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Investigation of host-bacterial interactions in staphylococcal cutaneous infection and development of its prevention strategies

Research Project

Project/Area Number 17H03922
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Veterinary medical science
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

NISHIFUJI Koji  東京農工大学, (連合)農学研究科(研究院), 准教授 (20365422)

Co-Investigator(Kenkyū-buntansha) 秋山 真志  名古屋大学, 医学系研究科, 教授 (60222551)
高島 康弘  岐阜大学, 応用生物科学部, 准教授 (20333552)
菅井 基行  広島大学, 医歯薬保健学研究科(歯), 教授 (10201568)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords皮膚 / ブドウ球菌 / 好中球 / 膿皮症 / 表皮剥脱毒素 / スフィンゴ脂質 / 病原因子 / 角質層 / 表皮バリア / 周辺帯 / 皮膚感染症 / 角層
Outline of Final Research Achievements

In this study, we aimed to investigate how staphylococci invade to the epidermis through the strartum corneum of barrier-disrupted skin.
1. A conditional knockout mouse line in which sptlc2 gene that is involved in production of sphingolipids is deleted in the stratified squamous epithelia. We revealed that sptlc2 gene is effectively deleted in the mouse line 2-3 weeks after induction of gene-recombination by tamoxifen.
2. We also aimed to identify cell-wall molecules or exotoxins involved in intra-epidermal invasion of staphylococcus aureus. We revealed that mutant S. aureus RN4220 strain in which either protein A or basic phospolipids are deleted tended to decrease neutrophilic migration to the epidermis than wild-type RN4220.

Academic Significance and Societal Importance of the Research Achievements

本研究では、皮膚バリア機能に関連するスフィンゴ脂質の合成酵素を重層扁平上皮特異的に欠損したマウスを作出した。イヌ膿皮症やイヌアトピー性皮膚炎では、角質層においてスフィンゴ脂質の発現量が低下していることが知られている。したがってこのマウスは、イヌの再発性膿皮症やアトピー性皮膚炎における病態学的発症機序を解明する目的で有用になると考えられた。
また本研究では、黄色ブドウ球菌が有する特定の細胞壁分子が好中球の表皮内浸潤に影響する可能性を示唆した。黄色ブドウ球菌は好中球により形成された表皮細胞間を通過することから、本研究の成果は黄色ブドウ球菌の経皮侵入機構の一部を説明できるものと考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (29 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (5 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] SLTO INRA(フランス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Federal University of Minas Gerais(ブラジル)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] IBILCE/UNESP(ブラジル)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] INRA(フランス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Universidade Estadual Paulista/Federal University of Minas Gerais(ブラジル)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Development of an in Vitro Submerged Culture System to Synthesize Epidermal Ceramides in Canine Keratinocytes2020

    • Author(s)
      Yoon JS, Nishifuji K, Iwasaki T.
    • Journal Title

      Research in Veterinary Science

      Volume: 130 Pages: 48-51

    • DOI

      10.1016/j.rvsc.2020.02.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exfoliative Toxin E, a New Staphylococcus Aureus Virulence Factor With Host-Specific Activity2019

    • Author(s)
      Imanishi I, Nicolas A, Caetano AB, Castro TLP, Tartaglia NR, Mariutti R, Guedon E, Even S, Berkova N, Arni RK, Seyffert N, Azevedo V, Nishifuji K, Le Loir Y
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1

    • DOI

      10.1038/s41598-019-52777-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic Potential of an Endolysin Derived from Kayvirus S25-3 for Staphylococcal Impetigo2019

    • Author(s)
      Imanishi Ichiro、Uchiyama Jumpei、Tsukui Toshihiro、Hisatsune Junzo、Ide Kaori、Matsuzaki Shigenobu、Sugai Motoyuki、Nishifuji Koji
    • Journal Title

      Viruses

      Volume: 11 Issue: 9 Pages: 769-769

    • DOI

      10.3390/v11090769

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Progenitor cells expressing nestin, a neural crest stem cell marker, differentiate into outer root sheath keratinocytes2019

    • Author(s)
      Onishi S, Baba Y, Yokoi F, Ide K, Ohyama M, Nishifuji K
    • Journal Title

      Veterinary Dermatology

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] First Identification of a single amino acid change in the spike protein region of feline coronavirus detected from a coronavirus-associated cutaneous nodule in a cat2018

    • Author(s)
      Osumi T, Mitsui I, Leutenegger CM, Okabe R, Ide K, Nishifuji K
    • Journal Title

      Journal of Feline Medicine and Surgery Open Reports

      Volume: 4 Issue: 2

    • DOI

      10.1177/2055116918801385

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Collagen-enriched serpiginous skin lesion in a cat resembling linear form of localized scleroderma in humans2018

    • Author(s)
      Osumi T, Mitsui I, Morita A, Iyori K, Nishifuji K
    • Journal Title

      The Journal of Veterinary Medical Science

      Volume: 80 Pages: 1077-1079

    • NAID

      130007404168

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Piperacillin and ceftazidime produce the strongest synergistic phage-antibiotic effect in Pseudomonas aeruginosa.2018

    • Author(s)
      Uchiyama J, Shigehisa R, Nasukawa T, Mizukami K, Takemura-Uchiyama I, Ujihara T, Murakami H, Imanishi I, Nishifuji K, Sakaguchi M, Matsuzaki S.
    • Journal Title

      Archives of Virology

      Volume: in press Issue: 7 Pages: 1-8

    • DOI

      10.1007/s00705-018-3811-0

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Langrhans cells prevent autoimmunity via expansion of keratinocyte antigen-specific regulatory T cells2017

    • Author(s)
      Kitashima DY, Kobayashi T, Woodring T, Idouchi K, Doebei T, Voisin B, Adachi T, Takahashi H, Nishifuji K, Kaplan DH, Clausen BE, Amagai M, Nagao K
    • Journal Title

      EBioMedicine

      Volume: 27 Pages: 293-303

    • DOI

      10.1016/j.ebiom.2017.12.022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 哺乳動物の細胞接着を壊すブドウ球菌の外毒素:表皮剥脱毒素2020

    • Author(s)
      西藤公司
    • Organizer
      第23回日本獣医皮膚科学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] イヌ表在性膿皮症症例の膿疱より分離されたブドウ球菌の遺伝子学的相同性2019

    • Author(s)
      大隅尊史、篠宮佑季、今西市朗、井手香織、西藤公司
    • Organizer
      第64回日本ブドウ球菌研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Kayvirus型endolysinエンドリシンの溶菌活性と膿痂疹モデルマウスに対する治療効果の解析2019

    • Author(s)
      今西市朗、内山淳平、津久井利広、久恒順三、井手香織、松崎茂展、菅井基行、西藤公司
    • Organizer
      MRSAフォーラム2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Canine atopic dermatitis - complex pathogenesis2019

    • Author(s)
      Nishifuji K
    • Organizer
      6th Asian Meetings of Animal Medicine Specialties
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cutaneous barrier function and ecosystem - Part II: Cutaneous ecosystem, immunity and diseases2018

    • Author(s)
      Nishifuji K
    • Organizer
      31th North American Veterinary Dermatology Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cutaneous barrier function and ecosystem - Part I: Barrier abnormalities and diseases2018

    • Author(s)
      Nishifuji K
    • Organizer
      31th North American Veterinary Dermatology Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] バクテリオファージS25-3に由来する組換えendolysinの皮膚常在菌に対する溶菌特異性の解析2018

    • Author(s)
      今西市朗,内山淳平,井手香織,菅井基行,西藤公司
    • Organizer
      第7回ファージ研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Recombinant endolysin of bacteriophage S25-3 preferentially targets Staphylococcus aureus and prevents pustule formation in a mouse model of bullous impetigo2018

    • Author(s)
      Imanishi I, Uchiyama J, Mizutani A, Ide K, Sugai M, Nishifuji K
    • Organizer
      第63回日本ブドウ球菌研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Staphylococcal exfoliative toxin -A dark side of the Force2018

    • Author(s)
      Nishifuji K
    • Organizer
      MRC-KHIDI workshop
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] バクテリオファージS25-3に由来するendolysin組換え酵素は膿痂疹モデルマウスにおける膿疱形成を抑制する2017

    • Author(s)
      今西市朗,内山淳平,水谷歩実,井手香織,西藤公司
    • Organizer
      MRSAフォーラム2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Intra-epidermal neutrophilic migration is crucial for invasion of Staphylococcus aureus to the living epidermis in a mouse model of bullous impetigo2017

    • Author(s)
      Imanishi I, Hattori S, Hisatsune J, Ide K, Uchiyama J, Sugai M, Nishifuji K
    • Organizer
      International Union of Microbiological Societies 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Canine pyoderma; from laboratory to clinic2017

    • Author(s)
      Nishifuji K
    • Organizer
      5th Asian Meetings of Animal Medicine Specialties
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Immunology and Microbiology "The Rise of Virulence and Antibiotic Resistance in Staphylococus aureus"2017

    • Author(s)
      Mariutti RB, Tartaglia NR, Seyffert N, de Castro TL, Arni RK, Azevedo VA, Loir YL, Nishifuji K
    • Total Pages
      206
    • Publisher
      Intech
    • ISBN
      9789535129844
    • Related Report
      2017 Annual Research Report
  • [Remarks] 西藤 公司

    • URL

      https://kenkyu-web.tuat.ac.jp/Profiles/15/0001474/profile.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京農工大学 農学研究院 動物生命科学部門 准教授 西藤公司

    • URL

      http://kenkyu-web.tuat.ac.jp/Profiles/15/0001474/profile.html?lang=ja&#ronbun

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • URL

      http://kenkyu-web.tuat.ac.jp/Profiles/15/0001474/profile.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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