Analysis of gene expression of Helicobacter pylori VacA

• Project/Area Number: 24659199
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including Mycology)
• Research Institution: Nagasaki University
• Principal Investigator: HIRAYAMA Toshiya 長崎大学, 熱帯医学研究所, 教授 (50050696)
• Co-Investigator(Kenkyū-buntansha): NAKANO Masayuki 長崎大学, 熱帯医学研究所, 助教 (60398005)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ヘリコバクター・ピロリ / VacA / 細菌毒素 / 毒素発現 / ピロリ菌 / 空胞化毒素 / 毒素産生 / 産生制御

Research Abstract

To define the stimulatory factor of VacA toxin production from Helicobacter pylori, we have examined the culture condition under controlling the concentration of some additions.
The liquid culture medium containing 5% bovine serum plus 0.1% cyclodextrin conferred highest bacterial growth and toxin production at 37oC for 72 h-cultivation in ambient air containing 5% CO2. We have also assessed whether bacterial cytosolic protein contributes gene expression and secretion of VacA focusing on interaction of mature and in mature toxin using anti-VacA antibody conjugated column chromatography.

Research Products

• [Journal Article] Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-induced Apoptosis (2013)
  • Author(s): Akazawa Y, Isomoto H, Matsushima K, Kanda T, Minami H, Yamaghchi N, Taura N, Shiozawa K, Ohnita K, Takeshima F, Nakano M, Moss J, Hirayama T, Nakao K.
  • Journal Title: PLoS One Volume: 8(12)
  • NAID: 120006986758
  • Peer Reviewed
• [Journal Article] 連載・私達の研究ピロリ菌感染におけるvacuolating cytotoxin(VacA)の役割に関する研究 (2013)
  • Author(s): 平山壽哉、中野政之
  • Journal Title: 化学療法の領域 Volume: vol.29(12) Pages: 117-123
• [Journal Article] VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets (2013)
  • Author(s): Satoh K, Hirayama T, Takano K, Suzuki-Inoue K, Sato T, Ohta M, Nakagomi J, Ozaki Y.
  • Journal Title: Thromb J Volume: 11 Pages: 23-23
  • Peer Reviewed
• [Journal Article] Helicobacter pyloriの病原因子 (2013)
  • Author(s): 中野政之,八尋錦之 助平山壽哉
  • Journal Title: 臨床と微生物 Volume: vol.40 Pages: 178-181
  • NAID: 10015590330
• [Journal Article] ピロリ菌の空胞化毒素VacAの病原性に関する新たな洞察 (2013)
  • Author(s): 中野政之、平山壽哉
  • Journal Title: 日本ヘリコバクター学会誌 Volume: vol.15 Pages: 12-21
• [Journal Article] VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets. (2013)
  • Author(s): Satoh K, Hirayama T, Takano K, Suzuki-Inoue K, Sato T, Ohta M, Nakagomi J, Ozaki Y
  • Journal Title: Thromb J. Volume: 11 Issue: 1 Pages: 23-30
  • DOI: 10.1186/1477-9560-11-23
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced apoptosis. (2013)
  • Author(s): Akazawa Y, Isomoto H, Matsushima K, Kanda T, Minami H, Yamaghchi N, Taura N, Shiozawa K, Ohnita K, Takeshima F, Nakano M, Moss J, Hirayama T, Nakao K.
  • Journal Title: PLoS One. Volume: 8
  • NAID: 120006986758
  • Peer Reviewed
• [Journal Article] Helicobacter pyloriの病原因子 (2013)
  • Author(s): 中野政之，八尋錦之助 平山壽哉
  • Journal Title: 臨床と微生物 Volume: 40 Pages: 178-181
  • NAID: 10015590330
• [Journal Article] 連載・私達の研究: ピロリ菌感染における vacuolating cytotoxin (VacA)の役割に関する研究 (2013)
  • Author(s): 平山壽哉、中野政之
  • Journal Title: 化学療法の領域 Volume: 29 Pages: 117-123
• [Journal Article] Reactive Oxygen Species-Induced Autophagic Degradation of Helicobacter pylori CagA Is Specifically Suppressed in Cancer Stem-like Cells (2012)
  • Author(s): Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, Nagano O, Matsuzaki J, Hibi T.
  • Journal Title: Cell Host Microbe Volume: 12 Pages: 764-777
  • Peer Reviewed
• [Journal Article] Low-densityLipoprotein Receptor-related Protein-1 (LRP1) Mediates Autophagy and ApoptosisCaused by Helicobacter pylori VacA (2012)
  • Author(s): Yahiro K, Satoh M, Nakano M, Hisatsune J, Isomoto H, Sap J, Suzuki H, Nomura F, Noda M, Moss J, Hirayama T.
  • Journal Title: J Biol Chem Volume: 287 Pages: 3104-3115
  • Peer Reviewed
• [Journal Article] Salmonella enterotoxin (Stn) regulates membrane composition and integrity (2012)
  • Author(s): Nakano M, Yamasaki E, Ichinose A, Shimohata T, Takahashi A, Akada JK, Nakamura K, Moss J, Hirayama T, Kurazono H.
  • Journal Title: Dis Model Mech Volume: 5 Pages: 515-521
  • NAID: 120006985703
  • Peer Reviewed
• [Journal Article] Interweaving microRNAs and proinflammatory cytokines in gastric mucosa with reference to H. pylori infection (2012)
  • Author(s): Isomoto H, Matsushima K, Inoue N, Hayashi T, Nakayama T, Kunizaki M, Hidaka S, Nakayama M, Hisatsune J, Nakashima M, Nagayasu T, Nakao K, Hirayama T.
  • Journal Title: J Clin Immunol Volume: 32 Pages: 290-299
  • Peer Reviewed
• [Journal Article] Reactive Oxygen Species-Induced Autophagic Degradation of Helicobacter pylori CagA Is Specifically Suppressed in Cancer Stem-like Cells (2012)
  • Author(s): Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, Nagano 0, Matsuzaki J, et al.
  • Journal Title: Cell Host & Microbe Volume: 12 Issue: 6 Pages: 764-777
  • DOI: 10.1016/j.chom.2012.10.014
  • Peer Reviewed
• [Journal Article] Low-density lipoprotein receptorrelated protein-1 (LRP-1) mediates autophagy and apoptosis caused by Helicobacter pyloriVacA (2012)
  • Author(s): Yahiro, K., Suzuki, H., et al.
  • Journal Title: J. Biol. Chem Volume: 287(37) Issue: 37 Pages: 31104-15
  • DOI: 10.1074/jbc.m112.387498
  • Peer Reviewed
• [Journal Article] Interweaving microRNAs and proinflammatory cytokines in gastric mucosa with reference to H. pylori infection (2012)
  • Author(s): Isomoto H. et al.
  • Journal Title: J Clin Immunol. Volume: 32 Issue: 2 Pages: 290-299
  • DOI: 10.1007/s10875-011-9626-3
  • Peer Reviewed
• [Journal Article] Salmonella enterotoxin (Stn) regulates membrane composition and integrity. (2012)
  • Author(s): Nakano M. et al.
  • Journal Title: Dis Model Mech. Volume: 5 Pages: 515-21
  • DOI: 10.1242/dmm.009324
  • NAID: 120006985703
  • Peer Reviewed
• [Presentation] ピロリ菌が産生するVacAはRPTPαを介してc-Srcを活性化する (2014)
  • Author(s): 中野政之、八尋錦之助、久恒順三、赤田純子、野田公俊、平山壽哉
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京都
• [Presentation] ピロリ菌がん蛋白質CagAを分解するオートファージを誘導するLRP1シグナル (2014)
  • Author(s): 津川仁、鈴木秀和、佐藤聡、三好佐和子、森英毅、正岡建洋、金井隆典、水島徹、井本正哉、平山壽哉
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京都
• [Presentation] LRP-1 mediates autophagy and apoptosis caused by Helicobacter pylori vacuolating cytotoxin (2013)
  • Author(s): Hirayama T, Nakano M, Noda M, Yahiro K.
  • Organizer: XXVIth International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer, VacA
  • Place of Presentation: Madrid
• [Presentation] Identification of Helicobacter pylori VacA in human lung and its effects on airway epitelial cells (2013)
  • Author(s): Nakashima S., Kakugawa T., Harada T., Hara S., Sakamoto N., Nakano M., Ishimatsu Y., Isomoto H., Mukae H., Kurazono H., Hirayama T., Kohno S.
  • Organizer: ERS Annual Congress 2013
  • Place of Presentation: Barcelona
• [Presentation] Low-density lipoprotein receptor-related protein-1 (LRP-1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA (2013)
  • Author(s): Hirayama T., Yahiro K., Nakano M., Noda M., Moss J.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan
• [Presentation] Hellcobacter pylori VacA cause autophagy and apoptosis Low-densitylipoprotein receptor-related protein-1 (LRP-1) (2013)
  • Author(s): Hirayama T.
  • Organizer: 5th Congress of European Microbiologists (FEMS 2013)
  • Place of Presentation: Leipzig
• [Presentation] VacAは小胞体ストレスの活性化により胃上皮細胞にアポトーシスを誘導する (2013)
  • Author(s): 赤澤祐子、磯本一、松島加代子、南ひとみ、山口直之、塩澤健、大仁田賢、竹島史直、平山壽哉、中尾一彦
  • Organizer: 第19回日本ヘリコバクター学会学術集会
  • Place of Presentation: 長崎市
• [Presentation] H.pylori感染胃粘膜の背景 : miRNA発現変動と炎症 (2013)
  • Author(s): 松島加代子、磯本一、赤澤祐子、大仁田賢、平山壽哉
  • Organizer: 第19回日本ヘリコバクター学会学術集会
  • Place of Presentation: 長崎市
• [Presentation] 胃MALTリンパ腫における拡大内視鏡所見の検討 (2013)
  • Author(s): 松島加代子、磯本一、赤澤祐子、大仁田賢、中尾一彦、平山壽哉
  • Organizer: 第19回日本ヘリコバクター学会学術集会
  • Place of Presentation: 長崎市
• [Presentation] 細胞内CagA安定性を規定する細胞表層LRP1のautophagy制御機構 (2013)
  • Author(s): 津川仁、鈴木秀和、佐谷秀行、松崎潤太郎、平田賢郎、福原誠一郎、岡田佐和子、正岡建洋、畠山昌則、平山壽哉、日比紀文
  • Organizer: 第19回日本ヘリコバクター学会学術集会
  • Place of Presentation: 長崎市
• [Presentation] ヘリコバクター・ピロリVacAのLRP1を介したオートファジーとアポトーシス誘導 (2013)
  • Author(s): 八尋錦之助、中野政之、野田公俊、平山壽哉
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張市
• [Presentation] Helicobacter pylori VacA cause autophagy and apoptosis Low-density lipoprotein receptor-related protein-1(LRP-1) (2013)
  • Author(s): Hirayama T.
  • Organizer: The 5th Congress of European Microbiologists (FEMS 2013)
  • Place of Presentation: Leipziger Messe GmbH, Leipzig, ドイツ
• [Presentation] Low-density lipoprotein receptor-related protein-1 (LRP-1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA. (2013)
  • Author(s): Hirayama T., Yahiro K., Nakano M., Noda M., Moss J.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: MiCo - Milano Congressi, Milan, イタリア
• [Presentation] Identification of helicobacter pylori VacA in human lung and its effects on airway epitelial cells (2013)
  • Author(s): Nakashima S., Kakugawa T., Harada T., Hara S., Sakamoto N., Nakano M., Ishimatsu Y., Isomoto H., Mukae H., Kurazono H., Hirayama T., Kohno S.
  • Organizer: ERS Annual Congress2013
  • Place of Presentation: FIRA BARCELONA, Barcelona, スペイン
• [Presentation] LRP-1 mediates autophagy and apoptosis caused by Helicobacter pylori vacuolating cytotoxin, VacA (2013)
  • Author(s): Hirayama T, Nakano M, Noda M, Yahiro K
  • Organizer: XXVIth International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer
  • Place of Presentation: Facultad de Medicina de la Universidad Autonoma de Madrid,Madrid, スペイン
• [Presentation] AUTOPHAGY CAUSING CAGA DEGRADATION IS TRIGGERED BY CYTOPLASMIC ACCUMULATION OF LOW-DENSITY LIPOPROTEIN RESEPTOR-RELATED PROTEIN-1(LRP1)IN GASTRIC EPITHELIAL CELLS INFECTED WITH H.PYLORI. (2013)
  • Author(s): Tugawa H., Matsuzaki J., Okada S., Fukuhara S., Mori H., Masaoka T., Sato A., Saya H., Hatakeyama M., Hirayama T., Suzuki H.
  • Organizer: Unites European Gastoroenterogy Week Berin 2013
  • Place of Presentation: Internationales Congress Centrum Berlin,Belrin, ドイツ
• [Presentation] ヘリコバクター・ピロリ感染症と毒素病態学的研究アプローチ (2012)
  • Author(s): 平山壽哉
  • Organizer: 第86回日本感染症学会総会
  • Place of Presentation: 長崎市
  • Year and Date: 2012-04-26
• [Presentation] Salmonella Stn regulates membrane composition and integrity (2012)
  • Author(s): Masayuki Nakano, Toshiya Hirayama
  • Organizer: The 6th Nagasaki Symposium on Tropical and Emerging Infectious Diseases & The 11thNagasaki-Singapore Medical Symposium
  • Place of Presentation: 長崎市
• [Presentation] Low-densitylipoprotein receptor-related protein-1 (LRP-1) mediates autophagy and apoptosis caused by Helicobacterpylori VacA (2012)
  • Author(s): Toshiya Hirayama and Masayuki Nakano
  • Organizer: The 6th Nagasaki Symposium on Tropical and Emerging Infectious Diseases & The 11th Nagasaki-Singapore Medical Symposium
  • Place of Presentation: 長崎市
• [Presentation] ER stress contributes to VacA induced gastric epithelial cell death (2012)
  • Author(s): Akazawa Y., Isomoto H., Matsushima K., Shiozawa K., Yamaguchi N., Ohnita K., Takeshima F., Hirayama T., Nakao K.
  • Organizer: UEGW 2012
  • Place of Presentation: Amsterdam
• [Presentation] Low-density lipoprotein receptor-related protein-1 (LRP-l) mediates autophagy and apoptosis caused by Helicobacter pylori VacA (2012)
  • Author(s): Kinnosuke Yahiro, Masayuki Nakano, Masatoshi Noda, Jan Sap, Joel Moss, Toshiya Hirayama
  • Organizer: EMBO 2012 meeting
  • Place of Presentation: Nice
• [Presentation] Evalution of the Function of Stn produced by salmonella (2012)
  • Author(s): Masayuki Nakano,Eiki Yamasaki,Takaaki Shimamoto, Akira Takahashi, Hisao Kurazono, Toshiya Hirayama
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路市
• [Presentation] Salmonella Stn regulates membrane composition and integrity (2012)
  • Author(s): Toshiya Hirayama and Masayuki Nakano
  • Organizer: 14th International Symposium on Microbial Ecology
  • Place of Presentation: Copenhagen
• [Presentation] A new insight into the function of of Stn roduced by Salmonella (2012)
  • Author(s): Nakano M., Yamasaki E., Shimohata T., Takahashi A., Moss J., Kurazono, H., Hirayama T.
  • Organizer: ASM2012 112th General Meeting
  • Place of Presentation: San Francisco
• [Presentation] Low-density lipoprotein receptor-related protein-1 (LRP-1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA. (2012)
  • Author(s): Yahiro K. et al.
  • Organizer: EMBO 2012 meeting
  • Place of Presentation: Nice Acropolis, Nice, France.