Functional analysis of H. pylorivirulence factors for gastric disease induction through its endocytosis inhibition

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590725
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yamaguchi University
• Principal Investigator: AKADA Junko Yamaguchi University, 大学院・医学系研究科, 助教 (30346548)
• Co-Investigator(Kenkyū-buntansha): AOKI Hiroki 久留米大学, 循環器研究所, 准教授 (60322244) ; NAKAMURA Kazuyuki 山口大学, 大学院・医学系研究科, 教授 (90107748) ; NISHIKAWA Jun 山口大学, 大学院・医学系研究科, 講師 (00379950)
• Project Period (FY): 2008 – 2010
• Keywords: 上部消化管学(胃) / ピロリ菌

Research Abstract

Helicobacter pylori is a common pathogen that causes chronic gastritis and gastric cancer. Epidemiologic evidence suggests that H. pylori with both highly active vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), the major virulence factors, have an advantage in adapting to the host environment. However, the mechanistic relationship between VacA and CagA remains obscure. We report that CagA suppresses pinocytic endocytosis and the cytotoxicity of VacA in gastric epithelial cells. Our data suggest that H. pylori secretes VacA to attack distant host cells while injecting CagA into the gastric epithelial cells to which the bacteria are directly attached, thereby protecting these attached host cells from the cytotoxicity of VacA and creating a local ecological niche. This mechanism may allow H. pylorito balance damage to one population of host cells with the preservation of another, allowing for persistent infection.

Research Products

• [Journal Article] Helicobacter pylori CagA Inhibits Endocytosis of Cytotoxin VacA in Host Cells. (2010)
  • Author(s): Junko K.Akada, Hiroki Aoki, Yuji Torigoe, Takao Kitagawa, Hisao Kurazono, Hisashi Hoshida, Jun Nishikawa, Suji Terai, Masunori Matsuzaki, Toshiya Hirayama, Teruko Nakazawa, Rinji Akada, Kazuyuki Nakamura.
  • Journal Title: Dzsease Models & Mechanzsms 3 Pages: 605-617
• [Presentation] Hellcobacter pylorz CagA Inhibits Endocytosis of Cytotoxin VacA in Host Cells. (2010)
  • Author(s): Junko K. Akada, Hiroki Aoki, Toshiya Hirayama, Teruko Nakazawa, Rinji Akada, Kazuyuki Nakamura
  • Organizer: The American Society for Cell Biology (ASCB) 50th Annual Meeting
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA, U.S.A.
  • Year and Date: 20101211-20101215
• [Presentation] Helicobacter pylori CagA Inhibits Endocytosis of Cytotoxin VacA in Host Cells. (2010)
  • Author(s): Junko K. Akada, Hiroki Aoki, Toshiya Hirayama, Teruko Nakazawa, Rinji Akada, Kazuyuki Nakamura
  • Organizer: The 10th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awajishima Yumebutai International Conference Center, Hyogo, Japan
  • Year and Date: 20100907-20100910
• [Presentation] ピロリ菌CagAは細胞膜VacA受容体RPTR・のエンドサイトーシスを阻害する (2010)
  • Author(s): 赤田純子、中澤晶子、平山壽哉、中村和行
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: パシフィコ横浜国際会議場、横浜
  • Year and Date: 20100327-20100329
• [Presentation] Helicobacter pylori CagA inhibit VacA endocytosis and vacuolation during infection. (2009)
  • Author(s): Junko K. Akada, Hiroki Aoki, Hisao Kurazono, Toshiya Hirayama, Teruko Nakazawa Kazuyuki Nakamura
  • Organizer: 15th International Workshop on Campylobacter, Helicobacter, and Related organisms (CHRO2009)
  • Place of Presentation: Toki-Messe, Niigata, Japan.
  • Year and Date: 20090902-20090905
• [Presentation] CagAによる細胞膜VacA受容体RPTP・のエンドサイトーシス阻害 (2009)
  • Author(s): 赤田純子、中澤晶子、平山壽哉、中村和行
  • Organizer: 第15回日本ヘリコバクター学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス、東京
  • Year and Date: 20090625-20090626
• [Presentation] Helicobacter pylori CagA inhibits VacA endocytosis during infection. (2009)
  • Author(s): 赤田純子、倉園久生、平山壽哉、中澤晶子、中村和行
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋市国際会議場、名古屋
  • Year and Date: 20090312-20090314
• [Presentation] ピロリ菌病原エフェクター蛋白質CagAは宿主細胞において細胞空胞化毒素VacAのエンドサイトーシスと細胞障害を低減する (2008)
  • Author(s): 赤田純子、青木浩樹、平山壽哉、中村和行
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸ポートアイランド、神戸
  • Year and Date: 20081209-20081212
• [Presentation] Helicobacter pylori CagA inhibits endocytosis in yeast and gastric epithelial cells. (2008)
  • Author(s): Junko K. Akada, Hiroki Aoki, Teruko Nakazawa, Rinji Akada, Kazuyuki Nakamura
  • Organizer: 8^<th> International Workshop on Pathogenesis and Host Response in Helicobacter Infections LO-skolen
  • Place of Presentation: Helsingor, Denmark
  • Year and Date: 20080702-20080705
• [Presentation] 培養細胞感染系においてCagAはVacAの細胞空胞化を抑制する (2008)
  • Author(s): 赤田純子、西川潤、中澤晶子、平山壽哉、中村和行
  • Organizer: 第14回日本ヘリコバクター学会
  • Place of Presentation: 神戸、神戸ポートピアホテル
  • Year and Date: 20080626-20080628
• [Book] 微生物増殖学の現在・未来(第11章 11-3 医学系の計数培養)(福井作蔵・秦野琢之編) (2008)
  • Author(s): 赤田純子
  • Total Pages: 306-310
  • Publisher: 地人書館東京
• [Remarks] ホームページ等 なし
• [Patent(Industrial Property Rights)] 自己抗体の検出方法 (2010)
  • Inventor(s): 赤田純子、中村和行、蔵満保宏
  • Industrial Property Rights Holder: 山口大学
  • Industrial Property Number: 特許,特願2010-188841
  • Filing Date: 2010-08-25