Elucidation of the new pathogenic mechanism of staphylococcal superantigen toxin and its application in the next generation vaccine

• Project/Area Number: 16H05030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Kitasato University
• Principal Investigator: Hu Dong-Liang 北里大学, 獣医学部, 教授 (10333733)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: ブドウ球菌 / スーパー抗原 / 病原機構 / ワクチン / 肥満細胞 / 感染機構 / 受容体 / エンテロトキシン / 病原性 / 生物活性 / 病原因子 / スーパー抗原毒素 / 毒素

Outline of Final Research Achievements

In this study, we analyzed the adhesion and binding between Staphylococcus aureus and host cells, the receptor and its molecular signal transduction mechanism at the molecular and cellular levels, using mutant toxins and strains lacking the superantigen activity. In addition, we elucidated the mechanism of persistent infectivity of S. aureus, and the protective effect of the mutant toxin immunization at the organism level. Furthermore, the protective antigen for next-generation vaccine against staphylococcal infection have be searched, suggesting that it could be applied to a new preventive method against S. aureus infection.

Academic Significance and Societal Importance of the Research Achievements

本研究は，ブドウ球菌と宿主細胞との付着・結合性，レセプターと分子シグナル伝達機序を解明し，生体での持続感染性および毒素免疫による感染防御機序を解析した．また，ブドウ球菌感染に対する次世代ワクチン開発に応用可能な抗原を検索した．本研究で得られる知見は動物のブドウ球菌感染症のみならず，人のHA-MRSAやCA-MRSAの感染制御にも貢献するものであると考えられる．

Research Products

• [Journal Article] Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A (SEA) evokes vomiting reflex in common marmoset (2019)
  • Author(s): Ono, H, K., Hirose, S., Narita, K., Sugiyama, M., Asano, K., Hu, D.-L., Nakane A.
  • Journal Title: PloS Pathogens. Volume: 21
  • Peer Reviewed
• [Journal Article] IL-10 produced by mutant toxic shock syndrome toxin-1 vaccine-induced memory T cells downregulates IL-17 production and abrogates the protective effect against Staphylococcus aureus infection (2019)
  • Author(s): Narita, K., Hu, D.-L., Asano, K. Nakane, A.
  • Journal Title: Infect. Immun. Volume: 87 Issue: 10
  • DOI: 10.1128/iai.00494-19
  • Peer Reviewed
• [Journal Article] Staphylococcal enterotoxin C is an important virulence factor for mastitis. (2019)
  • Author(s): Fang, R., Cui, J., Cui, t., Guo, H., Ono, H.K., Park, C.H., Okamura, M., Nakane, A. and Hu, D.-L.
  • Journal Title: Toxins (Basel) Volume: 11 Issue: 3 Pages: 141-141
  • DOI: 10.3390/toxins11030141
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of An Immunoassay for Detection of Staphylococcal Enterotoxin-like J, A Non-Characterized Toxin. (2018)
  • Author(s): Ono, H. K., Hachiya, N., Suzuki, Y., Naito, I., Hirose, S., Asano, K., Omoe, K., Nakane, A. and Hu, D.-L.,
  • Journal Title: Toxins (Basel) Volume: 10 Issue: 11 Pages: 485-485
  • DOI: 10.3390/toxins10110458
  • Peer Reviewed / Open Access
• [Journal Article] Biological characteristics of staphylococcal enterotoxin Q and its potential risk for food poisoning (2017)
  • Author(s): Hu D.-L.、Ono H.K.、Isayama S.、Okada R.、Okamura M.、Lei L.C.、Liu Z.S.、Zhang X.-C.、Liu M.Y.、Cui J.C.、Nakane A.
  • Journal Title: Journal of Applied Microbiology Volume: 122 Issue: 6 Pages: 1672-1679
  • DOI: 10.1111/jam.13462
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The emetic activity of staphylococcal enterotoxins, SEK, SEL, SEM, SEN and SEO, in house musk shrew (Suncus murinus). (2017)
  • Author(s): Ono, H. K., Hirose, S., Naito, I., Sato’o, Y., Asano, K., Hu, D.-L., Omoe, K., Nakane, A.
  • Journal Title: Microbiol. Immun. Volume: 61 Issue: 1 Pages: 12-16
  • DOI: 10.1111/1348-0421.12460
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Goblet cells are involved in translocation of staphylococcal enterotoxin A in the intestinal tissue of house musk shrew (Suncs murinus) (2016)
  • Author(s): Hirose S, Ono HK, Omoe K, Hu DL, Asano K, Yamamoto Y, Nakane A
  • Journal Title: Journal of Applied Microbiology Volume: 120 Issue: 3 Pages: 781-789
  • DOI: 10.1111/jam.13029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A evokes vomiting reflex in common marmoset (2019)
  • Author(s): 小野久弥，廣瀬昌平, 成田浩司, 杉山真言, 浅野クリスナ, 胡 東良, 中根明夫
  • Organizer: 第92回日本細菌学会総会, 札幌.
• [Presentation] Staphylococcal Enterotoxin C is an Important Virulence Factor for Mastitis (2019)
  • Author(s): Hu, D.-L., Fang, R., Guo, H., Ono, H.K., Okamura, M., Park, C., Nakane, A., Cui, J.
  • Organizer: ASM microbe 2019, San Francisco, USA.
  • Int'l Joint Research
• [Presentation] 鶏の感染症と食鳥肉の衛生～特にブドウ球菌とブドウ球菌症について ～ (2019)
  • Author(s): 胡 東良
  • Organizer: 青森県獣医師会・食鳥検査技術研修会, 十和田.
  • Invited
• [Presentation] 鶏における黄色ブドウ球菌の保菌状況の調査と病原遺伝子の解析 (2019)
  • Author(s): 小野久弥，木村珠子, 岡本旺久, 渡邊真弥, 鈴木康規，崔 龍洙, 岡村雅史，胡 東良
  • Organizer: 第64回日本ブドウ球菌研究会, 長崎.
• [Presentation] 肥満細胞におけるブドウ球菌エンテロトキシンA受容体の検索 (2019)
  • Author(s): 永田真理菜,小野久弥,岡村雅史,中根明夫,胡 東良
  • Organizer: 第162回日本獣医学会学術集会, つくば.
• [Presentation] ブドウ球菌エンテロトキシンCはマクロファージ内での黄色ブドウ球菌の生存を増強させる (2019)
  • Author(s): 八坂嘉希子,小野久弥,松永 萌,小林美樹,岡村雅史,中根明夫,胡 東良
  • Organizer: 第162回日本獣医学会学術集会, つくば.
• [Presentation] 黄色ブドウ球菌感染が炎症性腸疾患に与える影響の解析 (2019)
  • Author(s): 茂木遼介,小野久弥,岡村雅史,中根明夫,胡 東良
  • Organizer: 第162回日本獣医学会学術集会, つくば.
• [Presentation] 食鳥処理場に搬入された鶏におけるブドウ球菌の保菌状況と病原遺伝子の解析 (2019)
  • Author(s): 小野久弥，木村珠子, 岡本旺久, 鈴木康規，岡村雅史, 胡 東良
  • Organizer: 第40回日本食品微生物学会学術総会, 船堀
• [Presentation] Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A (SEA) evokes vomiting reflex in common marmoset (2019)
  • Author(s): Ono, H., Hirose, S., Narita, K., Sugiyama, M., Asano, K., Hu, D.-L., Nakane, A.
  • Organizer: 第42回日本分子生物学学会年会, 福岡.
• [Presentation] ブドウ球菌エンテロトキシンの新たな生物活性-細胞増殖活性の解明. (2018)
  • Author(s): 松永 萌、小野 久弥、小林 美樹、岡村 雅史、中根 明夫、胡 東良.
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] ブドウ球菌エンテロトキシンは鶏の皮膚組織の炎症反応を惹起する (2018)
  • Author(s): 森口 優佳、小野 久弥、小林 美樹、岡本 旺久、岡村 雅史、中根 明夫、胡 東良
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] 鶏における黄色ブドウ球菌の保菌状況の調査と病原遺伝子の解析 (2018)
  • Author(s): 木村 珠子、小野 久弥、岡村 雅史、津曲 歩径、松永 萌、森口 優佳、中根 明夫、胡 東良
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] The prevalence and pathogenic factors of Staphylococcus aureus from chickens in Japan (2018)
  • Author(s): Ono, HJ., Kimura, T., Okamura, M. and Hu D.-L.
  • Organizer: 18th International Symposium on Staphylococci and Staphylococcal Infections ( ISSSI 2018)
  • Int'l Joint Research
• [Presentation] PREVALENCE AND CHARACTERIZATION OF STAPHYLOCOCCUS AUREUS ISOLATED FROM CAMEL AND COW MILK IN SINKIANG, CHINA (2018)
  • Author(s): Fang, R., Jiang, J., Chen, T., Jiang, B., Xie, J., Liang, W., Yang, Z., Lin, L., Peng, Y., Hu, D.-L., Wang, H.
  • Organizer: 18th International Symposium on Staphylococci and Staphylococcal Infections ( ISSSI 2018)
  • Int'l Joint Research
• [Presentation] Emetic activity of recently identified staphylococcal enterotoxins in cynomolgus monkey and house musk shrew. (2017)
  • Author(s): Ono, H.K., Omoe, K., Hirose, S., Nakane, A. and Hu, D-L.
  • Organizer: International Union of Microbiological Societies (IUMS 2017).
  • Int'l Joint Research
• [Presentation] Staphylococcal enterotoxin Q, a nonclassical enterotoxin, is a high risk toxin in food poisoning. (2017)
  • Author(s): Hu, D-L., Ono, H.K., Isayama, S., Okada, R., Okamura, M., Lei, L., Liu, Z., Liu, M., Cui, J. and Nakane, A.
  • Organizer: International Union of Microbiological Societies (IUMS 2017).
  • Int'l Joint Research
• [Presentation] ブドウ球菌感染免疫機構及びワクチンの開発研究． (2017)
  • Author(s): 胡 東良
  • Organizer: 中国第5届東北三省一区免疫学会学術会議.
  • Invited
• [Presentation] 新型ブドウ球菌エンテロトキシンの発見と食中毒へのリスク. (2017)
  • Author(s): 小野久弥，中根明夫，胡 東良.
  • Organizer: 第62回日本ブドウ球菌研究会.
  • Invited
• [Presentation] ブドウ球菌エンテロトキシンによる細胞空胞形成機序の解明. (2017)
  • Author(s): 小林美樹，小野久弥，河合美帆，稲野辺悠，岡村雅史，中根明夫，胡 東良.
  • Organizer: 第160回日本獣医学会学術集会.
• [Presentation] ブドウ球菌エンテロトキシン様毒素SElJの高感度検出系の確立. (2017)
  • Author(s): 蜂谷信昭，小野久弥，岡村雅史，中根明夫，胡 東良.
  • Organizer: 第160回日本獣医学会学術集会.
• [Presentation] 動物源性食品の安全危害及びその制御. (2017)
  • Author(s): 胡 東良
  • Organizer: 中国・西南大学シンポジウム
  • Invited
• [Presentation] スンクス嘔吐モデルを用いたブドウ球菌食中毒メカニズムの解明． (2017)
  • Author(s): 胡 東良，小野久弥，岡村雅史．
  • Organizer: 第11回日本スンクス研究会・第122回日本解剖学会
  • Invited
• [Presentation] 黄色ブドウ球菌の毒素性ショック症候群毒素の産生と増殖への関与． (2016)
  • Author(s): 菊池菜央，岡村雅史，小野久弥，稲野辺悠，大橋真奈，中根明夫，胡 東良．
  • Organizer: 第159回日本獣医学会学術集会．
  • Place of Presentation: 日本大学（神奈川県藤沢市）
  • Year and Date: 2016-09-06
• [Presentation] ブドウ球菌エンテロトキシンの新たな生物活性：細胞空胞化作用． (2016)
  • Author(s): 稲野辺悠，岡村雅史，小野久弥，菊池菜央，河合美帆，中根明夫，胡 東良．
  • Organizer: 第159回日本獣医学会学術集会．
  • Place of Presentation: 日本大学（神奈川県藤沢市）
  • Year and Date: 2016-09-06
• [Presentation] Update on the molecular diversity and multifunctionality of staphylococcal enterotoxin superfamily. (2016)
  • Author(s): Hu, D.-L.
  • Organizer: International Symposium on Staphylococci and Staphylococcal Infection (ISSSI).
  • Place of Presentation: Nine Tree Convention Center, Seoul, South Korea
  • Year and Date: 2016-08-30
  • Int'l Joint Research / Invited
• [Presentation] Goblet cells are involved in translocation of staphylococcal enterotoxin A in the intestinal tissue. (2016)
  • Author(s): Hirose, S., Ono, H.K., Omoe, K., Hu, D.-L., Asano, K., Yamamoto, Y. and Nakane, A.
  • Organizer: International Symposium on Staphylococci and Staphylococcal Infection (ISSSI).
  • Place of Presentation: Nine Tree Convention Center, Seoul, South Korea
  • Year and Date: 2016-08-30
  • Invited
• [Presentation] ブドウ球菌エンテロトキシン様毒素 SElJ の発現・精製と生物活性の解析． (2016)
  • Author(s): 小野久弥，鈴木康規，廣瀬昌平，胡 東良，中根明夫．
  • Organizer: 日本細菌学会東北支部総会．
  • Place of Presentation: 北里大学（青森県十和田市）
  • Year and Date: 2016-08-18
• [Book] 獣医微生物学 第４版 (2018)
  • Author(s): 胡 東良 （関崎勉、遠矢幸伸、福士秀人、堀本泰介、村瀬敏之編集）
  • Total Pages: 6
  • Publisher: 文英堂出版
• [Book] Staphylococcus aureus (2017)
  • Author(s): HU, D.-L., et al.
  • Total Pages: 17
  • Publisher: Elsevier Academic Press
  • ISBN: 9780128096710