Study of Clostridium perfringens beta-tox in : binding to lipid-rafts and effect on signal transduction.

• Project/Area Number: 21590500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Tokushima Bunri University
• Principal Investigator: NAGAHAMA Masahiro 徳島文理大学, 薬学部, 教授 (40164462)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Keiko 徳島文理大学, 薬学部, 助教 (90170315)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ウエルシュ菌 / β毒素 / THP-1細胞 / マイクロドメイン / ネクローシス / ホスホリパーゼC

Research Abstract

Incubation of THP-l cells with C. perfringens beta-toxin showed the formation of oligomer on lipid rafts. Beta-toxin induced the activation of endogenous phospholipase C and production of IP_3.IP_3-induced Ca^<2+> uptake caused the activation of calmodulin-calcineurin signaling pathway. As beta-toxin caused PI entry and cell swelling, beta-toxin produced cytotoxic activity through necrosis.

Research Products

• [Journal Article] Syntheses of structurally-simplified and fluorescently-labeled neovibsanin derivatives and analysis of their neurite outgrowth activity in PC12 cells (2012)
  • Author(s): Imagawa H, Nagahama M, 他15名
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 22 Pages: 2089-2093
  • Peer Reviewed
• [Journal Article] Role of side-edge site of sphingomyelinase from Bacillus cereus (2012)
  • Author(s): Oda M, Nagahama M, 他3名
  • Journal Title: Biochem. Biophys. Res. Commun Volume: (in press)
  • Peer Reviewed
• [Journal Article] Role of sphingomyelinase in infectious diseases caused by Bacillus cereus. (2012)
  • Author(s): Masataka Oda
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e38054-e38054
  • DOI: 10.1371/journal.pone.0038054
  • Peer Reviewed
• [Journal Article] Clostridium perfringens iota-b induces rapid cell necrosis (2011)
  • Author(s): Nagahama M, Kobayashi K, 他6名
  • Journal Title: Infect. Immun Volume: 79 Pages: 4353-4360
  • Peer Reviewed
• [Journal Article] Cellular vacuolation induced by Clostridium perfringens epsilon-toxin (2011)
  • Author(s): Nagahama M, Kobayashi K, 他8名
  • Journal Title: FEBS J Volume: 278 Pages: 3395-3407
  • Peer Reviewed
• [Journal Article] Induction of neurite-outgrowth in PC12 cells by alpha-toxin from Clostridiperfringens (2011)
  • Author(s): Oda M, Nagahama M, 他3名
  • Journal Title: Biochem. Biophys. Res. Commun. um Volume: 411 Pages: 241-246
  • Peer Reviewed
• [Journal Article] Identification of novel Clostridium perfringens Type E strains that carry an iota toxin plasmid with a functional enterotoxin gene (2011)
  • Author(s): Miyamoto K, Nagahama M, 他5名
  • Journal Title: PLoS one Volume: 6 Pages: 20376-20376
  • Peer Reviewed
• [Journal Article] Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily proteins (2011)
  • Author(s): Nagahama M, Kobayashi K, 他5名
  • Journal Title: Infect. Immun Volume: 79 Pages: 905-910
  • Peer Reviewed
• [Journal Article] Clostridium perfringens TpeL Glycosylates the Rac and Ras Subfamily Proteins (2011)
  • Author(s): Masahiro Nagahama
  • Journal Title: Infect.Immun. Volume: 79 Issue: 2 Pages: 905-910
  • DOI: 10.1128/iai.01019-10
  • Peer Reviewed
• [Journal Article] Cellular vacuolation induced by Clostridium perfringens epsilon-toxin (2011)
  • Author(s): Masahiro Nagahama
  • Journal Title: FEBS J. Volume: 278 Issue: 18 Pages: 3395-3407
  • DOI: 10.1111/j.1742-4658.2011.08263.x
  • Peer Reviewed
• [Journal Article] Clostridium perfringens iota-b induces rapid cell necrosis (2011)
  • Author(s): Masahiro Nagahama
  • Journal Title: Infect.Immun. Volume: 79 Issue: 11 Pages: 4353-4360
  • DOI: 10.1128/iai.05677-11
  • Peer Reviewed
• [Journal Article] Induction of neurite-outgrowth in PC12 cells by alpha-toxin from Clostridium perfringens (2011)
  • Author(s): Masataka Oda
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 411 Issue: 2 Pages: 241-246
  • DOI: 10.1016/j.bbrc.2011.06.103
  • Peer Reviewed
• [Journal Article] Clostridium perfringens TpeL Glycosylates the Rac and Ras Subfamily Proteins. (2011)
  • Author(s): Masahiro Nagahama
  • Journal Title: Infect.Immun. Volume: 79 Pages: 905-910
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of novel phosphate ester analogs as neutral sphingomyelinase inhibitors (2010)
  • Author(s): Imagawa H, Nagahama M, 他9名
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 20 Pages: 3868-3871
  • Peer Reviewed
• [Journal Article] Hemolysis induced by Bacillcereus sphingomyelinase (2010)
  • Author(s): Oda M, Nagahama M, 他4名
  • Journal Title: Biochem. Biophys. Auscta Volume: 1798 Pages: 1073-1080
  • Peer Reviewed
• [Journal Article] Hemolysis induced by Bacillus cereus sphingomyelinase. (2010)
  • Author(s): Masataka Oda
  • Journal Title: Biochim.Biophys.Acta Volume: 1798 Pages: 905-910
  • Peer Reviewed
• [Journal Article] Synthesis and evaluation of novel phosphate ester analogs as neutral sphingomyelinase inhibitors. (2010)
  • Author(s): Hiroshi Imagawa
  • Journal Title: Bioorg.Med.Chem.Lett. Volume: 20 Pages: 3868-3871
  • Peer Reviewed
• [Journal Article] Clostridium perfringens iota-toxin : structure and function (2009)
  • Author(s): Sakurai J, Nagahama M, Kobayashi K, 他2名
  • Journal Title: Toxins Volume: 1 Pages: 208-228
  • Peer Reviewed
• [Journal Article] Binding and internalization of Clostridium botulinum C2 toxin (2009)
  • Author(s): Nagahama M, 他8名
  • Journal Title: Infect. Immun Volume: 77 Pages: 5139-5148
  • Peer Reviewed
• [Journal Article] The inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by Clostridium perfingens alpha-toxin and its relation to alpha-rtoxin-induced intracellular ceramide generation (2009)
  • Author(s): Tumurkhuu G, Nagahama M, 他10名
  • Journal Title: Int. J. Med. Microbiol Volume: 299 Pages: 554-562
  • Peer Reviewed
• [Journal Article] The inhibition of lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide production by Clostridium perfringens α-toxin and its relation to α-toxin-induced intracellular ceramide generation (2009)
  • Author(s): Gantsetseg Tumurkhuu
  • Journal Title: Int.J.Med.Microbiol. 299 Pages: 554-562
  • Peer Reviewed
• [Journal Article] Binding and Internalization of Clostridium botulinum C2 Toxin (2009)
  • Author(s): Masahiro Nagahama
  • Journal Title: Infect.Immun. 77 Pages: 5139-5148
  • Peer Reviewed
• [Journal Article] Clostridium perfringens Iota-Toxin : Structure and Function (2009)
  • Author(s): Jun Sakurai
  • Journal Title: Toxins 1 Pages: 208-228
  • Peer Reviewed
• [Presentation] ウエルシュ菌ε毒素のMDCK細胞に対する空胞形成機構の解析 (2012)
  • Author(s): 永浜政博
  • Organizer: 第85日本細菌学会総会
  • Place of Presentation: 長崎市
  • Year and Date: 2012-03-28
• [Presentation] ウエルシュ菌ε毒素のMDCK細胞に対する空胞形成機構の解析 (2012)
  • Author(s): 永浜政博, 他
  • Organizer: 第85日本細菌学会総会
  • Place of Presentation: 長崎
• [Presentation] 永浜政博他ウエルシュ菌イオタb成分の細胞毒性機構の解析 (2012)
  • Author(s): 小林敬子
  • Organizer: 第85日本細菌学会総会
  • Place of Presentation: 長崎
• [Presentation] 永浜政博他ウエルシュ菌イオタIb成分の細胞毒性の検討 (2011)
  • Author(s): 小林敬子
  • Organizer: 文科省戦略的研究基盤形成支援事業第7回研究発表会
  • Place of Presentation: 徳島
  • Year and Date: 2011-12-22
• [Presentation] Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily (2011)
  • Author(s): 永浜政博
  • Organizer: IUMS2011 International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌市
  • Year and Date: 2011-09-07
• [Presentation] ウエルシュ菌のオリゴマー形成毒素について (2011)
  • Author(s): 永浜政博
  • Organizer: 文科省戦略的研究基盤形成支援事業第6回研究発表会
  • Place of Presentation: 徳島
  • Year and Date: 2011-07-09
• [Presentation] ボツリヌス菌C2毒素の細胞内侵入におけるTrkAの役割 (2011)
  • Author(s): 永浜政博
  • Organizer: 日本薬学会131年会
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] ウエルシュ菌イオタ毒素のIb成分による細胞毒性の解析 (2011)
  • Author(s): 田代遼, 小林敬子, 永浜政博, 他
  • Organizer: 第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 高松
• [Presentation] ウエルシュ菌イオタb成分の細胞毒性の解析 (2011)
  • Author(s): 小林敬子, 永浜政博, 他
  • Organizer: 第64回日本細菌学会中国・四国支部総会
  • Place of Presentation: 岡山
• [Presentation] Clostridium perfringens TpeL glycosylates the Rac and Ras subfamily (2011)
  • Author(s): M. Nagahama, K. Kobayashi, et al
  • Organizer: IUMS2011 International Un ion of Microbiological Societies 2011
  • Place of Presentation: Congress, Sapporo
• [Presentation] ウエルシュ菌α毒素のガングリオシド認識ドメインの同定 (2011)
  • Author(s): 小田真隆, 永浜政博, 他
  • Organizer: 第58回トキシンシンポジウム
  • Place of Presentation: 東京
• [Presentation] ウエルシュ菌β毒素によるTHP-1細胞のMAPKp38のリン酸化の解析 (2011)
  • Author(s): 渋谷昌弘, 永浜政博, 小林敬子, 他
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] ウエルシュ菌β毒素によるTHP-1細胞のMAPKp38のリン酸化 (2010)
  • Author(s): 渋谷昌弘, 永浜政博, 小林敬子, 他
  • Organizer: 文科省戦略的研究基盤形成支援事業第6回研究発表会
  • Place of Presentation: 徳島
  • Year and Date: 2010-12-22
• [Presentation] ウエルシュ菌イオタ毒素のIb成分の細胞に対する作用の解析 (2010)
  • Author(s): 永浜政博
  • Organizer: 日本薬学会 130年会
  • Place of Presentation: 桃太郎アリーナ(岡山市)
  • Year and Date: 2010-03-30
• [Presentation] ウエルシュ菌ε毒素のMDCK細胞F-アクチン増加効果の検討 (2010)
  • Author(s): 永浜政博, 小林敬子, 他
  • Organizer: BMB2010
  • Place of Presentation: 神戸
• [Presentation] ボツリヌス菌C2毒素の細胞内侵入におけるTrkAの役割 (2010)
  • Author(s): 樋口真美, 小林敬子, 永浜政博, 他
  • Organizer: 第49回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 米子
• [Presentation] ウエルシュ菌α毒素によるIL-8遊離とGM1の関係 (2010)
  • Author(s): 蕪道子, 永浜政博, 小林敬子, 他
  • Organizer: 第63回日本細菌学会中国・四国支部総会
  • Place of Presentation: 松山
• [Presentation] ウエルシュ菌イオタ毒素のIb成分の細胞に対する作用の解析 (2010)
  • Author(s): 永浜政博, 小林敬子, 他
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
• [Presentation] ボツリヌス菌C2毒素によるPI3K/Aktシグナル伝達系の活性化とエンドサイトーシスにおける役割 (2010)
  • Author(s): 小林敬子, 永浜政博, 他
  • Organizer: 第83日本細菌学会総会
  • Place of Presentation: 横浜
• [Presentation] ウエルシュ菌イオタ毒素のIb成分の細胞毒性の検討 (2009)
  • Author(s): 梅崎真理子, 永浜政博, 小林敬子, 他
  • Organizer: 文科省戦略的研究基盤形成支援事業第2回研究発表会
  • Place of Presentation: 徳島
  • Year and Date: 2009-12-19
• [Presentation] C型とD型ボツリヌス菌ホスホリパーゼCの酵素活性と生物活性 (2009)
  • Author(s): 阪口義彦, 小林敬子, 永浜政博, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ウエルシュ菌α毒素によるIL-8分泌とTrkAの関係 (2009)
  • Author(s): 蕪道子, 永浜政博, 他
  • Organizer: 第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 徳島
• [Presentation] ウエルシュ菌イオタ毒素のイオタb成分の培養細胞に対する作用 (2009)
  • Author(s): 梅崎真理子, 永浜政博, 小林敬子, 他
  • Organizer: 第62回日本細菌学会中国・四国支部総会
  • Place of Presentation: 広島
• [Book] Phosphorylation, Role of tyrosine kinase A receptor(TrkA) on pathogenicity of Clostridiumperfringens alpha-toxin (2012)
  • Author(s): Oda M, Nagahama M, Kobayashi K
  • Total Pages: 20
  • Publisher: InTech
• [Book] Glycosylation, Glycosylating toxin of Clostridiumperfringens (2012)
  • Author(s): Nagahama M, Kobayashi K
  • Total Pages: 20
  • Publisher: InTech
• [Book] 微生物胞子-制御と対策- (2011)
  • Author(s): 永浜政博
  • Total Pages: 380
  • Publisher: サイエンスフォーラム社
• [Book] 微生物胞子-制御と対策-嫌気性細菌 (2011)
  • Author(s): 永浜政博
  • Total Pages: 380
  • Publisher: サイエンスフォーラム社