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Molecular characterisation of invasive infection caused by beta haemolytic Streptococci using the organotypic human skin tissue model

Research Project

Project/Area Number 19K08964
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionMeijo University (2021)
Tokyo University of Pharmacy and Life Science (2019-2020)

Principal Investigator

Wajima Takeaki  名城大学, 薬学部, 准教授 (00516669)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsβ溶血性レンサ球菌 / 3次元皮膚組織モデル / SDSE / 侵襲性レンサ球菌感染症 / G群レンサ球菌 / レンサ球菌 / 侵襲性感染症 / 3次元培養 / 皮膚組織モデル
Outline of Research at the Start

Streptococcus dysgalactiae subsp. equisimilis (SDSE) による重症侵襲性感染症の発症メカニズムには不明な点が多い。本菌は、ヒトにのみ感染症を起こすため、実験動物を用いた適切な実験系がないという問題点がある。そこで、本研究は、疫学解析により同定された高病原性クローンを3次元培養したヒト皮膚組織に感染させ、SDSEの侵襲性機構を解析することを目的としている。侵襲性は、形態学的ならびにサイトカイン産生性で評価し、網羅的RNAseq解析により、侵襲性関連因子を探索する。そして、欠損株の作成や臨床分離株のスクリーニングにより、侵襲性感染症関連因子の同定を行う。

Outline of Final Research Achievements

Little is known about the mechanism of the onset of Streptococcus dysgalactiae subsp equisimilis (SDSE) infection. One of the reasons for this is because there is no appropriate infection model. In this study, we tried to construct the infection model using a three-dimensional skin tissue culture system. To make the model more accurate, adipocytes were added in the model. Infection from SDSE isolated from an invasive infection caused destruction of the epithelial layer and tissue injury. In addition, we demonstrated that some of the strains formed a biofilm-like structure on the tissue, which could contribute to differences in antimicrobial susceptibility between in vivo and in vitro environments.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトの培養細胞を用いた3次元皮膚組織モデルを用いて、Streptococcus dysgalactiae subsp equisimilis (SDSE)感染実験系の構築を行った。その結果、本モデルはSDSEによる皮膚障害と組織の損傷を表すことが示された。このモデルを使用すれば、in vitroでSDSEの病態を再現できると考えられ、今後SDSEの詳細な侵襲性メカニズムの解明が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 2 results) Presentation (15 results)

  • [Journal Article] Molecular characterisation of carbapenem- and tigecycline-resistant Klebsiella pneumoniae strains isolated from blood and bile samples2022

    • Author(s)
      Wajima Takeaki、Sugawara Takashi、Umeda Yutaka、Hagimoto Atsuya、Tanaka Emi、Nakaminami Hidemasa
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 28 Issue: 2 Pages: 187-191

    • DOI

      10.1016/j.jiac.2021.10.005

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quinolone Resistance Is Transferred Horizontally via Uptake Signal Sequence Recognition in Haemophilus influenzae2022

    • Author(s)
      Tanaka Emi、Wajima Takeaki、Uchiya Kei-ichi、Nakaminami Hidemasa
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 66 Issue: 2

    • DOI

      10.1128/aac.01967-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-Level Quinolone-Resistant <i>Haemophilus haemolyticus</i> in Pediatric Patient with No History of Quinolone Exposure2022

    • Author(s)
      Tanaka Emi、Hirai Yuji、Wajima Takeaki、Ishida Yu、Kawamura Yoshiaki、Nakaminami Hidemasa
    • Journal Title

      Emerging Infectious Diseases

      Volume: 28 Issue: 1 Pages: 105-111

    • DOI

      10.3201/eid2801.210248

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and characterization of a novel multidrug-resistant streptococcus, Streptococcus toyakuensis sp. nov., from a blood sample2022

    • Author(s)
      Wajima Takeaki、Hagimoto Atsuya、Tanaka Emi、Kawamura Yoshiaki、Nakaminami Hidemasa
    • Journal Title

      Journal of Global Antimicrobial Resistance

      Volume: - Pages: 316-322

    • DOI

      10.1016/j.jgar.2022.04.018

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the Antimicrobial Effects of a Novel Visible Light-driven Photocatalyst <i>in Vitro</i> and in the Environment2021

    • Author(s)
      Wajima Takeaki、Nakaminami Hidemasa、Aoki Sae、Seyama Shoji、Noguchi Norihisa
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 141 Issue: 1 Pages: 135-142

    • DOI

      10.1248/yakushi.20-00171

    • NAID

      130007964827

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2021-01-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of the bactericidal effects of quinolones against low-susceptible Haemophilus influenzae2021

    • Author(s)
      Mizoi Kosei、Wajima Takeaki、Tanaka Emi、Nakaminami Hidemasa、Noguchi Norihisa
    • Journal Title

      Journal of Medical Microbiology

      Volume: 70 Issue: 6

    • DOI

      10.1099/jmm.0.001376

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adjunctive Rifampicin Increases Antibiotic Efficacy in Group A Streptococcal Tissue Infection Models2021

    • Author(s)
      Bergsten H.、Palma Medina L. M.、Morgan M.、Moll K.、Skutlaberg D. H.、Skrede S.、Wajima T.、Svensson M.、Norrby-Teglund A.
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 65 Issue: 11

    • DOI

      10.1128/aac.00658-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan2021

    • Author(s)
      Ubukata Kimiko、Wajima Takeaki、Takata Misako、Murayama Somay Y.、Morozumi Miyuki、Mukae Hiroshi、Ishida Tadashi、Miyairi Isao、Kiyota Hiroshi、Iwata Satoshi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 27 Issue: 2 Pages: 211-217

    • DOI

      10.1016/j.jiac.2020.09.014

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] pspK acquisition contributes to the loss of capsule in pneumococci: molecular characterisation of non-encapsulated pneumococci2020

    • Author(s)
      Wajima Takeaki、Ishikawa Haruna、Matsuzawa Akane Iris、Yamashita Kanae、Suzuki Shiori、Osato Ryuji、Nakaminami Hidemasa、Noguchi Norihisa
    • Journal Title

      Microbes and Infection

      Volume: 22 Issue: 9 Pages: 451-456

    • DOI

      10.1016/j.micinf.2020.05.014

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Whole-genome sequence of Haemophilus influenzae ST422 outbreak clone strain 2018-Y40 with low quinolone susceptibility isolated from a paediatric patient2020

    • Author(s)
      Tanaka Emi、Wajima Takeaki、Nakaminami Hidemasa、Noguchi Norihisa
    • Journal Title

      Journal of Global Antimicrobial Resistance

      Volume: 22 Pages: 759-761

    • DOI

      10.1016/j.jgar.2020.06.024

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] First isolation of an IMP-1 metallo-β-lactamase-producing Kluyvera ascorbata in Japan2020

    • Author(s)
      Wajima Takeaki、Hirai Yuji、Otake Takayuki、Momose Yui、Nakaminami Hidemasa、Noguchi Norihisa
    • Journal Title

      Journal of Global Antimicrobial Resistance

      Volume: 23 Pages: 228-231

    • DOI

      10.1016/j.jgar.2020.09.026

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changes in epidemiologic characteristics and antimicrobial resistance of Streptococcus pyogenes isolated over 10 years from Japanese children with pharyngotonsillitis2020

    • Author(s)
      Ubukata Kimiko、Wajima Takeaki、Morozumi Miyuki、Sakuma Megumi、Tajima Takeshi、Matsubara Keita、Itahashi Koju、Iwata Satoshi
    • Journal Title

      Journal of Medical Microbiology

      Volume: 69 Issue: 3 Pages: 443-450

    • DOI

      10.1099/jmm.0.001158

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] First outbreak of Haemophilus influenzae clone ST422 with low susceptibility to quinolones in paediatric patients in Japan2020

    • Author(s)
      Tanaka Emi、Wajima Takeaki、Hara Naoki、Shirai Atsuko、Shibata Meiwa、Shiro Hiroyuki、Noguchi Norihisa
    • Journal Title

      Journal of Medical Microbiology

      Volume: 69 Issue: 2 Pages: 239-243

    • DOI

      10.1099/jmm.0.001154

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] β-Lactamase-non-producing ampicillin-resistant Haemophilus influenzae is acquiring multidrug resistance2020

    • Author(s)
      Yamada Shogo、Seyama Shoji、Wajima Takeaki、Yuzawa Yuna、Saito Masumi、Tanaka Emi、Noguchi Norihisa
    • Journal Title

      Journal of Infection and Public Health

      Volume: 13 Issue: 4 Pages: 497-501

    • DOI

      10.1016/j.jiph.2019.11.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of the introduction of a 13-valent pneumococcal vaccine on pneumococcal serotypes in non-invasive isolates from 2007 to 2016 at a teaching hospital in Japan2019

    • Author(s)
      Suzuki Shiori、Osato Ryuji、Wajima Takeaki、Hasebe Taisuke、Ishikawa Haruna、Mitsumori Hikari、Nakaminami Hidemasa、Noguchi Norihisa
    • Journal Title

      Journal of Medical Microbiology

      Volume: 68 Issue: 6 Pages: 903-909

    • DOI

      10.1099/jmm.0.000992

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Earlier generation quinolones can be useful in identifying Haemophilus influenzae strains with low susceptibility to quinolone isolated from paediatric patients2019

    • Author(s)
      Tanaka Emi、Wajima Takeaki、Noguchi Norihisa
    • Journal Title

      Journal of Medical Microbiology

      Volume: 68 Issue: 8 Pages: 1227-1232

    • DOI

      10.1099/jmm.0.001027

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Molecular characterisation of high-level quinolone resistant Haemophilus haemolyticus isolated from a paediatric patient with no history of quinolone exposure2022

    • Author(s)
      Emi Tanaka, Takeaki Wajima, Kei-ichi Uchiya, Hidemasa Nakaminami
    • Organizer
      The 21st Asian Conference on Clinicla Pharmacy
    • Related Report
      2021 Annual Research Report
  • [Presentation] キノロン高度耐性Haemophilus haemolyticusのキノロン耐性はH. influenzaeに水平伝播する2022

    • Author(s)
      高林ゆりな、輪島丈明、田中愛海、打矢惠一
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] A群溶血性レンサ球菌のバイオフィルム形成における細胞外マトリックスの影響2022

    • Author(s)
      伊藤侑哉、輪島丈明、田中愛海、打矢惠一
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 首都圏でアウトブレイクしたキノロン低感受性インフルエンザ菌ST422クローンの特徴と抗菌薬治療効果の解析2022

    • Author(s)
      田中愛海、輪島丈明、打矢惠一、中南秀将
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] グラム陽性菌における薬剤耐性の現状2021

    • Author(s)
      輪島丈明
    • Organizer
      第68回日本化学療法学会東日本支部総会 第70回日本感染症学会東日本地方会学術集会 合同学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] カイコを用いた無莢膜型インフルエンザ菌の新規病原因子の探索2021

    • Author(s)
      瀨山翔史、田中愛海、長谷川直樹、 中村茂樹、中南秀将、輪島丈明
    • Organizer
      第68回日本化学療法学会東日本支部総会 第70回日本感染症学会東日本地方会学術集会 合同学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 臨床分離された多剤耐性溶血性Streptococcus属菌の多剤耐性メカニズムの解析2021

    • Author(s)
      萩元 敦也、輪島 丈明、中南 秀将
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 銀翹解毒丸製剤の抗菌活性に寄与する生薬の検討2021

    • Author(s)
      福元 茶穂、輪島 丈明、山田 哲也、中南 秀将
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 皮膚・軟部組織感染症由来β溶血性レンサ球菌の分子疫学的特徴2021

    • Author(s)
      本沢 航晟、輪島 丈明、横山 翔、中南 秀将
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Tannase遺伝子を利用したStreptococcus gallolyticusの特異的検出法2021

    • Author(s)
      矢島 義高、輪島 丈明、中南 秀将、野口 雅久
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] キノロン低感受性インフルエンザ菌のキノロン治療抵抗性と簡易検出法2020

    • Author(s)
      田中 愛海、輪島 丈明、中南 秀将、野口 雅久
    • Organizer
      第32回微生物シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] 肺炎球菌における成人および小児由来株のワクチン導入による莢膜型の変遷2020

    • Author(s)
      山下 香奈枝、輪島 丈明、松澤 茜、野口 雅久
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Enterococcus faecalisは皮膚感染症の起因菌となりうるか2020

    • Author(s)
      横山 翔、輪島 丈明、中南 秀将、野口 雅久
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] A群レンサ球菌のM3タンパクとコラーゲンの結合はバイオフィルム形成を亢進させる2019

    • Author(s)
      輪島 丈明、Helena Bergsten、Ulrich Schwarz-Linek、Mattias Svensson、野口 雅久、Anna Norrby-Teglund
    • Organizer
      第31回微生物シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] USA300 cloneのbiofilmに対する抗MRSA薬の効果2019

    • Author(s)
      金子 寛、中南 秀将、小澤 昂佑、輪島 丈明、野口 雅久
    • Organizer
      MRSAフォーラム2019
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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