Development of novel method to eliminate Helicobacter pylori using bacteriolytic activity of bacteriophage

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kochi University
• Principal Investigator: MATSUZAKI Shigenobu Kochi University, 教育研究部・医療学系, 准教授 (00190439)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Hiroaki 高知大学, 教育研究部・医療学系 (90346560)
• Project Period (FY): 2008 – 2010
• Keywords: ピロリ菌 / ファージ / 除菌法

Research Abstract

Helicobacter pylori is a causative agent of gastritis and the stomach ulcer, and is also a risk factor of the stomach cancer. If H.pylori is detected at the patient's stomach, the elimination of it with the antibiotic agents is recommended. However, recent progress of antibiotic-resistance in H.pylori threatens the future of the elimination method. Therefore, we tried to get phage to develop the bacteriophage (phage) therapy system against H.pylori infection. As a result, a novel phage, φHP33, was isolated successfully. Phage φHP33 had a broad-host-range to many H.pylori strains and had strong lytic acitivity against them. Therefore, φHP33 is expected to be a good candidate as therapeutic phage for H.pylori infection.

Research Products

• [Journal Article] Presence of Merkel cell polyomavirus in Japanese cutaneous squamous cell carcinoma. (2011)
  • Author(s): Murakami M, Imajoh M, Ikawa T, Nakajima H, Kamioka M, Nemoto Y, Ujihara T, Uchiyama J, Matsuzaki S, Sano S, Daibata M.
  • Journal Title: J Clin Virol. 50 Pages: 37-41
  • Peer Reviewed
• [Journal Article] Characterization of lytic enzyme open reading frame 9 (ORF9) derived from Enterococcus faecalis bacteriophage phiEF24C. (2011)
  • Author(s): Uchiyama J, Takemura I, Hayashi I, Matsuzaki S, Satoh M, Ujihara T, Murakami M, Imajoh M, Sugai M, Daibata M.
  • Journal Title: Appl Environ Microbiol. J77 Pages: 580-585
  • Peer Reviewed
• [Journal Article] Isolation and characterization of a novel Staphylococcus aureus bacteriophage, φ MR25, and its therapeutic potential. (2010)
  • Author(s): Hoshiba H, Uchiyama J, Kato S, Ujihara T, Muraoka A, Daibata M, Wakiguchi H, Matsuzaki S.
  • Journal Title: Arch Virol. 155 Pages: 545-552
  • Peer Reviewed
• [Journal Article] The mechanical binding strengths of Helicobacter pylori BabA and SabA adhesins using an adhesion binding assay-ELISA, and its clinical relevance in Japan. (2010)
  • Author(s): Nishioka M, Takeuchi H, Con SA, Uehara Y, Nishimori I, Okumiya T, Kumon Y, Sugiura T.
  • Journal Title: Microbiol Immunol. 54 Pages: 442-451
  • Peer Reviewed
• [Journal Article] Clinical relevance of Helicobacter pylori babA2 and babA2/B in Costa Rica and Japan. (2010)
  • Author(s): Con SA, Takeuchi H, Nishioka M, Morimoto N, Sugiura T, Yasuda N, Con-Wong R.
  • Journal Title: World J Gastroenterol. 16 Pages: 474-478
  • Peer Reviewed
• [Journal Article] Blood kinetics of four intraperitoneally administered therapeutic candidate bacteriophages in healthy and neutropenic mice. (2009)
  • Author(s): Uchiyama J, Maeda Y, Takemura I, Chess-Williams R, Wakiguchi H, Matsuzaki S.
  • Journal Title: Microbiol Immunol. 53 Pages: 301-304
  • Peer Reviewed
• [Journal Article] Morphological and genetic analysis of three bacteriophages of Serratia marcescens isolated from environmental water. (2009)
  • Author(s): Matsushita K, Uchiyama J, Kato S, Ujihara T, Hoshiba H, Sugihara S, Muraoka A, Wakiguchi H, Matsuzaki S.
  • Journal Title: FEMS Microbiol Lett. 291 Pages: 201-208
  • Peer Reviewed
• [Journal Article] Characteristics of a novel Pseudomonas aeruginosa bacteriophage, PAJU2, which is genetically related to bacteriophage D3. (2009)
  • Author(s): Uchiyama J, Rashel M, Matsumoto T, Sumiyama Y, Wakiguchi H, Matsuzaki S.
  • Journal Title: Virus Res. 139 Pages: 131-134
  • Peer Reviewed
• [Journal Article] Role of bacterial and genetic factors in gastric cancer in Costa Rica. (2009)
  • Author(s): Con SA, Takeuchi H, Con-Chin GR, Con-Chin VG, Yasuda N, Con-Wong R.
  • Journal Title: World J Gastroenterol. 15 Pages: 211-218
  • Peer Reviewed
• [Journal Article] Antimicrobial activity of aminoreductone against Helicobacter pylori. (2009)
  • Author(s): Trang VT, Takeuchi H, Kudo H, Aoki A, Katsuno S, Shimamura T, Sugiura T, Ukeda H.
  • Journal Title: J Agric Food Chem. 57(23) Pages: 11343-11348
  • Peer Reviewed
• [Journal Article] Tail-associated structural protein gp61 of Staphylococcus aureus phage φMR11 has bifunctional lytic activity. (2008)
  • Author(s): Rashel M, Uchiyama J, Takemura I, Hoshiba H, Ujihara T, Takatsuji H, Honke K, Matsuzaki S.
  • Journal Title: FEMS Microbiol Lett. 284 Pages: 9-16
  • Peer Reviewed
• [Journal Article] In silico and in vivo evaluation of bacteriophage φ EF24C, a candidate for treatment of Enterococcus faecalis infections. (2008)
  • Author(s): Uchiyama J, Rashel M, Takemura I, Wakiguchi H, Matsuzaki S.
  • Journal Title: Appl Environ Microbiol. 74 Pages: 4149-4163
  • Peer Reviewed
• [Journal Article] A novel site-specific recombination system derived from bacteriophage φ MR11. (2008)
  • Author(s): Rashel M, Uchiyama J, Ujihara T, Takemura I, Hoshiba H, Matsuzaki S.
  • Journal Title: Biochem Biophys Res Commun. 368 Pages: 192-198
  • Peer Reviewed
• [Journal Article] Cloning, polymorphism, and inhibition of beta-carbonic anhydrase of Helicobacter pylori. (2008)
  • Author(s): Morishita S, Nishimori I, Minakuchi T, Onishi S, Takeuchi H, Sugiura T, Vullo D, Scozzafava A, Supuran CT.
  • Journal Title: J Gastroenterol. 43 Pages: 849-857
  • Peer Reviewed
• [Journal Article] Link between pericardial effusion and attenuation of QRS voltage in patients with hypothyroidism
  • Author(s): Yamanaka S, Kumon Y, Matsumura Y, Kamioka M, Takeuchi H, Sugiura T
  • Journal Title: Cardiology 116 Pages: 32-36
  • Peer Reviewed
• [Journal Article] CD40 signaling activated by Epstein-Barr virus promotes cell survival and proliferation in gastric carcinomaderived human epithelial cells.
  • Author(s): Imadome K, Shimizu N, Yajima M, Watanabe K, Nakamura H, Takeuchi H, Fujiwara S.
  • Journal Title: Microbes and infection 57 Pages: 11343-1348
  • Peer Reviewed
• [Presentation] Helicobacter pyloriにおける細胞分裂制御Minシステムの解析 (2011)
  • Author(s): 門田陽集、竹内啓晃、森本徳仁、公文義雄、杉浦哲朗
  • Organizer: 第56回 日本臨床検査医学会中国・四国支部総会
  • Place of Presentation: 岡山大学医学部(岡山県)
  • Year and Date: 20110205-20110206
• [Presentation] Helicobacter pylori細胞分裂関連遺伝子cdrAの機能とftsZとの関連性の解析 (2010)
  • Author(s): 門田陽集、竹内啓晃、森本徳仁、公文義雄、杉浦哲朗
  • Organizer: 第42回日本臨床検査自動化学会総会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 20101007-20101009
• [Presentation] 調製海洋深層水のin vivoにおけるHelicobacter pylori抑制効果 (2010)
  • Author(s): 川田雅彦、中川光司、池上良成、竹内啓晃、杉浦哲朗
  • Organizer: 第42回日本臨床検査自動化学会総会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 20101007-20101009
• [Presentation] ヘリコバクター・ピロリのSODに関する検討 (2010)
  • Author(s): 森下慶子、竹内啓晃、杉本千鶴子、島村智子、受田浩之、山本哲也、杉浦哲朗
  • Organizer: 第57回日本臨床検査医学会学術集会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 20100909-20100910
• [Presentation] Helicobacter pyloriに対するA22の増殖抑制 (2010)
  • Author(s): 西田愛恵、竹内啓晃、森本徳仁、杉本千鶴子、公文義雄、杉浦哲朗
  • Organizer: 第57回日本臨床検査医学会学術集会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 20100909-20100910
• [Presentation] In vivo effects of refined deep seawater (RDSW) against Helicobacter pylori (2010)
  • Author(s): 川田雅彦, 中川光司, 池上良成, 竹内啓晃, 杉浦哲朗
  • Organizer: 110^<th> ASM General Meeting
  • Place of Presentation: Convention center, San Diego, CA, (USA)
  • Year and Date: 20100523-20100528
• [Presentation] Identification of Helicobacter pylori outer membrane protein related to H.pylori-associated chronic idiopathic thrombocytopenic purpura (2010)
  • Author(s): N.Morimoto, H.Takeuchi, Y.Kumon, M.Tsuda, T.Taniguchi, T.Sugiura
  • Organizer: 110^<th> ASM General Meeting
  • Place of Presentation: Convention center, San Diego, CA, (USA)
  • Year and Date: 20100523-20100528
• [Presentation] Antimicrobial Activity of Aminoreductone against Helicobacter pylori (2010)
  • Author(s): Trang V.T., Takeuchi H., Shimamura T., Katsuno S., Sugiura T., Ukeda H., Kashiwagi T.
  • Organizer: 110^<th> ASM General Meeting
  • Place of Presentation: Convention center, San Diego, CA, (USA)
  • Year and Date: 20100523-20100528
• [Presentation] 黄色ブドウ球菌バクテリオファージ(ファージ)S13'及びS24-1の比較ゲノム解析による尾部吸着タンパク質の同定 (2010)
  • Author(s): 竹村伊代、内山淳平、氏原隆子、松崎茂展、村上雅尚、大畑雅典
  • Organizer: 第63回日本細菌学会中国・四国支部総会
  • Place of Presentation: 松山大学(愛媛県)
  • Year and Date: 2010-10-16
• [Presentation] 巨大黄色ブドウ球菌バクテリオファージの解析 (2010)
  • Author(s): 内山淳平、竹村伊代、氏原隆子、松崎茂展、村上雅尚、大畑雅典
  • Organizer: 第63回日本細菌学会中国・四国支部総会
  • Place of Presentation: 松山大学(愛媛県)
  • Year and Date: 2010-10-16
• [Presentation] 黄色ブドウ球菌バクテリオファージS13'及びS24-1の比較ゲノム解析と尾部吸着タンパク質の特徴付け (2010)
  • Author(s): 竹村伊代、内山淳平、氏原隆子、松崎茂展、村上雅尚、今城雅之、大畑雅典
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学蛋白質研究所(大阪府)
  • Year and Date: 2010-09-10
• [Presentation] T4関連ファージグループにおけるセラチアファージKSP90の系統学的位置 (2010)
  • Author(s): 竹村伊代、内山淳平、氏原隆子、松崎茂展、村上雅尚、今城雅之、大畑雅典
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学蛋白質研究所(大阪府)
  • Year and Date: 2010-09-10
• [Presentation] ファージ療法およびファージを利用する新しい細菌検出法の開発:高知大学の取り組み (2010)
  • Author(s): 内山淳平、松崎茂展、大畑雅典
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪大学蛋白質研究所(大阪府)
  • Year and Date: 2010-09-09
• [Presentation] 新規Serratia marcescens バクテリオファージKSP20, KSP90,およびKSP100の性状解析 (2010)
  • Author(s): 松下憲司, 内山淳平, 氏原隆子, 杉原重喜, 邑岡麻子, 大畑雅典, 松崎茂展
  • Organizer: 日本細菌学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-03-29
• [Presentation] 腸球菌ファージφEF24C由来溶菌酵素ORF9の解析 (2010)
  • Author(s): 内山淳平, 林幾江, 竹村伊代, 氏原隆子,竹内啓晃, 杉浦哲朗, 菅井基之, 大畑雅典, 松崎茂展
  • Organizer: 日本細菌学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-03-29
• [Presentation] 病院感染起因菌へのファージ療法の可能性 (2010)
  • Author(s): 松崎茂展
  • Organizer: ICD講習会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-03-26
• [Presentation] 新規Serratia marcescens バクテリオファージKSP90の性状解析 (2009)
  • Author(s): 松下憲司, 内山淳平, 氏原隆子, 杉原重喜, 邑岡麻子, 松崎茂展
  • Organizer: 日本細菌学会中国・四国支部総会
  • Place of Presentation: 広島大学(広島県)
  • Year and Date: 2009-10-16
• [Presentation] ヘリコバクター・ピロリ臨床分離株のSOD活性と臨床病態に関する検討 (2009)
  • Author(s): 森下慶子、(竹内啓晃, 他)
  • Organizer: 第56回日本臨床検査医学会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2009-08-28
• [Presentation] Helicobacter pylori膜蛋白とH.pylori関連慢性特発性血小板減少性紫斑病との関連性 (2009)
  • Author(s): 森本徳仁、(竹内啓晃, 他)
  • Organizer: 第15回日本ヘリコバクター学会学術総会
  • Place of Presentation: 東京サピアタワー(東京都)
  • Year and Date: 2009-06-25
• [Presentation] マウスにおける治療用バクテリオファージの血中動態の比較検討 (2009)
  • Author(s): 内山淳平、脇口宏、松崎茂展
  • Organizer: 日本感染症学会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2009-04-24
• [Presentation] Enterococcus faecalis ファージφEF24C由来溶菌酵素ORF9の溶菌活性 (2009)
  • Author(s): 竹村伊代, 内山淳平, 竹内啓晃, 杉浦哲朗, 松崎茂展
  • Organizer: 日本感染症学会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2009-04-24
• [Presentation] 血小板結合性を有するHelicobcter pylori低分子蛋白とH.pylori関連特発性血小板減少性紫斑病との関連性 (2009)
  • Author(s): 森本徳仁、(竹内啓晃, 他)
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-03-13
• [Presentation] 緑膿菌の新規溶原性バクテリオファージPAJU2の形態学的・遺伝学的解析 (2009)
  • Author(s): 内山淳平、松崎茂展
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-03-12
• [Presentation] ファージ療法:その可能性と課題 (2008)
  • Author(s): 松崎茂展
  • Organizer: 第2回バクテリオファージ研究会
  • Place of Presentation: 佐賀大学 菱の実会館(佐賀県)
  • Year and Date: 2008-09-11
• [Book] Free full text Related citations Chapter 17 : Inhibitors of Helicobacter pylori α and β-carbonic anhydrases as novel drugs for gastroduodenal diseases Drug Design of Zinc-Enzyme Inhibitors : Functional (2009)
  • Author(s): Nishimori I, et al
  • Total Pages: 359-374(計1022)
  • Publisher: Structural and Disease Applications
• [Patent(Industrial Property Rights)] 抗ピロリ菌組成物 (2009)
  • Inventor(s): 島村智子、竹内啓晃, 他
  • Industrial Property Rights Holder: 高知大学、日本ミルクコミュニティ(株)
  • Industrial Property Number: 特願2009-133754
  • Filing Date: 2009-06-03