Development of prevention and treatment methods for infection by enterohemorrhagic Escherichia coli O157 based on bio-protect ive mechanisms

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590256
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: KOBAYSHI Hideyuki 産業医科大学, 医学部, 教授 (40148953)
• Co-Investigator(Kenkyū-buntansha): MORII Hiroyuki 産業医科大学, 医学部, 准教授 (60141743) ; FUJII Jun 鳥取大学, 医学部, 教授 (60271441) ; 大原 直也 岡山大学, 医歯薬総合研究科, 教授 (70223930)
• Project Period (FY): 2010 – 2012
• Keywords: 腸管出血性大腸菌 / ベロ毒素 / 感染症 / ワクチン / BCG / 遺伝子組み換え / 生理活性ペプチド

Research Abstract

We have developed a novel vaccine using a recombinant BCG expressing the verotoxin B-subunit. The immunized mice with this vaccine survived longer than the nonvaccinated mice, confirminging the validity of this vaccine.
On the other hand, the expression of various bioactive peptides in the brain microvascular endothelial cells was changed by verotoxin. The expression of cytokines was increased suggesting that the interaction between brain microvascular endothelial cells and the leukocytes was changed by verotoxin.

Research Products

• [Journal Article] Investigation of Encephalopathy Caused by Shiga Toxin 2c-Producing Escheriohia ooli Infection in Mice (2013)
  • Author(s): Amran M. Y., Fujii J., Suzuki S. 0., Kolling G. L.,Villanueva A. M.,Kainunla M., Kobayashi H., Kanleyanla H. and Yoshida S
  • Journal Title: PLoS One Volume: 8 Pages: e58959
  • DOI: 10.1371/journal.pone.0058959
  • Peer Reviewed
• [Journal Article] Antigen 85A and mycobacterial DNA-binding protein 1 are targets of immunoglobulin G in individuals with past tuberculosis (2013)
  • Author(s): Osada-Oka M, Tateishi Y, Hirayama Y, Ozeki Y, Niki M, Kitada S, Maekura R, Tsujimura K, Koide Y, Ohara N, Yamamoto T, Kobayashi K, Matsumoto S
  • Journal Title: Microbiol. Immunol Volume: 57 Pages: 30-37
  • DOI: 10.1111/j.1348-0421
  • Peer Reviewed
• [Journal Article] Protection by recombinant Bacillus Calmette-Guerin vaccine expression Shiga toxin 2B subunit against Shiga toxin producing Escherichia coli in mice (2012)
  • Author(s): Fujii J., Naito M., Yutsudo T., Heatherly D., Yamada T., Kobayashi H., Yoshida S. and Obrig T
  • Journal Title: Clin. Vac. Imnunol Volume: 19 Pages: 1932-1937
  • DOI: 10.1128/CVI.00473-12
  • Peer Reviewed
• [Journal Article] Current progress in tuberculosis and recombinant BCG vaccines (2012)
  • Author(s): Ohara N
  • Journal Title: J. Oral. Biosci Volume: 54 Pages: 92-95
  • URL: http://www. journaloforalbiosciences. Org/
  • Peer Reviewed
• [Journal Article] Lipidphenotype of two distinct subpopulations of Vayo ohaoteri um bovis Bacillus Calmette-Guerin Tokyo 172 substrain (2011)
  • Author(s): Naka T., Maeda S., Niki M., Ohara N., Yamamoto S.,Yano I.,Maeyama J.,Ogura H., Kobayashi K.,Fujiwara N
  • Journal Title: Biol. Chem Volume: 286 Pages: 44153-44161
  • Peer Reviewed
• [Journal Article] Suppressed induction of mycobacterial antigen-specific Th1-type CD4+Tcells in the lung after pulmonary mycobacterial infection (2010)
  • Author(s): Yahagi, A., Umemura, M., Tamura, T., Kariyone, A., Begum, M. D., Kawakami, K., Okamoto, Y., Hamada, S., Oshiro, K., Kohama, H., Arakawa, T., Ohara, N., Takatsu, K., Matsuzaki, G
  • Journal Title: Int. Immunol Volume: 22 Pages: 307-318
  • DOI: 10.1093/intimm/dxq010
  • Peer Reviewed
• [Journal Article] アグリン(キーワード解説) (2010)
  • Author(s): 小林英幸、森井宏幸
  • Journal Title: 日薬理誌 Volume: 135 Pages: 215-216
  • URL: http://www. pharmacol.or.jp/
  • Peer Reviewed
• [Presentation] Investigation of acute encephalopathy caused by Shiga toxin 2c-producing enterohemorrhagic E. coli 0157 in mice. (2012)
  • Author(s): Fujii J, Amran MY, Yoshida S
  • Organizer: U.S.-Japan cooperarive medical science program
  • Place of Presentation: Chiba University, Chiba Japan
  • Year and Date: 20121212-14
• [Presentation] Lipid Phenotypes of Two Distinct Subpopulations of Mycobacterium bovis Bacillus Calnlette-Guerin Tokyo 172 Substrain and their Host Responses (2012)
  • Author(s): Naka, T.,Maeda S.,Niki M., Ohara N.,Yamamoto S.,Yano I.,Maeyama J.,Ogura H.,Kobayashi K., Shibata M., and Fujiwara N
  • Organizer: American Society for Microbiology 112th General Meeting
  • Place of Presentation: Moscone Center, San Francisco, U.S.A
  • Year and Date: 20120616-19
• [Presentation] ストレプトマイシン依存性結核菌18bの依存性に関与する遺伝子変異の解明と新たなストレプトマイシン耐性を誘導する変異の発見 (2012)
  • Author(s): 佐藤法仁,山崎利雄,小林和夫,大原直也
  • Organizer: 第87回日本結核病学会総会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 20120510-11
• [Presentation] BCG Tokyo type I, II株の形態及び脂質分子の分布と機能 (2012)
  • Author(s): 藤原永年,中崇,前田伸司,柴田満,仁木満美子,大原直也,前山順一,矢野郁也,山本三郎
  • Organizer: 第87回日本結核病学会総会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 20120510-11
• [Presentation] Mycobacterium avium 亜種 (avium・hominissuis)間での酸性環境下における菌体外pH上昇に関与するアンモニア産生経路の研究 (2012)
  • Author(s): 花村菜.月,堀田康弘,小川賢二,八木哲也,西森敬,大原直也,藤原永年,前田伸司,山崎利雄,伊藤佐生智,瀧井猛将
  • Organizer: 第87回日本結核病学会総会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 20120510-11
• [Presentation] Risk factors for hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli infection in Japan (2012)
  • Author(s): Fujii J., Mizoue T., Nakada Y.,Ugajin S.,Naya Y.,Nakamura T.,Saitoh K.,Maruyama Y., Tada Y., Okabe N. and Yoshida S
  • Organizer: 8^<th> International Symposium on Shiga toxin (Verocytotoxin)- producing Escherichia coli infection
  • Place of Presentation: RAI Forum Complex, Amsterdam, The Netherlands
  • Year and Date: 20120506-09
• [Presentation] Effectiveness azithromycin and/or Chinese medicine in the early and late stage of Shiga toxin-producing Escherichia coli-infected mouse models (2012)
  • Author(s): Amran MY, Fujii J, Yoshida S
  • Organizer: 8^<th> International Symposiunl on Shiga toxin (Verocytotoxin)-producing Escherichia coli infection
  • Place of Presentation: RAI Forum Complex, Amsterdam, The Netherlands
  • Year and Date: 20120506-09
• [Presentation] 結核菌/BCGのストレプトマイシン耐性・依存性に関する新たな知見 (2012)
  • Author(s): 佐藤法仁,阿戸学,黒田誠,山崎利雄,松村隆之,関塚剛史,中山真彰,井上哲圭,本田尚子,土田耕三,小林和夫,大原直也
  • Organizer: 第82回実験結核研究会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 2012-05-09
• [Presentation] 抗酸菌のslidingmotilityと非貧食細胞への取り込みの関連性 (2012)
  • Author(s): 岡部真裕子,大原直也,藤原永年,中崇,阿戸学,小林和夫
  • Organizer: 第82回実験結核研究会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 2012-05-09