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Detection of Rhizopus oryzae specific antigen (RSA) in serum and bronchial alveolar lavage is a potential early diagnostic marker in mucormycosis by R. oryzae

Research Project

Project/Area Number 16K09939
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionOsaka City University

Principal Investigator

KAKEYA Hiroshi  大阪市立大学, 大学院医学研究科, 教授 (40398152)

Co-Investigator(Kenkyū-buntansha) 宮崎 義継  国立感染症研究所, 真菌部, 部長 (00311861)
渋谷 和俊  東邦大学, 医学部, 教授 (20196447)
金子 幸弘  大阪市立大学, 大学院医学研究科, 教授 (90469958)
Research Collaborator NIKI Mamiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsムーコル症 / 早期診断 / 蛋白抗原 / 深在性真菌症 / 特異抗原 / 血清診断 / 新規抗原検査 / Rhizopus oryzae / シグナルシークエンス法 / 抗原血清診断検査 / 抗原検査
Outline of Final Research Achievements

The diagnosis of mucormycosis was made by the identification of organism in the histopathology with culture confirmation. We reported a novel Rhisopus-specific antigen (23kDa, named protein RSA) by screening with a signal sequence trap was detected at significantly higher concentrations in serum and in lung homogenates in the infected mice on day 4. And the results were suggested RSA was a possible diagnostic marker of mucormycosis (Sato K, et al. Medical Mycology, 2017, 55,713-719).
We developed the ELISA Kit using monoclonal antibody for RSA. The mice were injected with cortisone acetate and cyclophosphamide, and R. oryzae was infected intratracheally. The RSA was detected in sera and BAL on day 1, 2, 3, and 4. The concentration of RSA in sera and BAL were significantly higher on day 1 as compared with uninfected mice. And the concentration of RSA in sera was upward trend through day 1 to 4. However, the concentration of RSA in BAL was stable through day 1 to 4.

Academic Significance and Societal Importance of the Research Achievements

白血病疾患等の高度免疫抑制患者に見られる深在性真菌症の中でムーコル症は、早期診断法が未だ開発されておらず、生前診断は困難であることが多い。我々が注目しているA 抗原は分泌蛋白で、感染マウス血清中で検出されることを報告している。今回、モノクローナル抗体の作成に成功し、本抗体を用いたELISA法よる検査にてR. oryzae感染マウスの血清中および肺胞洗浄液中に感染初日から抗原は検出された。これらの結果から、本検査法はR. oryzaeによるムーコル症の早期診断に有用であることが示唆された。さらなる臨床応用にてヒトムーコル症の早期診断につながるものと期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Clinical Characteristics and Low Susceptibility to Daptomycin in <i>Enterococcus faecium</i> Bacteremia2017

    • Author(s)
      Namikawa Hiroki、Yamada Koichi、Shibata Wataru、Fujimoto Hiroki、Takizawa Etsuko、Niki Makoto、Nakaie Kiyotaka、Nakamura Yasutaka、Oinuma Ken-Ichi、Niki Mamiko、Takemoto Yasuhiko、Kaneko Yukihiro、Shuto Taichi、Kakeya Hiroshi
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 243 Issue: 3 Pages: 211-218

    • DOI

      10.1620/tjem.243.211

    • NAID

      130006224988

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a Novel Rhizopus-specific Antigen by Screening with a Signal Sequence Trap and Evaluation as a Possible Diagnostic Marker of Mucormycosis2017

    • Author(s)
      Sato K., Oinuma K., Niki M., Yamagoe S., Miyazaki Y., Asai K., Yamada K., Hirata K., Kaneko Y. and Kakeya H.
    • Journal Title

      Medical Mycology

      Volume: 55 Issue: 7 Pages: 713-719

    • DOI

      10.1093/mmy/myw146

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020099

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] シンポジウム5真菌感染症の検査:培養から抗原検出・遺伝子診断まで「ムーコル症のトピックス」2019

    • Author(s)
      掛屋 弘
    • Organizer
      第30回日本臨床微生物学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ムーコル感染症Up-to-Date2018

    • Author(s)
      掛屋 弘
    • Organizer
      第29回日本臨床微生物学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] シンポジウム 菌種別の最近のトピックスと問題点「ムーコル症の最新のトピックスと今後の課題」2018

    • Author(s)
      掛屋 弘
    • Organizer
      第62回日本医真菌学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 侵襲性肺ムーコル症マウスモデルにおけるRhizopus oryzae特異的分泌抗原の有用性の検討2016

    • Author(s)
      佐藤佳奈子、金子幸弘、掛屋 弘、他
    • Organizer
      第60回日本医真菌学会総会・学術集会
    • Place of Presentation
      東京都立産業貿易センター:東京都
    • Year and Date
      2016-10-01
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] ムーコル症を診断/検査するためのツール及び方法2016

    • Inventor(s)
      公立大学法人大阪市立大学、国立感染症研究所
    • Industrial Property Rights Holder
      公立大学法人大阪市立大学、国立感染症研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-11-24
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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