, Kobayashi K, Nagahama M.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1858 Issue: 11 Pages: 2681-2688
  • DOI: 10.1016/j.bbamem.2016.07.009
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Vizantin inhibits bacterial adhesion without affecting bacterial growth and causes Streptococcus mutans biofilm to detach by altering its internal architecture (2016)
  • Author(s): Takenaka S, Oda Masataka, Domon H, Suzuki Y, Ohshima H, Yamamoto H, Tarao Y, Noiri Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 480 Issue: 2 Pages: 173-179
  • DOI: 10.1016/j.bbrc.2016.10.021
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Streptococcus pneumoniae disrupts pulmonary immune defence via elastase release following pneumolysin-dependent neutrophil lysis. (2016)
  • Author(s): Domon H, Oda M, Maekawa T, Nagai K, Takeda W, Terao Y.
  • Journal Title: Sci Rep Volume: オンラインジャーナル Issue: 1 Pages: 38013-38013
  • DOI: 10.1038/srep38013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clostridium perfringens alpha-toxin induces GM1a clustering and TrkA phosphorylation in the host cell membrane. (2015)
  • Author(s): Takagishi, T., Oda, M., Kabura, M., Kurosawa, M., Tominaga, K., Urano, S., Ueda, Y.,Kobayashi, K., Kobayashi, T., Sakurai, J., Terao, Y., and Nagahama, M.
  • Journal Title: PLoS one Volume: 10 Issue: 4 Pages: e0120497-e0120497
  • DOI: 10.1371/journal.pone.0120497
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tetranorsesquiterpenoids and Santalane-Type Sesquiterpenoids from Illicium lanceolatum and Their Antimicrobial Activity against the Oral Pathogen Porphyromonas gingivalis. (2015)
  • Author(s): Kubo, M.; Nishikawa, Y.; Harada, K.; Oda, M.; Huang, J.-M.; Domon, H.; Terao, Y.; Fukuyama, Y.
  • Journal Title: J. Nat. Prod. Volume: 78 Issue: 6 Pages: 1466-1469
  • DOI: 10.1021/acs.jnatprod.5b00237
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Membrane-Binding Mechanism of Clostridium perfringens Alpha-Toxin. (2015)
  • Author(s): Oda M, Terao Y, Sakurai J, Nagahama M.
  • Journal Title: Toxins Volume: 7 Issue: 12 Pages: 5268-5275
  • DOI: 10.3390/toxins7124880
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of the replication region in pBCNF5603, a bacteriocin-encoding plasmid, in the enterotoxigenic Clostridium perfringens strain F5603. (2015)
  • Author(s): Miyamoto K, Seike S, Takagishi T, Okui K, Oda M, Takehara M, Nagahama M
  • Journal Title: BMC Microbiol. Volume: 15 Issue: 1 Pages: 118-118
  • DOI: 10.1186/s12866-015-0443-3
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Total Synthesis of Palau’amine (2015)
  • Author(s): K. Namba, K. Takeuchi, Y. Kaihara, M. Oda, A. Nakayama, A. Nakayama, M. Yoshida, and K. Tanino
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 8731-8731
  • DOI: 10.1038/ncomms9731
  • NAID: 120006999407
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] AMR対策を志向した免疫賦活剤の開発研究 (2018)
  • Author(s): 小田真隆
  • Organizer: 第33回 日本環境感染学会総会・学術集会
  • Invited
• [Presentation] 腸管上皮細胞が緑膿菌によるムチン層透過を亢進するメカニズムの解析 (2017)
  • Author(s): 林直樹，後藤直正、小田真隆
  • Organizer: 平成29年度 近畿腸管微生物研究会総会・研究発表会
• [Presentation] 多剤耐性緑膿菌感染マウスに対する機能性糖脂質の効果 (2017)
  • Author(s): 西澤渚，林直樹，小田真隆
  • Organizer: 第29回 微生物シンポジウム
• [Presentation] 緑膿菌によるムチン層透過に与えるサイトカインの影響 (2017)
  • Author(s): 横谷篤，林直樹，後藤直正，小田真隆
  • Organizer: 第29回 微生物シンポジウム
• [Presentation] 能性糖脂質によるマクロファージ細胞外捕獲網の発現誘導 (2017)
  • Author(s): 小田真隆
  • Organizer: 第11回 次世代を担う若手医療薬科学シンポジウム
• [Presentation] 肺炎球菌性肺炎の重症化メカニズムの分子解析 (2016)
  • Author(s): 土門久哲，小田真隆，川端重忠，寺尾豊
  • Organizer: 第65回日本感染症学会東日本地方会学術集会・第63回日本化学療法学会東日本支部総会・合同学会
  • Place of Presentation: 朱鷺メッセ（新潟県、新潟市）
  • Year and Date: 2016-10-26
• [Presentation] A群レンサ球菌のPI3K/Akt活性化因子を介した咽頭上皮細胞株への付着・侵入メカニズムの解析 (2016)
  • Author(s): 黒澤 美絵，小田 真隆，土門 久哲，齊藤一誠，早﨑治明，寺尾豊
  • Organizer: 第58回歯科基礎医学会
  • Place of Presentation: 札幌コンベンションセンター（北海道，札幌）
  • Year and Date: 2016-08-24
• [Presentation] Streptococcus mutansバイオフィルムに対する厚朴由来抽出物の殺菌効果 (2016)
  • Author(s): 坂上雄樹，土門久哲，小田真隆，竹中彰治，大墨竜也，寺尾 豊，野杁由一郎
  • Organizer: 第30回日本バイオフィルム学会学術集会
  • Place of Presentation: 第一三共本社ビル（東京都，中央区）
  • Year and Date: 2016-07-02
• [Presentation] 肺炎球菌の自己融解に起点を発する肺障害のカスケード機構 (2016)
  • Author(s): 土門久哲，小田真隆，寺尾豊
  • Organizer: 第55回新潟化学療法研究会
  • Place of Presentation: ANAクラウンホテル（新潟県，新潟市）
  • Year and Date: 2016-07-02
• [Presentation] 多機能性糖脂質によるマクロファージ細胞外捕獲網形成機構の解明 (2016)
  • Author(s): 小田真隆、黒澤美絵、土門久哲、寺尾豊
  • 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 （大阪府、大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 肺炎球菌による肺組織傷害誘導メカニズムの解析 (2016)
  • Author(s): 土門久哲，坂上雄樹，小田真隆，山口雅也，川端重忠，寺尾豊
  • 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 （大阪府、大阪市）
  • Year and Date: 2016-03-23
• [Presentation] Streptococcus pyogenesの咽頭上皮細胞株への付着・侵入におけるCAMP factorの役割 (2016)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，寺尾豊
  • 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 （大阪府、大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 多機能性糖脂質によるマクロファージMETs形成メカニズムの解析 (2015)
  • Author(s): 小田真隆、黒澤美絵、土門久哲、寺尾豊
  • Organizer: 第57回歯科基礎医学会学術大会・総会
  • Place of Presentation: 朱鷺メッセ (新潟県・新潟市)
  • Year and Date: 2015-09-11
• [Presentation] 肺炎球菌による宿主細胞の細胞死誘導能の解析 (2015)
  • Author(s): 土門久哲，坂上雄樹，小田真隆，山口雅也，川端重忠，寺尾豊
  • Organizer: 第57回歯科基礎医学会学術大会・総会
  • Place of Presentation: 朱鷺メッセ (新潟県・新潟市)
  • Year and Date: 2015-09-11
• [Presentation] Streptococcus pyogenes CAMP factorのRAW264.7細胞に対する空胞形成メカニズムの検討 (2015)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，斎藤 一誠，早崎治明，寺尾豊
  • Organizer: 第57回歯科基礎医学会学術大会・総会
  • Place of Presentation: 朱鷺メッセ (新潟県・新潟市)
  • Year and Date: 2015-09-11
• [Book] Microbial Biofilms- Importance and applications (Chapter 18) (2016)
  • Author(s): Shoji, Takenaka, Masataka Oda, Hisanori Domon, Wakamatsu, R., Ohsumi, T., Terao, Y., and Noiri, Y.
  • Total Pages: 16
  • Publisher: InTech
• [Book] 口腔微生物学・免疫学 第４版 (2015)
  • Author(s): 小田真隆
  • Total Pages: 21
  • Publisher: 医歯薬出版
• [Remarks] 京都薬科大学 微生物・感染制御学分野ホームページ
  • URL: http://labo.kyoto-phu.ac.jp/bisei/
• [Remarks] 京都薬科大学 微生物・感染制御学分野
  • URL: http://labo.kyoto-phu.ac.jp/bisei/
• [Remarks] 新潟大学 大学院医歯学総合研究科 微生物感染症学分野
  • URL: http://www.dent.niigata-u.ac.jp/microbio/microbio.html
• [Patent(Industrial Property Rights)] リン酸基を有するトレハロース化合物及びその用途 (2017)
  • Inventor(s): 小田真隆，山本博文
  • Industrial Property Rights Holder: 大塚化学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
• [Patent(Industrial Property Rights)] リン酸基を有するトレハロース化合物及びその用途 (2016)
  • Inventor(s): 小田真隆
  • Industrial Property Rights Holder: 大塚化学株式会社
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-03-02