Pathogenic strategy of staphylococcal superantigens in microenvironment of tissues and organs

• Project/Area Number: 16H05185
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Hirosaki University
• Principal Investigator: Nakane Akio 弘前大学, 医学研究科, 特任教授 (30164239)
• Research Collaborator: Asano Krisana ; Ono Hisaya ; Narita Kouji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 黄色ブドウ球菌 / TSST-1 / 毒素性ショック症候群 / オートファジー / 経膣感染 / 子宮感染 / 皮膚感染

Outline of Final Research Achievements

We investigated the role of toxic shock syndrome toxin-1 (TSST-1), a superantigenic toxin, produced by Staphylococcus aureus during infection.
(1) We identified a septin family molecule as the TSST-1-binding protein. It was suggested that that TSST-1 suppresses autophagy by interacting with the septin family molecule. We are now investigating the role of the septin family molecule in S. aureus infection. (2) We established the staphylococcal cervicovaginal infection mouse as a model of “so-called Tampon disease”. It was suggested that TSST-1, which is produced in uterine, translocates to bloodstream and onsets systemic inflammation like toxic shock syndrome, although S. aureus remains in uterine.

Academic Significance and Societal Importance of the Research Achievements

細菌感染症に対し抗菌薬が大いに貢献してきた一方,薬剤耐性菌が大きな脅威となり，2050年には薬剤耐性菌感染症による死亡者ががんによる死亡者を上まると予測されている。多剤耐性黄色ブドウ球菌であるMRSAはその代表格である。黄色ブドウ球菌の病原性は極端に高いわけではなく，むしろ私たちと共存すべく進化している。従って，MRSA感染症の制御には黄色ブドウ球菌と私たちの免疫系との攻防・協調メカニズムを知ることが必須である。私たちは，黄色ブドウ球菌の代表的な病原因子であるTSST-1を基点に，黄色ブドウ球菌と私たちの相互作用の全容を明らかにすべく研究を続けている。本研究は，その一端を解明したものである。

Research Products

• [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] Chronic irradiation with 222-nm UVC light induces neither DNA damage nor epidermal lesions in mouse skin, even at high doses (2018)
  • Author(s): Narita K, Asano K, Morimoto Y, Igarashi T, Nakane A
  • Journal Title: PLoS One Volume: 13 Issue: 7 Pages: e0201259-e0201259
  • DOI: 10.1371/journal.pone.0201259
  • Peer Reviewed / Open Access
• [Journal Article] Salmon cartilage proteoglycan attenuates allergic responses in mouse model of papain-induced respiratory inflammation (2018)
  • Author(s): Ono HK, Yoshimura S, Hirose S, Narita K, Tsuboi M, Asano K, Nakane A
  • Journal Title: Molecular Medicine Reports Volume: 18 Pages: 4058-4064
  • DOI: 10.3892/mmr.2018.9364
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of toxic shock syndrome toxin-1 to systemic inflammation investigated by a mouse model of cervicovaginal infection with Staphylococcus aureus (2018)
  • Author(s): Asano K, Narita K, Hirose S, Nakane A
  • Journal Title: Medical Microbiology and Immunology Volume: 207 Issue: 5-6 Pages: 297-306
  • DOI: 10.1007/s00430-018-0551-4
  • Peer Reviewed
• [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] Vitamin A deficiency impairs resistance to Listeria monocytogenes infection through excessive apoptosis of macrophages (2018)
  • Author(s): Tanaka N, Hiraga H, Sakuraba H, Murai Y, Maeda T, Watanabe R, Ota S, Akemoto Y, Hasui K, Yoshida S, Asano K, Nakane A, Fukuda S
  • Journal Title: Hirosaki Medical Journal Volume: 69 Pages: 163-171
  • Peer Reviewed
• [Journal Article] Oral administration of salmon cartilage proteoglycan extends the survival of allografts in mice (2018)
  • Author(s): Asano K, Takahashi E, Yoshimura S, Nakane A
  • Journal Title: Biomedical Reports Volume: 8 Pages: 37-40
  • DOI: 10.3892/br.2017.1011
  • Peer Reviewed / Open Access
• [Journal Article] Disinfection and healing effects of 222-nm UVC light on methicillin-resistant Staphylococcus aureus infection in mouse wounds (2018)
  • Author(s): Narita K, Asano K, Morimoto Y, Igarashi T, Hamblin MR, Dai T, Nakane A
  • Journal Title: Journal of Photochemistry and Photobiology B Biology Volume: 178 Pages: 10-18
  • DOI: 10.1016/j.jphotobiol.2017.10.030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Salmon cartilage proteoglycan promotes the healing process of Staphylococcus aureus-infected wound (2018)
  • Author(s): Hirose S, Narita K, Asano K, Nakane A
  • Journal Title: Heliyon Volume: 4 Issue: 3 Pages: e00587-e00587
  • DOI: 10.1016/j.heliyon.2018.e00587
  • Peer Reviewed / Open Access
• [Journal Article] IL-17A plays an important role in protection induced by vaccination with fibronectin-binding domain of fibronectin-binding protein A against Staphylococcus aureus infection (2017)
  • Author(s): Narita K, Asano K, Nakane A
  • Journal Title: Med Microbiol Immunol Volume: 206 Issue: 3 Pages: 225-234
  • DOI: 10.1007/s00430-017-0499-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] Salmon nasal cartilage proteoglycan enhances growth of normal human dermal fibroblast through Erk1/2 phosphorylation (2017)
  • Author(s): Sano M, Shang Y, Nakane A, Saito T
  • Journal Title: Bioscience, Biotechnology and Biochemistry Volume: 81 Issue: 7 Pages: 1369-1378
  • DOI: 10.1080/09168451.2017.1318695
  • Peer Reviewed / Open Access
• [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] Interplay between autophagy and pathogenic bacteria: Toxins secreted by Staphylococcus aureus and their impact on autophagy (2017)
  • Author(s): Asano K, Nakane A.
  • Journal Title: Hirosaki Medical Journal Volume: 67 Pages: 115-128
  • NAID: 130008038297
  • Peer Reviewed
• [Journal Article] Passive immunization with anti-ActA and anti-listeriolysin O antibodies protects against Listeria monocytogenes infection in mice (2016)
  • Author(s): Asano K, Sashinami H, Osanai A, Hirose S, Ono HK, Narita K, Hu DL, Nakane A.
  • Journal Title: Scientific Reports Volume: 6 Pages: 39628-39628
  • Peer Reviewed / Open Access
• [Presentation] Contribution of toxic shock syndrome toxin-1 to tampon-related toxic shock syndrome investigated by a mouse model of cervicovaginal infection (2018)
  • Author(s): Asano K, Nakane A
  • Organizer: 18TH International Sytmposium on Staphylococci and Staphylococcal Infections
  • Int'l Joint Research
• [Presentation] Establishment of a mouse cervicovaginal infection model to investigate the role of toxic shock syndrome toxin-1 on uterine infection of Staphylococcus aureus (2018)
  • Author(s): Asano K, Nakane A
  • Organizer: 第63回日本ブドウ球菌研究会
• [Presentation] マーモセット嘔吐モデルの確立およびブドウ球菌エンテロトキシンの嘔吐発言機序の解明 (2018)
  • 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63回日本ブドウ球菌研究会
• [Presentation] 無毒変異toxic shock syndrome toxin-1ワクチンで誘導されるメモリーTh17細胞のサイトカイン産生の可塑性とワクチン効果に関する検討 (2018)
  • Author(s): 成田浩司、胡 東良、浅野クリスナ、中根明夫
  • Organizer: 第63回日本ブドウ球菌研究会
• [Presentation] ブドウ球菌エンテロトキシンAの腸管吸収上皮細胞への取り込み (2018)
  • Author(s): 廣瀬昌平、小野久弥、浅野クリスナ、中根明夫
  • Organizer: 第63回日本ブドウ球菌研究会
• [Presentation] Systemic distribution of TSST-1 investigated by vaginocervical infection of mouse model (2018)
  • Author(s): Asano K, Nakane A
  • Organizer: 第91回日本細菌学会総会
• [Presentation] 222 nm UVC light elicits sterilizing effect without DNA damage in mouse keratinocytes (2018)
  • Author(s): Narita K, Sasaki M, Morimoto Y, Igarashi T, Nakane A
  • Organizer: 第91回日本細菌学会総会
• [Presentation] Impact of toxic shock syndrome toxin-1 on autophagy and skin infection of Staphylococus aureus (2017)
  • Author(s): Asano K, Nakane A
  • Organizer: The 8th International Symposium on Autophagy
  • Int'l Joint Research
• [Presentation] Effect of toxic shock syndrome toxin-1 on Staphylococcus aureus infections in uterine and skin mouse models (2017)
  • Author(s): Asano K, Nakane A
  • Organizer: IUMS 2017 Singapore International Union of Microbiological Societies
  • Int'l Joint Research
• [Presentation] Novel function of toxic shock syndrome toxin-1 contributes to autophagy and Staphylococcus aureus infection (2017)
  • Author(s): Asano K, Nakane A
  • Organizer: 第62回日本ブドウ球菌研究会
  • Invited
• [Presentation] 無毒変異toxic shock syndrome toxin-1ワクチンによるTh17細胞依存性の黄色ブドウ球菌感染防御効果 (2017)
  • Author(s): 成田浩司、胡 東良、浅野クリスナ、中根明夫
  • Organizer: 第62回日本ブドウ球菌研究会
• [Presentation] サケ鼻軟骨抽出プロテオグリカンは黄色ブドウ球菌感染創の治癒を促進する (2017)
  • Author(s): 廣瀬昌平、浅野クリスナ、中根明夫
  • Organizer: 第62回日本ブドウ球菌研究会
• [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
• [Presentation] Establishment of a mouse uterine infection model of Staphylococcus aureus for studying a role of toxic shock syndrome toxin-1 (2017)
  • Author(s): Asano K, Nakane A
  • Organizer: 第46回日本免疫学会総会
• [Presentation] Role of toxic shock syndrome toxin-1 on cervical and skin infections of Staphylococcus aureus (2017)
  • Author(s): Asano K, Nakane A
  • Organizer: 第90回日本細菌学会総会
• [Presentation] Manipulation of autophagy by toxic shock syndrome toxin 1 contributes to Staphylococcus aureus infection (2016)
  • Author(s): Asano K, Nakane A
  • Organizer: The 13th Korea-Japan International Symposium on Microbiology
  • Int'l Joint Research
• [Presentation] Vaccination with non-toxic mutant toxic shock syndrome toxin-1 elicits IL-17-dependent protection against Staphylococcus aureus infection (2016)
  • Author(s): Narita K, Hu D-L, Asano K, Nakane A
  • Organizer: The 13th Korea-Japan International Symposium on Microbiology
  • Int'l Joint Research
• [Presentation] SEA translocates into intestinal tissue via goblet cells in house musk shrew (Suncs murinus) (2016)
  • Author(s): Hirose S, Ono HK, Omoe K, Hu DL, Asano K, Yamamoto Y, Nakane A
  • Organizer: 17TH International Sytmposium on Staphylococci and Staphylococcal Infections 2016
  • Int'l Joint Research
• [Presentation] Toxic shock syndrome toxin-1 contributes to Staphylococcus aureus infection mediated by autophagy suppression (2016)
  • Author(s): Asano K, Nakane A
  • Organizer: 17TH International Sytmposium on Staphylococci and Staphylococcal Infections 2016
  • Int'l Joint Research
• [Presentation] Vaccination with Staphylococcus aureus fibronection binding domain of Fnbpa induced IL-17A-dependent host defense (2016)
  • Author(s): Narita K, Asano K, Nakane A
  • Organizer: 17TH International Sytmposium on Staphylococci and Staphylococcal Infections 2016
  • Int'l Joint Research
• [Presentation] The emetic activity of staphylococcal enterotoxins, SEK, SEL, SEM, SEN and SEO, in a small emetic animal model, house musk shrew (2016)
  • Author(s): Ono HK, Hirose S, Naito I, Sato’o Y, Asano K, Hu DL, Ome K, Nakane A
  • Organizer: 17TH International Sytmposium on Staphylococci and Staphylococcal Infections 2016
  • Int'l Joint Research
• [Remarks] 感染生体防御学講座 生体高分子健康科学講座
  • URL: http://www.med.hirosaki-u.ac.jp/~mai/
• [Remarks] 感染生体防御学講座
  • URL: http://www.med.hirosaki-u.ac.jp/~mai/