Autophagy and strategy for intracellular multiplication of pathogenic bacteria

• Project/Area Number: 17390125
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Chiba University
• Principal Investigator: YAMAMOTO Tomoko Chiba University, 大学院・薬学研究院, 教授 (60110342)
• Co-Investigator(Kenkyū-buntansha): TAKAYA Akiko 千葉大学, 大学院・薬学研究院, 講師 (80334217) ; OYA Mai 千葉大学, 大学院・薬学研究院, 助教 (60456093) ; 友安 俊文 徳島大学, 大学院・ソシオテクノサイエンス研究部, 助教授 (20323404)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,660,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥1,260,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000); Fiscal Year 2005: ¥6,000,000 (Direct Cost: ¥6,000,000)
• Keywords: サルモネラ / オートファジー / アポトーシス / 宿主応答 / マクロファージ / ClpXP / SPI1 / OMV / ワクチン / O157 / 病原性 / 細胞内増殖能 / DnaK

Research Abstract

サルモネラは感染の初期にはマクロファージに細胞死を誘導して殺菌機構をエスケープし、中盤以降はファゴソームをSCVと呼ばれる細胞内オルガネラに成熟させ、増殖する。本研究において、サルモネラのSCV内増殖にはオートファジーに抵抗することが必須であることを明らにした。さらにSPI-1高発現サルモネラはマクロファージに大量のCaspase-3活性化を導き、アポトーシスを誘導することを見出した。マクロファージ内でのSPI-1発現制御は、サルモネラのLon proteaseが、SPI-1転写制御因子HilC, HilDを特異的に認識し分解することに基づくことを明らかにした。

Research Products

• [Journal Article] Coordinated regulation of expression of Salmonella Pathogenicity Island 1 and flagellar typeIII secretion systems by ATP-dependent ClpXP protease (2008)
  • Author(s): Kage, H., Takaya, A., Ohya, M., and Yamamoto, T.
  • Journal Title: J. Bacteriol 190 Pages: 2470-2478
• [Journal Article] Signal pathway in the salt-activated expression of the SPI1/typeIII secretion system in Salmonella enterica serovar Typhimurium (2008)
  • Author(s): Mizusaki, H. Takaya, A., Yamamoto, T. and Aizawa, S.
  • Journal Title: J. Bacteriol 190 Pages: 4624-4631
• [Journal Article] Detection of invA, spiC, sipC, invF, and hilA in Salmonella isolated from beef and poulty by dot blot hynridaization in Zambia (2008)
  • Author(s): Hang'ombe, B., Isogai, E., Mubita, C., Isogai, N., Silungwe, M., hisenga, C., Moonga, L., Mulenga, E., Yabe, J., Takaya, A., Yamamoto, T., Kurebayashi, Y. and Isogai, H.
  • Journal Title: Inter. J. App. Res. Vet. Med 6 Pages: 1-6
• [Journal Article] Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease. J (2008)
  • Author(s): Takaya, A., Tabuchi, F., Tsuchiya, H., Isogai, E. and Yamamoto, T.
  • Journal Title: Bacteriol 190 Pages: 4181-4188
• [Journal Article] σ^<32>-mediated negative regulation of Salmonella Pathogenicity Island 1 expression (2008)
  • Author(s): Matsui、M., Takaya,A. and Yamamoto, T.
  • Journal Title: J. Bacteriol 190 Pages: 6636-6645
• [Journal Article] サルモネラマクロファージ内生存戦略の分子機構 (2008)
  • Author(s): 高屋明子・山本友子
  • Journal Title: 感染炎症免疫 38 Pages: 282-289
• [Journal Article] 〓32-mediated negative regulation of.Salmonella pathogenicity island 1 expression (2008)
  • Author(s): Matsui, M., Takaya A. and Yamamoto, T.
  • Journal Title: Journal of Bacteriology 190 Pages: 6636-6645
  • Peer Reviewed
• [Journal Article] Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease (2008)
  • Author(s): Takaya, A., Tabuchi, F., Tsuchiya, H., Isogai, E. and Yamamoto, T.
  • Journal Title: Journal of Bacteriology 190 Pages: 4181-4188
  • Peer Reviewed
• [Journal Article] Coordinated regulation of expression of Salmonella pathogenicity island 1 and flagellar type III secretion systems by ATP-dependent ClpxP protease. (2008)
  • Author(s): Kage, H., Takaya, A., Ohya,M. and Yamamoto, T.
  • Journal Title: Coordinated regulation of expression of Salmonella pathogenicity island 1 and flagellar type III secretion systems by ATP-dependent ClpxP protease. 190 Pages: 2470-2478
  • Peer Reviewed
• [Journal Article] Signal pathoway in salt-activated expression of the Salmonella pathogenicity island 1 type III secretion systems by Salmonella enterica serovar Typhimurium. (2008)
  • Author(s): Mizusaki, H., Takaya, A., Yamamoto, T. and Aizawa, Shin-Ichi
  • Journal Title: Journal of Bacteriology 190 Pages: 4624-4631
  • Peer Reviewed
• [Journal Article] Coordinated regulation of expression of Salmonella pathogenicity island 1 and flagellar type III secretion systems by ATP-dependent ClpXP protease (2008)
  • Author(s): Kage, H, Takaya, A, Ohya, M, and Yamamoto, T
  • Journal Title: Journal of Bacteriology 190 Pages: 2470-2478
  • Peer Reviewed
• [Journal Article] An oral Saimonella vaccine promotes the down-regulation of cell surfaces Toll-like recetor 4(TLR4) and TLR2 expression in mice (2008)
  • Author(s): Eguchi, M, Sekiya, Y, Suzuki, M, Yamamoto, T and Matsui H
  • Journal Title: FEMS Immunol. Med. Microbiol 50 Pages: 300-308
  • Peer Reviewed
• [Journal Article] An oral Salmonella vaccine promotes the down-regulation of cell surface Toll-like receptor4(TLR4)and TLR2 expression in mice (2007)
  • Author(s): Eguchi, M., Sekiya, Y., Suzuki, M., Yamamoto, T., Matsui, H.
  • Journal Title: FEMS Immunol Med Microbiol 50 Pages: 300-308
• [Journal Article] Expressed Salmonella antigens within macrophages enhance the proliferation of CD4^+ and CD8^+ T lymphocytes via bystander dendritic cells (2007)
  • Author(s): Eguchi, M., Sekiya, Y., Kikuchi, Y., Takaya, A., Yamamoto, T., Matsui, H.
  • Journal Title: FEMS Immunol Med Microbiol 50 Pages: 411-420
• [Journal Article] Prevalence and Genetic Properties of Salmonella enterica Serovar Typhimurium Definitive Phage Type 104 Isolated from Rattus norvegicus and Rattus rattus House Rats in Yokohama City, Japan. Appl. Environ (2007)
  • Author(s): Yokoyama, E., Maruyama, S., Kabeya, H., Hara, S., Sata, S., Kuroki, T., and Yamamoto, T
  • Journal Title: Microbiol 73 Pages: 2624-2630
• [Journal Article] Expressed Saimonella antigens within macrophages enhance the proliferation of CD4+ and CD8+ T lymphocytes by means of bystander dendritic cells (2007)
  • Author(s): Eguchi, M, Sekiya, Y, Kikuchi, Y, Takaya, A, Yamamoto, T and Matsui H
  • Journal Title: FEMS Immunol. Med. Microbiol 50 Pages: 411-420
  • Peer Reviewed
• [Journal Article] The DnaK chaperone machinery converts the native FlhD_2C_2 hetero-tetramer into a functional transcriptional regulator of flagellar regulon expression in Salmonella (2006)
  • Author(s): Takaya, A., Matsui, M., Tomoyasu, T., Kaya, M., Yamamoto, T.
  • Journal Title: Mol. Microbiol 59 Pages: 1327-1340
• [Journal Article] Organization of Tn2610 containing two transposition modules (2006)
  • Author(s): Takaya, A., Watanabe, M., Yamamoto, T.
  • Journal Title: Antimicoriol. agents Chemother 50 Pages: 1143-1147
• [Journal Article] Bacterial strategies for escaping the bactericidal mechanisms by macrophage (2006)
  • Author(s): Yamamoto, T.
  • Journal Title: YAKUGAKUZASSHI 16 Pages: 1235-1243
  • NAID: 110004997527
• [Journal Article] 細菌がマクロファージ貪食と殺菌を回避するしくみ (2006)
  • Author(s): 山本友子・高屋明子
  • Journal Title: 蛋核酵 51 Pages: 118-124
• [Journal Article] Organization of Tn2610 containing two transposition modules (2006)
  • Author(s): A.Takaya, M.Watanabe, T.Yamamoto
  • Journal Title: Antimicrobial Agents and Chemotherapy 50 Pages: 1143-1147
• [Journal Article] The DnaK chaperone machinery converts the native FlhD2C2 hetero-tetramer into a functional transcriptional regulator of flagellar regulon expression in Salmonella. (2006)
  • Author(s): A.Takaya, M.Matsui, T.Tomoyasu, M.Kaya, T.Yamamoto
  • Journal Title: Molecular Microbiology 59 Pages: 1327-1340
• [Journal Article] The DnaK chaperone machinery converts the native FlhD_2C_2 hetero-tetramer into a functional transcriptional regulator of flagellar regulon expression in Salmonella (2006)
  • Author(s): Takaya, A., Matsui, M., Tomoyasu, T., Kaya, M., Tamamoto, T.
  • Journal Title: Molecular Microbiology 59・4 Pages: 1327-1340
• [Journal Article] De-repression of Salmonella Pathogenicity Island 1 genes within macrophages leads to rapid apoptosis via caspase-1- and caspase-3- dependent pathways (2005)
  • Author(s): Takaya A, Suzuki, A., Kikuchi, Y., Eguchi, M., Isogai, E., Tomoyasu, T., Yamamoto, T.
  • Journal Title: Cell Microbiol 7 Pages: 79-90
• [Journal Article] Degradation of the HilC and HilD regulator proteins by ATP-dependent Lon protease leads to down-regulation of Salmonella pathogenicity island 1 gene expression (2005)
  • Author(s): Takaya, A., Kubota, Y., Isogai, E., Yamamoto, T.
  • Journal Title: Mol. Microbiol 55 Pages: 839-852
• [Journal Article] ClpXP controls the expression of LEE genes in enterohaemorrhagic Escherichia coli (2005)
  • Author(s): Tomoyasu, T., Takaya, A., Handa, Y, Karata, K., Yamamoto, T.
  • Journal Title: FEMS Microbiol. Lett 254 Pages: 59-66
• [Journal Article] Evaluation of the Lon-deficient Salmonella strains as an oral vaccine candidate (2005)
  • Author(s): Kodama, C., Eguchi, M., Sekiya, Y., Yamamoto, T., Kikuchi, Y., Matsui, H
  • Journal Title: Microbiol. Immunol 49 Pages: 1035-1045
  • NAID: 10017088337
• [Journal Article] サルモネラの細胞内侵入と食細胞内寄生の分子機構 (2005)
  • Author(s): 山本友子・高屋明子
  • Journal Title: 日細菌誌 60 Pages: 375-387
• [Journal Article] Evaluation of the Lon-deficient Salmonella strain as an oral vaccine candidate (2005)
  • Author(s): Kodama, C., Eguchi, M., Sekiya, Y., Yamamoto, T., Kikuchi, Y., Matsui, H.
  • Journal Title: Microbiol.Immunology 49・12 Pages: 1035-1045
  • NAID: 10017088337
• [Journal Article] ClpXP controls the expression of LEE genes in enterohaemorrhagic Escherichia coli (2005)
  • Author(s): Tomoyasu, T., Takaya, A., Handa, Y., Karata, K., Yamamoto, T.
  • Journal Title: FEMS Microbiology Letters 253 Pages: 59-66
• [Presentation] Two functionally distinct TypeIII secretion systems for Salmonella pathogenesis (2009)
  • Author(s): Tomoko Yamamoto
  • Organizer: Japan-Mexico Workshop on "Pharmacobiology" and "Nanobiology"
  • Place of Presentation: Mexico City, Mexico
• [Presentation] Recognition of Hi1D, Salmonella Pathogenicity Islandl(SPI1)protein by Lon protease (2008)
  • Author(s): 大矢麻衣, 高屋明子, 山本友子
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 〓32 regurates Salmonella pathogenicity island l expression. (2008)
  • Author(s): 松井真理, 高屋明子, 山本友子
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 臨床分離肺炎球菌のケトライド耐性機構 (2008)
  • Author(s): 北川奈緒美, 高屋明子, 横山栄二, 山本友子
  • Organizer: 第91回日本細菌学会関東支部総会
  • Place of Presentation: 千葉
  • Year and Date: 2008-10-23
• [Presentation] サルモネラによるSPI1依存的マクロフアージカスパーゼー3活性化経 (2008)
  • Author(s): 小林里美, 高屋明子, 山本友子
  • Organizer: 第91回日本細菌学会関東支部総会
  • Place of Presentation: 千葉
  • Year and Date: 2008-10-23
• [Presentation] Control of host cell death by Salmonella pathogenicity island -1 typeIII secretion system (2008)
  • Author(s): 山本友子
  • Organizer: The ^<9th> Korea-Japan International Symposium on Microbiology 2008
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-10-17
• [Presentation] Salmonella Pathogenici ty Island1 タイプIII 蛋白分泌システムによるマクロフアージカスパーゼー8活性化制御 (2008)
  • Author(s): 高屋明子, 小林里美, 山本友子
  • Organizer: 第2回細菌学・若手コロッセウム
  • Place of Presentation: 湘南
  • Year and Date: 2008-08-04
• [Presentation] σ^<32> regulon regulates Salmonella pathogenicity island 1 expression (2008)
  • Author(s): 松井真理、高屋明子、山本友子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会合同大会
• [Presentation] Recognition of HilD, Salmonella Pathogenicity Island1(SPI1) protein, by Lon protease (2008)
  • Author(s): 大矢麻衣、高屋明子、山本友子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会合同大会
• [Presentation] Control of host cell death by Salmonella pathogenicity island-1 TypeIII secretion system (2008)
  • Author(s): Tomoko Yamamoto and Akiko Takaya
  • Organizer: The 9th Korea-Japan International Symposium on Microbiology
  • Place of Presentation: Seoul, Korea
• [Presentation] サルモネラ病原因子の発現と感染機構. ワークショップ (2008)
  • Author(s): 山本友子
  • Organizer: サルモネラ感染とワクチン開発
  • Place of Presentation: 第82回日本細菌学会総会
• [Presentation] Quorum sensing in Pseudonas aeruginosa is regulated by Lon protease (2007)
  • Author(s): Yamamoto T.
  • Organizer: 7th Intemational Conference on AAA Proteins
  • Place of Presentation: Cirencester,England
  • Year and Date: 2007-09-10
• [Presentation] 分子シャペロンDnaKによるサルモネラタイプIII蛋白質分泌機構制御 (2007)
  • Author(s): 高屋明子、松井真理、島崎稔、山本友子
  • Organizer: 第1回細菌学・若手コロッセウム
• [Presentation] AAA^+プロテアーゼLonによる腸管出血性大腸菌のタイプIIIエフェクター分泌制御機構 (2007)
  • Author(s): 山口陽、高屋明子、山本友子
  • Organizer: 第5回感染症沖縄フォーラム
• [Presentation] サルモネラのOMVによる病原性発現調節 (2007)
  • Author(s): 石川秀人、高屋明子、水之江義充、高出明美、磯貝恵美子、吉田眞一、 山本友子
  • Organizer: 第80回日本細菌学会総会
• [Presentation] Quorum sensing in Pseudomonas aeruginosa is regulated by Lon protease (2007)
  • Author(s): Yamamoto, T., and Takaya, A.
  • Organizer: 7^<th> International Conference on AAA Proteins
  • Place of Presentation: Cirencester, England
• [Presentation] The role of ClpXP protease in flagellum biogenesis of non-pathogenic and pathogenic E. coli (2007)
  • Author(s): Takaya, A., Kitagawa, R., Ohya, M., and Yamamoto, T.
  • Organizer: 7^<th> International Conference on AAA Proteins
  • Place of Presentation: Cirencester, England
• [Presentation] Function of DnaK/DnaJ chaperone machinery on the regulation of Salmonella typeIII secretion systems (2007)
  • Author(s): 高屋明子、大矢麻衣、山本友子
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会合同大会
• [Presentation] サルモネラSPI2非依存型食細胞内増殖機構 (2006)
  • Author(s): 高屋明子、島崎稔、山本友子
  • Organizer: 第79回日本細菌学会総会
• [Presentation] サルモネラのDnaKシャペロンによるHilA活性発現 (2006)
  • Author(s): 松井真理、高屋明子、山本友子
  • Organizer: 第79回日本細菌学会総会
• [Presentation] Type VI secretion system via outer membrane vesicle releases Salmonella PagC protein (2006)
  • Author(s): Takaya, A., Mizunoe, Y., Takade, A., Sashinami, H., Isogai, E., Nakane, A., Yoshida, S. and Yamamoto, T
  • Organizer: leading to attenuation of Salmonella virulence. ASM conference ; Protein Traffic in Prokaryotes
  • Place of Presentation: Iraklio Crete, Greece
• [Presentation] a novel and unique AAA+ member of Salmonella (2006)
  • Author(s): Takaya, A., Mogk, A. and Yamamoto, T. ClpV
  • Organizer: 41^<th> Joint Conference on Cholera and Other Bacterial Enteric Infections Panel
  • Place of Presentation: Gifu
• [Presentation] サルモネラのOMVを介したマクロファージ内増殖機構 (2005)
  • Author(s): 高屋明子、水之江義充、高出明美、磯貝恵美子、友安俊文、吉田真一、山本友子
  • Organizer: 第78回日本細菌学会総会
• [Presentation] サルモネラのDnaKシャペロンによるSPI1発現制御機構 (2005)
  • Author(s): 松井真理、高屋明子、友安俊文 山本友子
  • Organizer: 第78回日本細菌学会総会
• [Presentation] Activation of FlhD_2C_2 transcriptional master regulator of Salmonella flagellum biogenesis by DnaK chaperone machinery (2005)
  • Author(s): Takaya, A., Kaya, M., Tomoyasu, T. and Yamamoto, T
  • Organizer: Activation of FlhD_2C_2 transcriptional master regulator of Salmonella flagellum biogenesis by DnaK chaperone machinery. 105th American Society for Microbiology
  • Place of Presentation: General Meeting, Atlanta, USA
• [Presentation] Modulation of HilC and HilD transcriptional regulators for expression of SPI1 genes (2005)
  • Author(s): Oya, M., Takaya, A., Tomoyasu, T. and Yamamoto, T.
  • Organizer: in a complex manner. Cold Spring Harbor Meeting on Microbial pathogenesis & Host response
  • Place of Presentation: CSH, USA
• [Presentation] Lon protease regulates the induction of macrophage apoptosis for establishment of systemic Salmonella infection (2005)
  • Author(s): Yamamoto, T., Takaya, A. and Tomoyasu, T
  • Organizer: 6^<th> International Conference on AAA Proteins
  • Place of Presentation: Schloss Seggau, Austria
• [Book] 医科細菌学第4版 (2008)
  • Author(s): 山本友子
  • Total Pages: 430
  • Publisher: 南江堂
• [Book] 医科細菌学 (2008)
  • Author(s): 山本友子
  • Total Pages: 430
  • Publisher: 南江堂
• [Book] 薬科微生物学第5版 (2007)
  • Author(s): 山本友子
  • Total Pages: 318
  • Publisher: 丸善
• [Book] 薬科微生物学 (2007)
  • Author(s): 山本 友子
  • Total Pages: 318
  • Publisher: 丸善株式会社
• [Book] 微生物感染症学 (2005)
  • Author(s): 山本友子
  • Total Pages: 312
  • Publisher: 南山堂
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/bisei/index.html
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/bisei/index.html