Research of phage therapy and phage vaccine for bacterial infectious diseases.

• Project/Area Number: 25292182
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Rakuno Gakuen University
• Principal Investigator: IWANO Hidetomo 酪農学園大学, 獣医学群, 教授 (60382488)
• Co-Investigator(Kenkyū-buntansha): HIGUCHI Hidetoshi 酪農学園大学, 獣医学群, 教授 (00305905) ; HASHIGUCHI Shuhei 鹿児島大学, 理工学研究科, 助教 (40295275) ; HAGIWARA Katsuro 酪農学園大学, 獣医学群, 教授 (50295896) ; MAEHARA Seiya 酪農学園大学, 獣医学群, 准教授 (50438363)
• Co-Investigator(Renkei-kenkyūsha): TAMURA Yutaka 酪農学園大学, 獣医学群, 教授 (50382487)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 細菌感染症 / バクテリオファージ / 緑膿菌 / 黄色ブドウ球菌 / ファージセラピー / ワクチン / 薬剤耐性菌 / ウマ細菌性角膜炎 / 角膜炎 / 乳房炎

Outline of Final Research Achievements

Antimicrobial resistance in bacteria is a concern not only in veterinary medicine, but also in general, worldwide. There is a demand for new strategies to treat bacterial infections. In this research, we investigated the ‘phage therapy for bacterial infection’ and ‘phage vaccine’. We examined the use of phage to treat horse bacterial keratitis as a research of phage therapy. We isolated phages toward P. aeruginosa causing horse keratitis. The phages in this study could completely prevent the keratitis caused by P. aeruginosa in a keratitis mouse model. In the phage vaccine, we constructed phage with surface antigen of Mycoplasma.

Research Products

• [Journal Article] 1.Complete Genome Sequencing of the Broad-Host-Range Pseudomonas aeruginosa Bacteriophages ΦR18 and ΦS12-1. (2016)
  • Author(s): Takaaki Furusawa, Hidetomo Iwano, Hidetoshi Higuchi, Masaru Usui, Fumito Maruyama, Ichiro Nakagawa, Hiroshi Yokota, Yutaka Tamura.
  • Journal Title: Genome Announcements Volume: 4-3 Issue: 3 Pages: 1-2
  • DOI: 10.1128/genomea.00041-16
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bacteriophage can lyse antibiotic-resistant Pseudomonas aeruginosa isolated from canine diseases. (2016)
  • Author(s): Furusawa, T., Iwano, H., Higuchi, H., Yokota, H., Usui, M. and Tamura, Y.
  • Journal Title: J Vet Med Sci. Volume: in press
  • NAID: 130005159671
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cytokine mRNA profiling and the proliferative response of bovine peripheral blood mononuclear cells to Mycoplasma bovis. (2015)
  • Author(s): Gondaira, S., Higuchi, H., Iwano, H., Nakajima, K., Kawai, K., Hashiguchi, S., Konnai, S., and Nagahata, H.
  • Journal Title: Vet Immunol Immunopathol. Volume: 165 Pages: 45-43
  • Peer Reviewed
• [Journal Article] Cytokine mRNA profiling and the proliferative response of bovine peripheral blood mononuclear cells to Mycoplasma bovis. (2015)
  • Author(s): Gondaira S, Higuchi H, Iwano H, Nakajima K, Kawai K, Hashiguchi S, Konnai S, Nagahata H.
  • Journal Title: Vet Immunol Immunopathol. Volume: 165 Issue: 1-2 Pages: 45-53
  • DOI: 10.1016/j.vetimm.2015.03.002
  • Peer Reviewed / Open Access
• [Journal Article] Antimicrobial susceptibilities of Mycoplasma isolated from bovine mastitis in Japan. (2014)
  • Author(s): Kawai K, Higuchi H, Iwano H, Iwakuma A, Onda K, Sato R, Hayashi T, Nagahata H, Oshida T.
  • Journal Title: Anim Sci J. Volume: 85 Issue: 1 Pages: 96-99
  • DOI: 10.1111/asj.12144
  • Peer Reviewed / Open Access
• [Journal Article] Effect of dietary eugenol on xenobiotic metabolism and mediation of UDP-glucuronosyltransferase and cytochrome P450 1A1 expression in rat liver. (2014)
  • Author(s): Iwano H, Ujita W, Nishikawa M, Ishii S, Inoue H, Yokota H.
  • Journal Title: Int J Food Sci Nutr. Volume: 65 Issue: 2 Pages: 241-244
  • DOI: 10.3109/09637486.2013.845650
  • Peer Reviewed
• [Journal Article] Relationship between concentration of lingual antimicrobial peptide and somatic cell count in milk of dairy cows. (2013)
  • Author(s): Kawai K, Akamatsu H, Obayashi T, Nagahata H, Higuchi H, Iwano H, Oshida T, Yoshimura Y, Isobe N
  • Journal Title: Veterinary Immunology and Immunopathology Volume: 153(3-4) Issue: 3-4 Pages: 298-301
  • DOI: 10.1016/j.vetimm.2013.03.002
  • Peer Reviewed
• [Journal Article] Effects of vitamin E supplementation on cellular α-tocopherol concentrations of neutrophils in Holstein calves. (2013)
  • Author(s): Higuchi H, Ito E, Iwano H, Oikawa S, Nagahata H.
  • Journal Title: Can J Vet Res. Volume: 77 Pages: 120-125
  • Peer Reviewed
• [Journal Article] Mycoplasma species isolated from intramammary infection of Japanese dairy cows. (2013)
  • Author(s): Higuchi H, Gondaira S, Iwano H, Hirose K, Nakajima K, Kawai K, Hagiwara K, Tamura Y, Nagahata H.
  • Journal Title: Vet Rec. Volume: 172 Issue: 21 Pages: 557-557
  • DOI: 10.1136/vr.101228
  • Peer Reviewed
• [Journal Article] L-type amino acid transporter 1 (LAT1) expression in canine mammary gland tumors. (2013)
  • Author(s): Fukumoto, S., Hanazono, K., Komatsu, T., Iwano, H., Kadosawa, T. and Uchide, T.
  • Journal Title: J. Vet. Med. Sci. Volume: 75 Pages: 431-437
  • Peer Reviewed
• [Journal Article] A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): a pilot study in a canine model. (2013)
  • Author(s): Fukumoto, S., Hanazono, K., Dah-Renn, FU., Endo, Y., Kadosawa, T., Iwano, H. and Uchide, T
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 439 Issue: 1 Pages: 103-108
  • DOI: 10.1016/j.bbrc.2013.08.020
  • Peer Reviewed
• [Journal Article] L-type amino acid transporter 1 (LAT1): a new therapeutic target for canine mammary gland tumour. (2013)
  • Author(s): Fukumoto, S., Hanazono, K., Komatsu, T., Ueno, H., Kadosawa, T. Iwano, H. and Uchide, T.
  • Journal Title: Vet. J. Volume: 198 Issue: 1 Pages: 164-169
  • DOI: 10.1016/j.tvjl.2013.06.016
  • Peer Reviewed
• [Presentation] 次世代シーケンサーによる緑膿菌とバクテリオファージのゲノム解析 (2015)
  • Author(s): 古澤 貴章、岩野 英知、樋口 豪紀、臼井 優、丸山 史人、中川 一路、 横田 博、田村 豊
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 北里大学
  • Year and Date: 2015-09-07
• [Presentation] 競走馬の細菌性角膜炎に対するファージセラピーの検討 (2015)
  • Author(s): 岩野英知
  • Organizer: ファージセラピー臨床応用研究会
  • Place of Presentation: 東京工業大学
  • Year and Date: 2015-07-03
• [Presentation] 競走馬の細菌性角膜炎に対するファージセラピーの検討 (2015)
  • Author(s): 岩野英知 冷清水雄太郎 古澤貴章 樋口豪紀 萩原克郎 丹波秀和 片山芳也 木下優太 岩崎智仁 横田 博 田村 豊
  • Organizer: 日本獣医師会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2015-02-13 – 2015-02-15
• [Presentation] 競走馬の細菌性角膜炎に対するファージセラピーの検討 (2014)
  • Author(s): 岩野英知 冷清水雄太郎 古澤貴章 樋口豪紀 萩原克郎 丹波秀和 片山芳也 木下優太 横田 博 田村 豊
  • Organizer: 北海道獣医師会
  • Place of Presentation: 北海道大学
  • Year and Date: 2014-09-11
• [Presentation] 競走馬の細菌性角膜炎におけるファージセラピーの応用 (2014)
  • Author(s): 冷清水雄太郎 岩野英知 古澤貴章 樋口豪紀 萩原克郎 丹波秀和 片山芳也 木下優太 横田 博 田村 豊
  • Organizer: 日本獣医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2014-09-06 – 2014-09-08
• [Presentation] 乳房炎に対するファージセラピーの応用への課題 (2014)
  • Author(s): 岩野英知
  • Organizer: 乳房炎研究会
  • Place of Presentation: 旭川
  • Year and Date: 2014-08-09
• [Presentation] Prognostic significance of Caveolin-1 and urokinase plasminogen activator gene expression in canine mammary tumors (2013)
  • Author(s): Iwano, H., Sanae, A., Ebisawa, M., Endou, Y., Hirayama, K., Taniyama, H., Kadosawa, T., Yokota, H.
  • Organizer: 31st World Veterinary Congress
  • Place of Presentation: チェコ プラハ
• [Presentation] 黄色ブドウ球菌によるウシ乳房炎へのファージ療法応用に関する検討
  • Author(s): 岩野英知
  • Organizer: 薬物作用談話会
  • Place of Presentation: 江別 酪農大
• [Presentation] 緑膿菌性角膜炎に対するファージセラピーの有効性について
  • Author(s): 古澤貴章、岩野英知、冷清水健太郎、樋口豪紀、萩原克郎、横田博、田村豊
  • Organizer: 日本獣医学会
  • Place of Presentation: 岐阜
• [Presentation] 黄色ブドウ球菌によるウシ乳房炎へのファージ療法応用に関する検討
  • Author(s): 岩野英知、樋口豪紀、古澤貴章、田村豊
  • Organizer: 日本細菌学会総会
  • Place of Presentation: 千葉
• [Presentation] 緑膿菌性角膜炎に対するファージセラピーの有効性
  • Author(s): 古澤貴章、岩野英知、樋口豪紀、丹羽秀和、田村豊
  • Organizer: 日本細菌学会総会
  • Place of Presentation: 千葉