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Biofilm promoting factors for aspergillus in human serum and azole resistance of the fungus

Research Project

Project/Area Number 18K07103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionChiba University

Principal Investigator

KAMEI KATSUHIKO  千葉大学, 真菌医学研究センター, 教授 (10214545)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsaspergillus / biofilm / azole resistance / fungus ball / serum component / アスペルギルス / バイオフィルム産生 / 薬剤耐性 / 血清 / 病原真菌 / アスペルギルス症 / 耐性化 / バイオフィルム / Aspergillus / drug resistance / fetuin A
Outline of Final Research Achievements

We searched for biofilm formation-promoting factors of Aspergillus fumigatus in human serum. First, a simple biofilm formation assay was newly established. Then using this method, we analyzed human serum to find biofilm formation promoting factors. We found potent activity in the fraction below 10 kDa, and this activity was as intense as that of fetuin A. We also found that high-density lipoprotein (HDL) complexes in serum strongly inhibited the growth of A. fumigatus.
In the search for biofilm-forming gene profile in A. fumigatus, we collected fungi obtained from the same patients over time and examined their drug susceptibility, biofilm-forming ability, and genetic mutations. As a result, we identified gene mutations with the potentials to significantly suppress biofilm production.

Academic Significance and Societal Importance of the Research Achievements

本研究により、アスペルギルスが感染時に、複数のヒト血清成分を自らのbiofilm形成に利用していることが明らかになったが、同時に、全く予想していなかった一部の血清成分はアスペルギルスに対して抑制的に作用していることも見いだされた.また、比較ゲノム法により、biofilm形成促進に関与する遺伝子候補が確認された。
今後、これらの血清中の有効成分の解析やbiofilm形成遺伝子の解析により、難治化及び耐性化の原因であるbiofilm形成の抑制を標的とした全く新しい治療戦略への道が示された.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (34 results)

All 2020 2019 2018

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 8 results) Presentation (21 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results)

  • [Journal Article] Disruption of Aspergillus fumigatus biofilm by Streptococcus pneumoniae: Mycelial fragmentation by hydrogen peroxide2020

    • Author(s)
      Iwahashi Jun、Kamei Katsuhiko、Watanabe Hiroshi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Issue: 8 Pages: 831-837

    • DOI

      10.1016/j.jiac.2020.03.015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Streptococcus pneumoniaeが産生する過酸化水素によるAspergillus fumigatus菌糸体分断2020

    • Author(s)
      岩橋潤,渡邊浩,亀井克彦
    • Journal Title

      BACTERIAL ADHERENCE & BIOFILM

      Volume: 33 Pages: 33-36

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of Aspergillus fumigatus biofilm by Streptococcus pneumoniae: mycelial fragmentation by hydrogen peroxide2020

    • Author(s)
      Jun Iwahashi、Katsuhiko Kamei、Hiroshi Watanabe
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Simple Method To Detect Point Mutations in Aspergillus fumigatus cyp51A Gene Using a Surveyor Nuclease Assay2020

    • Author(s)
      Arai Teppei、Majima Hidetaka、Watanabe Akira、Kamei Katsuhiko
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 64 Issue: 4

    • DOI

      10.1128/aac.02271-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fatal invasive pulmonary aspergillosis caused by voriconazole-resistant Aspergillus tubingensis in a patient with solid tumor2020

    • Author(s)
      Harada Sohei、Ohkushi Daisuke、Nakano Kenji、Mitani Hiroki、Yamamoto Yutaka、Kamei Katsuhiko、Hayama Brian
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Issue: 3 Pages: 301-304

    • DOI

      10.1016/j.jiac.2019.10.022

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biosynthesis of β-(1→5)-Galactofuranosyl Chains of Fungal-Type and O-Mannose-Type Galactomannans Within the Invasive Pathogen Aspergillus Fumigatus.2020

    • Author(s)
      Chihara Y, Tanaka Y, Izumi M, Hagiwara D, Watanabe A, Takegawa K, Kamei K, Shibata N, Ohta K, Oka T.
    • Journal Title

      mSphere

      Volume: 5 Issue: 1

    • DOI

      10.1128/msphere.00770-19

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Substitutions at 98th, 121st, and 289th Amino Acid Residues in Cyp51A using Cycling Probes2020

    • Author(s)
      Toyotome Takahito、Arai Teppei、 Watanabe Akira、 Kamei Katsuhiko
    • Journal Title

      Medical Mycology Journal

      Volume: 61 Issue: 1 Pages: 7-10

    • DOI

      10.3314/mmj.19-00014

    • NAID

      130007803814

    • ISSN
      2185-6486, 2186-165X
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Species identification, antifungal susceptibility, and clinical feature association of Aspergillus section Nigri isolates from the lower respiratory tract2019

    • Author(s)
      Takeda Keita、Suzuki Junko、Watanabe Akira、Matsuki Mei、Higa Katsuyuki、Inoue Eri、Akashi Shunsuke、Shimada Masahiro、Kawashima Masahiro、Ohshima Nobuharu、Fukami Takeshi、Masuda Kimihiko、Yamane Akira、Tamura Atsuhisa、Nagai Hideaki、Matsui Hirotoshi、Tohma Shigeto、Kamei Katsuhiko
    • Journal Title

      Medical Mycology

      Volume: 58 Issue: 3 Pages: 310-314

    • DOI

      10.1093/mmy/myz072

    • NAID

      120006988242

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative genome analysis of Aspergillus flavus clinically isolated in Japan.2019

    • Author(s)
      Toyotome T, Hamada S, Yamaguchi S, Takahashi H, Kondoh D, Takino M, Kanesaki Y, Kamei K.
    • Journal Title

      DNA Research

      Volume: 26 Issue: 1 Pages: 95-103

    • DOI

      10.1093/dnares/dsy041

    • NAID

      120006603073

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aspergillus fumigatus adhesion factors in dormant conidia revealed through comparative phenotypic and transcriptomic analyses2018

    • Author(s)
      Takahashi-Nakaguchi A, Sakai K, Takahashi H, Hagiwara D, Toyotome T, Chibana H, Watanabe A, Yaguchi T, Yamaguchi M, Kamei K, Gonoi T
    • Journal Title

      Cell Microbiol

      Volume: 20 Issue: 3 Pages: e12802-e12802

    • DOI

      10.1111/cmi.12802

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A simple method to detect the tandem repeat of the cyp51A promoter in azole-resistant strains of Aspergillus fumigatus2018

    • Author(s)
      Toyotome T, Hagiwara D, Watanabe A, Kamei K
    • Journal Title

      Med Mycol

      Volume: 印刷中 Pages: 1042-1044

    • DOI

      10.1093/mmy/myx149

    • NAID

      120006540777

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-cyp51A Azole-Resistant Aspergillus fumigatus Isolates with Mutation in HMG-CoA Reductase2018

    • Author(s)
      Hagiwara D, Arai T, Takahashi H, Kusuya Y, Watanabe A, Kamei K
    • Journal Title

      Emerg Infect Dis

      Volume: 24 Issue: 10 Pages: 1889-1897

    • DOI

      10.3201/eid2410.180730

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heterogeneity in Pathogenicity-related Properties and Stress Tolerance in <i>Aspergillus fumigatus</i> Clinical Isolates2018

    • Author(s)
      Hagiwara D, Takahashi H, Takagi H, Watanabe A, Kamei K
    • Journal Title

      Medical Mycology Journal

      Volume: 59 Issue: 4 Pages: E63-E70

    • DOI

      10.3314/mmj.18-00007

    • NAID

      130007538275

    • ISSN
      2185-6486, 2186-165X
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Aspergillus fumigatus で見つかった Cyp51A と Hmg1 の変異によるマルチアゾール耐性株2020

    • Author(s)
      新居鉄平,梅山隆,犬飼達也,渡辺哲,宮﨑義継,亀井克彦
    • Organizer
      第64回日本医真菌学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Aspergillus fumigatus 感性株における cyp51A 遺伝子多型の地域差に関する検討2020

    • Author(s)
      馬嶋秀考,新居鉄平,渡辺哲,宮崎泰成,亀井克彦
    • Organizer
      第64回日本医真菌学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Aspergillus fumigatus のアゾール耐性に関わる新規因子について2020

    • Author(s)
      新居鉄平,高橋弘喜,楠屋陽子,渡辺哲,亀井克彦
    • Organizer
      第64回日本医真菌学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マルチアゾール耐性Aspergillus fumigatusで確認された変異INSIGについて2020

    • Author(s)
      新居鉄平,髙橋弘喜,楠屋陽子,渡辺哲,亀井克彦
    • Organizer
      真菌症フォーラム2020学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] D430G mutation of CYP51A in Aspergillus fumigatus causes azole-resistance2020

    • Author(s)
      Majima Hidetaka, Arai Teppei, Watanabe Akira, Kamei Katsuhiko
    • Organizer
      9th Advances Against Aspergillosis and Mucormycosis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hmg1 mutation conferring multi-azole resistance in Aspergillus fumigatus2020

    • Author(s)
      Arai Teppei, Umeyama Takashi, Inukai Tatsuya, Watanabe Akira, Miyazaki Yoshitsugu, Kamei Katsuhiko
    • Organizer
      9th Advances Against Aspergillosis and Mucormycosis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of cyp51A polymorphisms of Aspergillus fumigatus in Japan2020

    • Author(s)
      Majima Hidetaka, Arai Teppei, Watanabe Akira, Yaguchi Takashi, Miyazaki Yoshitsugu, Kamei Katsuhiko
    • Organizer
      9th Advances Against Aspergillosis and Mucormycosis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome Wide Association Study (GWAS) for antifungal sensitivity in the 84 opportunistic pathogen Aspergillus fumigatus2020

    • Author(s)
      Zhao Shu, Fortwendel Jarrod R, Watanabe Akira, Gibbons John G
    • Organizer
      9th Advances Against Aspergillosis and Mucormycosis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 下気道検体でのAspergillus Section Nigriの細菌学的・臨床的特徴2019

    • Author(s)
      武田啓太,鈴木純子,渡辺哲,平野悠太,比嘉克行,池田みき,伊藤修士,日下圭,成本治,山根章,永井英明,松井弘稔,亀井克彦
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 当院で慢性肺アスペルギルス症より分離されたA. fumigatusのアゾール感受性の現況2019

    • Author(s)
      魲稔隆,大西涼子,加藤達男,村上啓雄,渡辺哲,亀井克彦
    • Organizer
      第93回日本感染症学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 同一患者から単離された遺伝背景の異なるAspergillus fumigatusについて2019

    • Author(s)
      新居鉄平,馬嶋秀考,鎗田響子,渡辺哲,亀井克彦
    • Organizer
      第40回関東医真菌懇話会
    • Related Report
      2019 Research-status Report
  • [Presentation] ゲノム比較解析によるnon-cyp51Aアゾール耐性Aspergillus fumigatusにおける新規耐性因子の探索2019

    • Author(s)
      新居鉄平,萩原大祐,高橋弘喜,楠屋陽子,渡辺哲,亀井克彦
    • Organizer
      真菌症フォーラム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Aspergillus. fumigatus環境株における遺伝子多型とアゾール感受性2019

    • Author(s)
      馬嶋秀考,新居鉄平,渡辺哲,宮崎泰成,亀井克彦
    • Organizer
      真菌症フォーラム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] non-Cyp51A型アゾール耐性HMG1変異のAspergillus fumigatusにおける直接検証:新技術CRISPR/Cas9ゲノム編集の導入2019

    • Author(s)
      梅山隆,新居鉄平,渡辺哲,犬飼達也,亀井克彦,宮﨑義継
    • Organizer
      真菌症フォーラム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Aspergillus fumigatus 臨床感性株と環境株における遺伝子多型2019

    • Author(s)
      馬嶋秀考,新居鉄平,渡邉哲,宮崎泰成,亀井克彦
    • Organizer
      第63回日本医真菌学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Aspergillus species 臨床分離での形態学的診断と遺伝子学的診断の比較2019

    • Author(s)
      武田啓太,鈴木純子,渡邉哲,永井英明,松井弘稔,亀井克彦
    • Organizer
      第63回日本医真菌学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] HMG-CoA reductase に変異を有するnon-cyp51Aアゾール耐性Aspergillus fumigatus2019

    • Author(s)
      新居鉄平,萩原太祐,高橋弘喜,楠屋陽子,渡邉哲,亀井克彦
    • Organizer
      第63回日本医真菌学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 真菌症の現状とその診断ツール2019

    • Author(s)
      亀井克彦
    • Organizer
      第3回質量分析により変貌する臨床検査の最前線
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 深在性真菌症における診断と治療のpitfalls2019

    • Author(s)
      亀井克彦
    • Organizer
      第18回関東深在性真菌症研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Aspergillus fumigatus strains isolated from a single sputum of a chronic aspergillosis patient showed various susceptibilities to azoles2018

    • Author(s)
      Rie Anazawa, Katsuhiko Kamei, Daisuke Hagiwara, Kyoko Yarita, Misako Ohkusu, Shota Murata, Akira Watanabe, Koichiro Tatsumi
    • Organizer
      Global Network Forum on Infection and Immunity 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] フェチュインのシアル酸が Aspergillus fumigatus の生育及び菌糸への結合に及ぼす影響2018

    • Author(s)
      藤村佳絵、亀井克彦、豊留孝仁
    • Organizer
      第62回日本医真菌学会総会・学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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