Mechanism for intracellular action of bacterial modulin from intracellular parasitic bacteria and application

• Project/Area Number: 18390134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyoto University
• Principal Investigator: MITSUYAMA Masao Kyoto University, 医学研究科, 教授 (10117260)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,130,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥2,730,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
• Keywords: 細胞内寄生菌 / 細菌性モジュリン / リステリア菌 / 結核菌 / サイトカイン / マクロファージ / 細胞内寄生性細菌

Research Abstract

細胞内寄生性細菌であるリステリア菌および結核菌が有する細菌性モジュリンの感染細胞に対する作用を、主としてサイトカイン応答を中心として解析した。リステリアの病原因子LLOが感染マクロファージ内で認識されインフラマソーム形成が起こってカスペース1が活性化される分子機構や、結核菌が宿主カスペース1活性化を誘導する過程にRD1 領域産物が関与することなど、多くの新たな知見が得られた。

Research Products

• [Journal Article] RD1 locus in Mycobacterium tuberculosis genome contributes 1 to the activation of caspase-1 via induction of potassium ion 2 efflux in infected macrophages Infect Immu (2009)
  • Author(s): Takeshi Kurenuma, Ikuo Kawamura*, Hideki Hara, Ryosuke Uchiyama, Sylvia Daim, Sita Ramyamali Dewamitta, Shunsuke Sakai, Kohsuke Tsuchiya, Takamasa Nomura and Masao Mitsuyama
  • Journal Title: submitted 6
  • Peer Reviewed
• [Journal Article] プロバイオテイクスと疾患はじめに (2009)
  • Author(s): 光山正雄
  • Journal Title: 医学のあゆみ 228(3) Pages: 197-197
  • Peer Reviewed
• [Journal Article] RD1 locus in Mycobacterium tuberculosis genome contributes to the activation of caspase-1 via induction of potassium ion efflux in infected macrphage. (2009)
  • Author(s): Tekashi Kurenuma, et al.
  • Journal Title: Infection and Immunity 77
  • Peer Reviewed
• [Journal Article] Critical involvement of pneumolysin in production of IL-1 α and caspase-1- dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 activation (2008)
  • Author(s): Shereen Shoma, Kohsuke Tsuchiya*, Ikuo Kawamura, Takamasa Nomura, Hideki Hara, Ryosuke Uchiyama, Sylvia Daim and Masao Mitsuyama
  • Journal Title: Infection and Immunity 76(4) Pages: 1547-1557
  • Peer Reviewed
• [Journal Article] Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, Listeriolysin O, after evasion from phagosome into the cytoplasm (2008)
  • Author(s): Hideki Hara, Kohsuke Tsuchiya, Takamasa Nomura, Ikuo Kawamura, Shereen Shoma and Masao Mitsuyama
  • Journal Title: J Immunol 180 Pages: 7859-7868
  • Peer Reviewed
• [Journal Article] 感染制御 (2008)
  • Author(s): 光山正雄
  • Journal Title: 第81回日本細菌学会総会最新の話題 4(4) Pages: 313-315
  • Peer Reviewed
• [Journal Article] Critical involvement of pneumolysin in production of IL-1α and caspase-1- dependent cytokines in infection with Streptococcus pneumoniae in vitro : a novel function of pneumolysin in caspase-1 activation. (2008)
  • Author(s): Shereen Shoma, et al.
  • Journal Title: Infection and Immunity 76 Pages: 1547-1557
  • Peer Reviewed
• [Journal Article] Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, Listeriolysin O, after evasion from phagosome into the cytoplasm. (2008)
  • Author(s): Hideki Hara, et al.
  • Journal Title: Journal of Immunology 180 Pages: 7859-7868
  • Peer Reviewed
• [Journal Article] Critical involvement of pneumolysin in production of IL-1 α and caspase-1-dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 (2008)
  • Author(s): Shereen Shoma, et. al.
  • Journal Title: Infection and Immunity 76 Pages: 1547-1557
  • Peer Reviewed
• [Journal Article] Dependency of Caspase-1 Activation Induced in Macrophages by Listeria monocytogenes on Cytolysin, Listeriolysin O, after Evasion from Phagosome into the Cytoplasm. (2008)
  • Author(s): Hideki Hara, et. al.
  • Journal Title: Journla of Immunology 180 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Mycobacterial mammalian cell entry protein 1A (Mce1A) contributes to induction of chemokine and proinflammtory cytokine expressions in A549 alveolar epithelial cells (2007)
  • Author(s): Juthaporn Kohwiwattanagun, Ikuo Kawamura, Takao Fujimura, and Masao Mitsuyama
  • Journal Title: Microbiol. Immunol 51(2) Pages: 253-261
  • Peer Reviewed
• [Journal Article] Mycobacterium tuberculosis H37Rv is capable of inhibiting necrosis of the infected macrophages via activation of caspase-9 (2007)
  • Author(s): Ryosuke Uchiyama, Ikuo Kawamura, Michiko Kawanishi, Kohsuke Tsuchiya, Takanari Tominaga, Taijin Kaku, Yutaka Fukasawa, Shunsuke Sakai, Takao Fujimura, Takamasa Nomura and Masao Mitsuyama
  • Journal Title: Infect. Immun 75(6) Pages: 2894-2902
  • Peer Reviewed
• [Journal Article] Irreversible loss of membrane-binding activity of Listeria-derived cytolysins in non-acidic conditions: a distinct difference from allied cytolysins produced by other Gram-positive bacteria (2007)
  • Author(s): Nomura Takamasa, Ikuo Kawamura , Chikara Kohda , Hisashi Baba , Yutaka Ito , Terumi Kimoto , Isao Watanabe, and Masao Mitsuyama
  • Journal Title: Microbiology 153(7) Pages: 2250-2258
  • Peer Reviewed
• [Journal Article] Cytolysin-dependent endosomal escape is required but not sufficient for the induction of Th1 immune response against Listeria infection: A distinct role for listeriolysin O as determined by cytolysin gene replacement (2007)
  • Author(s): Hideki Hara, Ikuo Kawamura, Takamasa Nomura, Takanari Tominaga, and Masao Mitsuyama
  • Journal Title: Infect Immun 75(8) Pages: 3791-3801
  • Peer Reviewed
• [Journal Article] RD1 region in mycobacterial genome is involved in induction of necrosis in the infected RAW264 cells via mitochondrial membrane damage and ATP depletion (2007)
  • Author(s): Taijin Kaku, Ikuo Kawamura, Ryosuke Uchiyama, Takeshi Kurenuma, and Masao Mitsuyama
  • Journal Title: FEMS icrobiology Letters 274(2) Pages: 189-195
  • Peer Reviewed
• [Journal Article] Vaccine and drug development (a review) Tuberculosis (2007)
  • Author(s): Masao Mitsuyama and David N. McMurray: Tuberculosis
  • Journal Title: 87
  • Peer Reviewed
• [Journal Article] 抗結核防御免疫と結核菌による免疫制御 (2007)
  • Author(s): 河村伊久雄、光山正雄
  • Journal Title: 実験医学25(20)増刊 105(3183)-111(3189)
• [Journal Article] 病原体の感染戦略の新知見化学療法の領域 (2007)
  • Author(s): 光山正雄
  • Journal Title: 結核菌の病原性発現機構はどこまでわかったか化学療法の領域 23(11) Pages: 1750-1756
  • Peer Reviewed
• [Journal Article] Mycobacterium tuberculosis H37Rv is capable of inhibiting necrosis of the infected macrophages via activation of caspase-9. (2007)
  • Author(s): Ryosuke Uchiyama, et. al.
  • Journal Title: Infection and Immunity 75 Pages: 2894-2902
  • Peer Reviewed
• [Journal Article] Irreversible loss of membranc-binding activity of Listeria-derived cytolysins in non-acidic conditions: a distinct difference from allied cytolysins produced by other Gram-positive bacteria. (2007)
  • Author(s): Nomura Takamasa, et. al.
  • Journal Title: Microbiology 153 Pages: 2250-2258
  • Peer Reviewed
• [Journal Article] Cytolysin-dependent endosomal escape is required but not sufficient for the induction of Th1 immune response against Listeria infection: A distinct role for listeriolysin O as determined by cytolysin gene replacement. (2007)
  • Author(s): Hideki Hara, et. al.
  • Journal Title: Infection and Immunity 75 Pages: 3791-3801
  • Peer Reviewed
• [Journal Article] RDl region in mycobacterial genome is involved in induction of necrosis in the infected RAW264 cells viamitochondrial membrane damage and ATP depletion. (2007)
  • Author(s): Tai jin Kaku, et. al.
  • Journal Title: FEMS Microbiology Letters 274 Pages: 189-195
  • Peer Reviewed
• [Journal Article] Tuberculosis: Vaccine and drug development(a review) (2007)
  • Author(s): Masao Mitsuyama, et. al.
  • Journal Title: Tuberculosis 87
  • Peer Reviewed
• [Journal Article] Critical involvement of domain 4 of listeriolysin 0 and allied bacterial cytolysins in temperature- and pH-dependent loss of cytolytic activity. (2007)
  • Author(s): Takamasa Nomura et al.
  • Journal Title: Microbiology 153(in press)
• [Journal Article] Mycobacterium tuberculosis H37Rv is capable of inhibiting necrosis of the infected macrophages via activation of caspase-9. (2007)
  • Author(s): Ryosuke Uchiyama et al.
  • Journal Title: Infection and Immunity 75(in press)
• [Journal Article] Mycobacterial mammalian cell entry protein lA (McelA)contributes to induction of chemokine and proinflammtory cytokineexpressions in A549 alveolar epithelial cells. (2007)
  • Author(s): Juthaporn Kohwiwattanagun et al.
  • Journal Title: Microbiology and Immunology 51(2) Pages: 253-261
• [Journal Article] Dependence of the lethal effect of pore-forming cytolysins on the cytolytic activity (2006)
  • Author(s): Isao Watanabe, Takamasa Nomura, Takanari Tominaga, Kazuhiro Yamamoto, Chikara Kohda, Ikuo Kawamura, and Masao Mitsuyama
  • Journal Title: Journal of Medical Microbiology 55 Pages: 505-510
  • Peer Reviewed
• [Journal Article] Limited contribution of Toll-like receptor (TLR) 2 and TLR4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans (2006)
  • Author(s): Kiwamu Nakamura, Kazuya Miyagi, Yoshinobu Koguchi, Yuki Kinjo, Kaori Uezu, Takeshi Kinjo, Morikazu Akamine, Jiro Fujita, Ikuo Kawamura, Masao Mitsuyama, Yoshiyuki Adachi, Naohito Ohno, Kiyoshi Takeda, Shizuo Akira, Akiko Miyazato, Mitsuo Kaku, and Kazuyoshi Kawakami
  • Journal Title: FEMS Immunology and Medical Microbiology 47(1) Pages: 148-154
  • Peer Reviewed
• [Journal Article] Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands: Involvement of masct cells and dendritic cells (2006)
  • Author(s): Kazuhiro Yamamoto, Ikuo Kawamura, Juichi Ito, and Masao Mitsuyama
  • Journal Title: Clinical and Experimental Allergy 36(6) Pages: 760-769
  • Peer Reviewed
• [Journal Article] Listeriolysin 0 derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice (2006)
  • Author(s): Kazuhiro Yamamoto, Ikuo Kawamura, Takanari Tominaga, Takamasa Nomura, Junichi Ito, and Masao Mitsuyama
  • Journal Title: Clinical and Experimental Immunology 144 Pages: 475-484
  • Peer Reviewed
• [Journal Article] Sustained-release vancomycin sheet may help to prevent prosthetic graft methicillin-resistant Staphylococcus aureus infection (2006)
  • Author(s): Hirose K, Marui A, Arai Y, Nomura T, Inoue S, Kaneda K, Kamitani T, Fujita M, Mitsuyama M, Tabata Y, and Komeda M
  • Journal Title: J. Vasc. Surg 44 Pages: 377-382
  • Peer Reviewed
• [Journal Article] Listeriolysin 0 derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice. (2006)
  • Author(s): Kazuhiro Yamamoto et al.
  • Journal Title: Clinical and Experimental Immunology 144 Pages: 475-484
• [Journal Article] Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands ligands : Involvement of masct cells and dendritic cells. (2006)
  • Author(s): Kazuhiro Yamamoto et al.
  • Journal Title: Clinical and Experimental Allergy 36 Pages: 760-769
• [Journal Article] Dependence of the lethal effect of pore-forming cytolysins on the cytolytic activity. (2006)
  • Author(s): Isao Watanabe et al.
  • Journal Title: Journal of Medical Microbiology 55 Pages: 505-510
• [Journal Article] Involvement of Toll-like receptor 2 signaling in the phagocytosis of Listeria monocytogenes by murine macrophages
  • Author(s): Yanna Shen, Ikuo Kawamura*, Takamasa Nomura, Kohsuke Tsuchiya, Hideki Hara, Huixin Qu, Sita R. Dewamitta, Takeshi Yamamoto, Sylvia Daim, Shunsuke Sakai, Takeshi Kurenuma and Masao Mitsuyama
  • Journal Title: Submitted to Cellular Microbiology
  • Peer Reviewed
• [Journal Article] Listeriolysin O, a major virulence factor of Listeria monocytogenes, is a novel Toll-like receptor (TLR) agonist recognized by TLR2 and TLR4
  • Author(s): Ikuo Kawamura, Chikara Kohda, Kohsuke Tsuchiya, Yutaka Ito, Terumi Kimoto, Takamasa Nomura and Masao Mitsuyama
  • Journal Title: submitted to J. Exp. Med. Submitted to J Immunol (in revision)
  • Peer Reviewed
• [Presentation] 細胞内寄生性リステリア病原因子による宿主免疫応答の誘導機構-生菌免疫の作用機序へのアプローチ- (2009)
  • Author(s): 光山正雄
  • Organizer: 第82回日本細菌学会
  • Place of Presentation: 名古屋市国際会議場
  • Year and Date: 2009-04-13
• [Presentation] 細胞内寄生性リステリア病原因子による宿主免疫応答の誘導機構 (2009)
  • Author(s): 光山正雄
  • Organizer: 第82回日本細菌学会(浅川賞受賞講演)
  • Place of Presentation: 名古屋市国際会議場
  • Year and Date: 2009-03-13
• [Presentation] Mycobacterium tuberculosis, Listeria monocytogenes and the host cytokine response (2008)
  • Author(s): Masao Mitsuyama
  • Organizer: The 11st Kyoto University International Symposium in Shanghai
  • Place of Presentation: 復旦大学上海医科大学ホール 中国
  • Year and Date: 2008-10-11
• [Presentation] Mycobacterium tuberculosis, Listeria monocytogenes and the host cytokine response (2008)
  • Author(s): 光山正雄
  • Organizer: The 11st Kyoto University International Symposium in Shanghai
  • Place of Presentation: 上海復旦大学上海医科大学ホール
  • Year and Date: 2008-10-11
• [Presentation] 細菌感染に対する免疫応答 (2008)
  • Author(s): 光山正雄
  • Organizer: 第38回日本耳鼻咽喉科感染症研究会
  • Place of Presentation: 島根県民会館ホール 松江市
  • Year and Date: 2008-09-05
• [Presentation] 細菌感染に対する免疫応答 (2008)
  • Author(s): 光山正雄
  • Organizer: 第38回日本耳鼻咽喉科感染症研究会(特別講演)
  • Place of Presentation: 松江市島根県民会館ホール
  • Year and Date: 2008-09-05
• [Presentation] Critical involvement of bacterial virulence factor in the host immune response to Listeria monocytogenes (2008)
  • Author(s): Masao Mitsuyama
  • Place of Presentation: 国際微生物学会議2008イスタンブール トルコ
  • Year and Date: 2008-08-08
• [Presentation] Critical involvement of bacterial virulence factor in the host immune response to Listeria monocytogenes (2008)
  • Author(s): 光山正雄
  • Organizer: IUMS2008 (Plenary Lecture)
  • Place of Presentation: トルコイスタンブール国際会議場
  • Year and Date: 2008-08-08
• [Presentation] 感染症を巡る最近の進歩 (2008)
  • Author(s): 光山正雄
  • Organizer: 第134回日本医学会シンポ
  • Place of Presentation: 日本医師会館大ホール 東京
  • Year and Date: 2008-07-17
• [Presentation] 感染症を巡る最近の進歩 (2008)
  • Author(s): 光山正雄
  • Organizer: 第134回目本医学会シンポジウム
  • Place of Presentation: 東京日本医師会館大ホール
  • Year and Date: 2008-07-17
• [Presentation] 細胞内寄生性細菌リステリアの病原因子と宿主免疫応答 (2008)
  • Author(s): 光山正雄
  • Organizer: 日本乳酸菌学会2008年度年次大会
  • Place of Presentation: 京都大学百周年時計台記念館ホール
  • Year and Date: 2008-07-14
• [Presentation] 細胞内寄生性細菌リステジアの病原因子と宿主免疫応答 (2008)
  • Author(s): 光山正雄
  • Organizer: 日本乳酸菌学会2008年度年次大会(特別講演)
  • Place of Presentation: 京都市京都大学百周年時計台記念館ホール
  • Year and Date: 2008-07-14
• [Presentation] The role of virulence factor of Listeria monocytogenes in the host response (2008)
  • Author(s): Masao Mitsuyama
  • Organizer: 81st Annual Congress of Bacteriology (Symposium1)
  • Place of Presentation: 京都市 国立京都国際会議場
  • Year and Date: 2008-03-24
• [Presentation] 細胞内寄生性細菌の細胞内生存戦略と感染宿主の免疫応答-細菌の病原因子と宿主防御機構のせめぎあい- (2008)
  • Author(s): 光山正雄
  • Organizer: 第42回大分感染症研究会
  • Place of Presentation: 大分全日空ホテル
  • Year and Date: 2008-02-07
• [Presentation] Mechanism in the requirement of listeriolysin O (LLO) for the induction of caspase-dependent cytokines in macrophages infected with Listeria monocytogenes (2007)
  • Author(s): Masao Mitsuyama
  • Organizer: In Minisymposium 73- Mechanism of protection against intracellular pathogens, Symposium Chair and oral presentation at 13th International Congress of Immunology
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 2007-08-25
• [Presentation] Mechanism in the requirement of listeriolysin O (LLO)for the induction of caspase-dependent cytokines in macrophages infected with Listeria (2007)
  • Author(s): Masao Mitsuyama
  • Organizer: 13th International Congress of Immunology (Symposium 73)
  • Place of Presentation: ブラジル国リオデジャネイロ 国際会議場
  • Year and Date: 2007-08-25
• [Presentation] Interaction of intracellular parasitic bacteria andhost defense system for the generationof Th1-dependent acquired immunity (2007)
  • Author(s): Masao Mitsuyama
  • Organizer: COE International Symposium 2007
  • Place of Presentation: Shiran-kaikan, Kyoto
  • Year and Date: 2007-06-02
• [Presentation] Interaction of intracellular parasitic bacteria and host defense system for the generation of Th1-dependent acquired immunity (2007)
  • Author(s): Masao Mitsuyama
  • Organizer: COE International Symposium 2007 in Kyoto
  • Place of Presentation: 京都市 京都大学芝蘭会館
  • Year and Date: 2007-06-02
• [Presentation] 医学(系学)部における微生物学教育のレーゾン・デートル (2007)
  • Author(s): 光山正雄
  • Organizer: 第80回日本細菌学会総会シンポジウムSS1 : 微生物学教育のあり方を考える
  • Place of Presentation: 大阪市 アジア太平洋トレードセンターATC ホール
  • Year and Date: 2007-03-28
• [Book] In Handbook of Listeria monocytogenes Ed by Dongyou Liu (2008)
  • Author(s): Masao Mitsuyama
  • Total Pages: 540
  • Publisher: Adaptive Immunity to Listeria monocytogenes
• [Book] Handbook of Listeria monocytogenes (2008)
  • Author(s): Masao Mitsuyama
  • Total Pages: 540
  • Publisher: CRC Press (New York)
• [Book] Listeria monocytogenes Handbook (2008)
  • Author(s): Masao Mitsuyama
  • Total Pages: 552
  • Publisher: Taylor & Francis, CRC Press
• [Book] 生体防御医学事典 (2007)
  • Author(s): 光山正雄
  • Total Pages: 365
  • Publisher: 朝倉書店
• [Book] 生体防御医学事典 (鈴木和男監修, 光山正雄他編著) (2007)
  • Author(s): 光山正雄
  • Total Pages: 365
  • Publisher: 朝倉書店
• [Book] 結核第1章A 結核菌の基礎(泉孝英監修 冨岡洋海編集) (2006)
  • Author(s): 光山正雄(分担執筆)
  • Total Pages: 458
  • Publisher: 医学書院(第1刷発行)
• [Book] メルクマニュアル (2006)
  • Author(s): 光山正雄
  • Publisher: 日経BP 社
• [Book] 結核(泉孝英監修 冨岡洋海編集 改訂第4版) (2006)
  • Author(s): 光山正雄(分担執筆)
  • Total Pages: 458
  • Publisher: 医学書院
• [Remarks]
  • URL: http://bisei15.mb.med.kyoto-u.ac.jp/index.html