Studies on emesis-inducing signal receptor and molecular transfer mechanism of staphylococcal enterotoxin

• Project/Area Number: 21590475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Hirosaki University
• Principal Investigator: HU Dong-liang 弘前大学, 大学院・医学研究科, 准教授 (10333733)
• Co-Investigator(Kenkyū-buntansha): NAKANE Akio 弘前大学, 大学院・医学研究科, 教授 (30164239)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 病原性 / エンテロトキシ / ブドウ球菌エンテロトキシン / スーパー抗原 / 嘔吐活性 / メカニズム / 受容体 / 分子シグナル

Research Abstract

Staphylococcal enterotoxins (SEs) are superantigenic toxins and involved in human diseases including food poisoning and toxic shock syndrome. However, the role and mechanism in clinical symptoms of food poisoning remains poorly understood. In this study, house musk shrews were used to study the role and mechanism of SEs in food poisoning. Oral administration of SEA into shrews elicited a strong emetic response but no diarrhoeagenic symptom. SEA was injected into the intestinal loops of the animals did not induce exudation of fluid and consequent dilation of the intestinal segments. These results indicate that SEA has a strong superantigenic and emetic activity, but no diarrhoeagenic activity. We further investigated SEA receptor and emetic signal pathway in house musk shrews. Our results showed that pretreatment with a vanilloid receptor antagonist, capsazepine, significantly inhibited SEA-induced vomiting responses in the animals and the effect was shown in a dose-dependent manner. Immunofluorescence analysis showed that intestine of house musk shrew express vanilloid receptor and SEA co-localized with the cells expressing vanilloid receper. These results suggest that vanilloid receptor could play an important role in SEA-induced emetic response and this finding might be useful in prevention and treatment of staphylococcal food poisoning.

Research Products

• [Journal Article] Staphylococcal enterotoxin A has potent super-antigenic and emetic activities but not diarrheagenic activity (2012)
  • Author(s): Mina, E. K., Hu, D.-L., Omoe, K., Tsuji, T. and Nakane, A
  • Journal Title: Int.J.Med.Microbil Volume: 302(3) Pages: 88-95
  • Peer Reviewed
• [Journal Article] Submucosal mast cells in the gastrointestinal tract are a target of staphylococcal enterotoxin type A (2012)
  • Author(s): Ono, H., Nishizawa, M., Yamamoto, Y., Hu, D.-L., Nakane, A Shinagawa, K. and Omoe, K.
  • Journal Title: FEMS Immun. Med. Microbiol Volume: 64(1) Pages: 392-402
  • Peer Reviewed
• [Journal Article] Super-ntigenic oxin genes coexist with specific staphylococcal cassette chromosome mec genes in methicillin-esistant Staphylococcus aureus. Tohoku (2011)
  • Author(s): Hu, D.-L., Maina, E. K., Omoe, K. Inoue, F., Yasujima, M. and Nakane, A
  • Journal Title: J. Exp. Med Volume: 225 Pages: 161-169
  • Peer Reviewed
• [Journal Article] The superantigenic activity of toxic shock syndrome toxin-1 is resistant to heating and digestive enzymes (2011)
  • Author(s): Li, S.-J., Hu, D.-L., Maina, E. K., Shinagawa, K., Omoe, K. and Nakane, A
  • Journal Title: J. Appl. Microbiol Volume: 110 Pages: 729-736
  • Peer Reviewed
• [Journal Article] Superantigenic Toxin Genes Coexist with Specific Staphylococcal Cassette Chromosome mec Genes in Methicillin-Resistant Staphylococcus aureus (2011)
  • Author(s): Hu, D.-L., et al.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 225 Issue: 3 Pages: 161-169
  • DOI: 10.1620/tjem.225.161
  • NAID: 10030196029
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] The superantigenic activity of toxic shock syndrome toxin-1 is resistant to heating and digestive enzymes (2011)
  • Author(s): Li, S.-J., et al.
  • Journal Title: J.Appl.Microbiol. Volume: 110 Issue: 3 Pages: 729-736
  • DOI: 10.1111/j.1365-2672.2010.04927.x
  • Peer Reviewed
• [Journal Article] Mouse peptidoglycan recognition protein, PGLYRP-1, plays a role in host innate immune response against Listeria monocytogenes infection (2011)
  • Author(s): Osanai, A., et al.
  • Journal Title: Infect.Immun. Volume: 79 Issue: 2 Pages: 858-866
  • DOI: 10.1128/iai.00466-10
  • Peer Reviewed
• [Journal Article] High affinity of interaction between superantigen and TCR Vb molecules induces a high level and prolonged expansion of superantigen-reactive CD4^+ T cells (2010)
  • Author(s): Omoe, K., Nunomora, W., Kato, H., Li, Z.-J., Igarashi, O., Araaki, M., Sano, K., Ono, H., Abe, Y., Hu, D.-L., Nakane, A., Kiyono, H., Takakuwa, Y., Shinagawa, K., Uchiyama, T., Imanishi, K.
  • Journal Title: J. Bio. Chem Volume: 285(40) Pages: 30427-30435
  • Peer Reviewed
• [Journal Article] Role of interleukin-17A in cell-dediated protection against Staphylococcus aureus infection in mice immunized with fibrinogen-binding domain of clumping factor A (2010)
  • Author(s): Narita, K., Hu, D.-L., Mori, F., Wkabayashi, K., Iwakura, Y. and Nakane, A
  • Journal Title: Infect. Immun Volume: 78(10) Pages: 4999-5005
  • Peer Reviewed
• [Journal Article] Protective effect of glutathione S-transferase-fused mutant staphylococcal entero-toxin C against Staphylococcus aureus-induced bovine mastitis (2010)
  • Author(s): Cui, J.-C., Zhang, B.-J., Lin, Y.-C., Wang, Q.-K., Qian, A.-D., Nakane, A., Hu, D.-L. and Tong, G.-Z
  • Journal Title: Vet. Immun. Immunopath Volume: 135(5) Pages: 64-70
  • Peer Reviewed
• [Journal Article] The role of interleukin-17 in the protective effect of immunonization with clumping factor A against Staphylo-coccus aureus infection (2010)
  • Author(s): Narita, K. , Hu, D.-L., Nakane, A
  • Journal Title: Hirosaki Med. J Volume: 60(S) Pages: 238-244
  • Peer Reviewed
• [Journal Article] Protective effect of glutathione S-transferase-fused mutant staphylococcal enterotoxin C against Stavhvlococcus aureus-induced bovine mastitis. (2010)
  • Author(s): Cui, J.-C., et al.
  • Journal Title: Vet.Immun.Immunopath. Volume: 135 Pages: 64-70
  • Peer Reviewed
• [Journal Article] Immunization with nontoxic mutant staphylococcal enterotoxin A protectsagainst enterotoxin- induced emesis in house musk shrews. (2010)
  • Author(s): Hu, D.-L., et al.
  • Journal Title: Hirosaki Med.J. Volume: 60 Pages: 215-223
  • Peer Reviewed
• [Journal Article] High affinity of interaction between superantigen and TCR V13 molecules induces a high level and prolonged expansion of superantigen-reactive C De T cells (2010)
  • Author(s): Omoe, K., et al.
  • Journal Title: J.Bio.Chem. Volume: 285 Pages: 30427-30435
  • Peer Reviewed
• [Journal Article] Immuniza-tion with glutathione S-transferase-fused mutant staphylococcal entero toxin C protects against Staphylo-coccus aureus-induced mastitis in mouse model (2009)
  • Author(s): Zhang, B.-J., Cui, J.-C., Zhang, X., Qian, A.-D., Tong, G.-Z., Hu, D.-L.-, Nakane, A. and Wang Q.-K
  • Journal Title: Chn. J. Prev. Vet. Med. (Chinese Journal of Preventive Veterinary Medicine) Volume: 31(7) Pages: 557-562
  • Peer Reviewed
• [Journal Article] ブドウ球菌エンテロトキシンの嘔吐誘導活性 (2009)
  • Author(s): 中根明夫, 胡東良
  • Journal Title: 化学療法の領域 Volume: 25(5) Pages: 779-788
• [Journal Article] evelopment and evaluation of Staphylococcus aureus-induced mastitis model (2009)
  • Author(s): Zhang, B.-J., Cui, J.-C., Zhang, X., Qian, A.-D., Tong, G.-Z. , Hu, D.-L., Nakane, A. and Wang Q.-K
  • Journal Title: Chn. J. Prev. Vet. Med. (Chinese Journal of Preventive Veterinary Medicine) Volume: 31(5) Pages: 365-369
  • Peer Reviewed
• [Journal Article] Immunization with nontoxic mutant staphylococcal enterotoxin A, D227A, protects against enterotoxin-induced emesis in house musk shrews (2009)
  • Author(s): Hu, D.-L., Omoe, K., Shinagawa, K. and Nakane, A
  • Journal Title: J. Infect. Dis Volume: 199(3) Pages: 302-310
  • Peer Reviewed
• [Journal Article] c-di-GMP as a vaccine adjuvant protects against systemic methici-llin-resistant Staphylococcus aureus (MRSA) infection (2009)
  • Author(s): Hu, D.-L., Narita, K., Hyodo, M., Hayakawa, Y., Nakane, A. and Karao l i s, D. K
  • Journal Title: Vaccine Volume: 27 Pages: 4867-4873
  • Peer Reviewed
• [Journal Article] c-di-GMP as a vaccine adjuvant protects against systemic methicillin-resistant Staphylococcus aureus(MRSA)infection (2009)
  • Author(s): Hu, D.-L., et al.
  • Journal Title: Vaccine 27 Pages: 4867-4873
  • Peer Reviewed
• [Journal Article] Development and evaluation of Staphylococcus aureus-induced mastitis model. (2009)
  • Author(s): Zhang, B.-J., et al.
  • Journal Title: Chn.J.Prevent.Vet.Med. 31 Pages: 365-369
  • Peer Reviewed
• [Journal Article] Immunization with glutathione S-transferase-fused mutant staphylococcal enterotoxin C protects against Staphylococcus aureus-induced mastitis in mouse model. (2009)
  • Author(s): Zhang, B.-J., et al.
  • Journal Title: Chn.J.Prevent.Vet.Med. 31 Pages: 557-562
  • Peer Reviewed
• [Presentation] Vanilloid receptor plays an important role in staphylococcal enterotoxin A-induced emesis (2012)
  • Author(s): 胡東良,Maina, E. K.,重茂克彦,中根明夫
  • Organizer: 第85回日本細菌学会
  • Place of Presentation: 長崎
• [Presentation] Staphylococcal enterotoxin A has strong superantigenic and emetic activity but does not diarrheagenic activity (2012)
  • Author(s): Maina, E. K., Hu, D.-L., Omoe, K., Nakane, A
  • Organizer: 第85回日本細菌学会
  • Place of Presentation: 長崎
• [Presentation] 食中毒事例分離黄色ブドウ球菌におけるゲノム構成の解明 (2011)
  • Author(s): 佐藤祐介,小野久弥,胡東良,中根明夫,重茂克彦
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-19
• [Presentation] Toxic shock syndrome toxin-1 is resistant to heating and digestive enzymes on the superantigenic activity (2011)
  • Author(s): Hu, D.-L., Li, S.-J., Maina, E. K., Omoe, K., Nakane, A
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] ブドウ球菌エンテロトキシンAの消化管における標的細胞は肥満細胞である (2011)
  • Author(s): 小野久弥,廣瀬昌平,山本欣郎,胡東良,中根明夫,重茂克彦
  • Organizer: 第56回日本ブドウ球菌研究会
  • Place of Presentation: 高知
• [Presentation] Staphylococcus aureus pathogenicity islands解析法の確立とそれを用いた多様性解析 (2011)
  • Author(s): 佐藤祐介,小野久弥,胡東良,中根明夫,重茂克彦
  • Organizer: 第56回日本ブドウ球菌研究会
  • Place of Presentation: 高知
• [Presentation] Superantigenic activity of toxic shock syndrome toxin-1 is relatively resistant to heating and digestive enzymes compared with staphylococcal entetotoxin A (2011)
  • Author(s): Hu, D.-L, Li, S.-J., Maina, E.K., Omoe, K., Nakane, A
  • Organizer: IUMS, Sapporo
  • Place of Presentation: Japan.
• [Presentation] Staphylococcal enterotoxin A induces emetic but not diarrhoea response during Staphylococcus aureus food poisoning (2011)
  • Author(s): Maina, E. K., Hu, D.-L., Nakane, A
  • Organizer: IUMS, Sapporo
  • Place of Presentation: Japan
• [Presentation] ブドウ球菌エンテロトキシンAの粘膜上皮バリア通過機構の解明 (2011)
  • Author(s): 廣瀬昌平,小野久弥,山本欣郎,胡東良,中根明夫,重茂克彦
  • Organizer: 第65回日本細菌学会東北支部総会
  • Place of Presentation: 山形
• [Presentation] 食中毒原性黄色ブドウ球菌における特有のゲノム構成 (2011)
  • Author(s): 佐藤祐介,小野久弥,胡東良,中根明夫,重茂克彦
  • Organizer: 第65回日本細菌学会東北支部総会
  • Place of Presentation: 山形
• [Presentation] ブドウ球菌エンテロトキシンおよびエンテロトキシン様毒素産生に対する温度の影響 (2011)
  • Author(s): 佐藤明彦,長廻ゆりあ,山本裕紀,小野久弥,佐藤祐介,胡東良,中根明夫,重茂克彦
  • Organizer: 第65回日本細菌学会東北支部総会
  • Place of Presentation: 山形
• [Presentation] Staphylococcal enterotoxin A has strong superantigenic and emetic activity but does not diarrheagenic activity (2011)
  • Author(s): Maina, E. K., Hu, D.-L., Omoe, K., Nakane, A
  • Organizer: 第65回日本細菌学会東北支部総会
  • Place of Presentation: 山形
• [Presentation] メチシリン耐性黄色ブドウ球菌(MRSA)のSCCmecとスーパー抗原遺伝子の関連性 (2011)
  • Author(s): 胡東良,Edward K Maina,重茂克彦,中根明夫
  • Organizer: 第65回日本細菌学会東北支部総会
  • Place of Presentation: 山形
• [Presentation] Superantigenic activity of toxic shock syndrome toxin-1 is relatively resistant to heating and digestive enzymes compared with staphylococcal entetotoxin A. (2011)
  • Author(s): Hu, D.-L., et al
  • Organizer: IUMS
  • Place of Presentation: Sapporo, Japan
• [Presentation] Vaccination with a nontoxic mutant staphylococcal enterotoxin A, D227A, protects against enterotoxin-induced emesis in house musk shrews (2010)
  • Author(s): Hu, D.-L., Omoe, K., Sashinami, H., Shinagawa, K., Nakane, A
  • Organizer: The 10th Japan-Korea International Symposium on Micro-biology
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-03-26
• [Presentation] Omoe, K. temperiture dependent regulation of enterotoxin gene cluster related staphylococcal entero toxins production (2010)
  • Author(s): Sato, A., Nagasako, Y., Yamamoto, Y., Sato, Y., Ono, H. K., Hu, D.-L., Nakane, A
  • Organizer: IUMS, Sapporo
  • Place of Presentation: Japan
• [Presentation] ブドウ球菌エンテロトキシンAの標的細胞は肥満細胞である (2010)
  • Author(s): 小野久弥,広瀬昌平,山本欣郎,胡東良,中根明夫,重茂克彦
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] ブドウ球菌エンテロトキシンB遺伝子関連新規Staphylococcus arureus pathogenicity islandの同定 (2010)
  • Author(s): 佐藤祐介,小野久弥,胡東良,中根明夫,重茂克彦
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] The superantigenic activity of toxic shock syndrome toxin-1 is resistant to heating and digestive enzyme treatment (2010)
  • Author(s): Hu, D.-L. , Maina, E. K., Tomioka, Y., Li, S.-J., Narita, K., Osanai, A., Shinagawa, K., Omoe, K. and Nakane, A
  • Organizer: 14^<th> International Symposium on Staphy-lococci and Staphylococcal Infections
  • Place of Presentation: Bath, United Kingdom
• [Presentation] he role of IL-17A in the cell-mediated immunity induced by an immunization with clumping factor A against Staphylococcus aureus infection (2010)
  • Author(s): arita, K., Hu, D.-L., and Nakane, A
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
• [Presentation] ブドウ球菌エンテロトキシンAの消化管における動態と標的細胞の同定 (2010)
  • Author(s): 小野久弥,西澤雅人,山本欣郎,胡東良,中根明夫,重茂克彦
  • Organizer: 第64回日本細菌学会東北支部総会
  • Place of Presentation: 仙台
• [Presentation] 黄色ブドウ球菌エンテロトキシンB遺伝子を保有する新規Staphylococcus arureus pathogenicity islandの解析 (2010)
  • Author(s): 佐藤祐介,小野久弥,胡東良,中根明夫,重茂克彦
  • Organizer: 第64回日本細菌学会東北支部総会
  • Place of Presentation: 仙台
• [Presentation] 毒素性ショック症候群毒素のスーパー抗原活性は熱及びタンパク分解酵素に対し強い抵抗性を示す (2010)
  • Author(s): 胡東良,Edward K Maina,富岡義裕,李勝軍,成田浩司,長内理大,品川邦汎,重茂克彦,中根明夫
  • Organizer: 第64回日本細菌学会東北支部総会
  • Place of Presentation: 仙台
• [Presentation] ブドウ球菌エンテロトキシンB遺伝子を保有する新規Staphylococcus aureus pathogenicity islandsの解析 (2010)
  • Author(s): 佐藤祐介,小野久弥,胡東良,中根明夫,重茂克彦
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: 横浜
• [Presentation] ブドウ球菌エンテロトィンAの消化管における動態と標的細胞の解析 (2010)
  • Author(s): 小野久弥,重茂克彦,胡東良,中根明夫,品川邦汎
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: 横浜
• [Presentation] c-di-GMPはアジュバントとして黄色ブドウ球菌感染に対するワクチン効果を増強する (2010)
  • Author(s): 胡東良,成田浩司,中根明夫,David K. R. Karaolis
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: 横浜
• [Presentation] The superantigenic activity of toxic shock syndrome toxin-1 is resi stant to heating and digestive enzyme treatment (2010)
  • Author(s): Hu, D.-L., et al
  • Organizer: 14th International Symposium on Staphylococc i and Stavhvlococcal Infections (ISSSD
  • Place of Presentation: Bath, United Kingdom
• [Presentation] c-di-GMPはアジュバントとして黄色ブドウ球菌感染に対するワクチン効果を増強する. (2009)
  • Author(s): 胡東良, ら
  • Organizer: 第63回日本細菌学会東北支部総会
  • Place of Presentation: 盛岡
  • Year and Date: 2009-08-20
• [Presentation] ブドウ球菌エンテロトキシンAの消化管における動態 (2009)
  • Author(s): 小野久弥,重茂克彦,山本欣郎,胡東良,中根明夫,品川邦汎
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Vaccination with nontoxic mutant staphylococcal enterotoxin A, D227A, protects against enterotoxin-induced emesis in house musk shrews (2009)
  • Author(s): Hu, D.-L., Omoe, K., Sashinami, H., Shinagawa, K., Nakane, A.
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] 食品安全危害の新たな特徴と動物源性食品安全研究戦略 (2009)
  • Author(s): 胡東良,中根明夫
  • Organizer: 中国農業科学院動物源性食品安全研究センター設立式典並びに動物源性食品安全研究国際シンポジウム.特別講演
  • Place of Presentation: 上海
• [Presentation] ブドウ球菌エンテロトキシンAの腸管内動態の解析 (2009)
  • Author(s): 小野久弥,重茂克彦,山本欣郎,胡東良,中根明夫,品川邦汎
  • Organizer: 第148回日本獣医学会学術集会
  • Place of Presentation: 鳥取
• [Presentation] 無毒変異体ブドウ球菌エンテロトキシンAの免疫による嘔吐抑制効果 (2009)
  • Author(s): 胡東良,重茂克彦,差波拓志,品川邦汎,中根明夫
  • Organizer: 第56回日本毒素シンポジウム
  • Place of Presentation: 岐阜
• [Presentation] 新型ブドウ球菌エンテロトキシン(SEs)の食品中における産生量評価 (2009)
  • Author(s): 長廻ゆりあ,重茂克彦,稲垣華絵,山本裕紀,胡東良,中根明夫,品川邦汎
  • Organizer: 第63回日本細菌学会東北支部総会
  • Place of Presentation: 盛岡
• [Presentation] ブドウ球菌エンテロトキシンは熱及びタンパク分解酵素に強い抵抗性を示す (2009)
  • Author(s): 富岡義裕,胡東良,Edward Kithela Maina,成田浩司,重茂克彦,品川邦汎,中根明夫
  • Organizer: 第63回日本細菌学会東北支部総会
  • Place of Presentation: 盛岡
• [Presentation] c-di-GMPはアジュバントとして黄色ブドウ球菌感染に対するワクチン効果を増強する (2009)
  • Author(s): 胡東良,成田浩司,中根明夫,David K. R. Karaolis
  • Organizer: 第63回日本細菌学会東北支部総会
  • Place of Presentation: 盛岡