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Elucidation of macrolide resistance mechanism and virulence of Streptococcus pyogenes focused on phage DNA

Research Project

Project/Area Number 16K08782
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionNagoya City University

Principal Investigator

Hasegawa Tadao  名古屋市立大学, 大学院医学研究科, 教授 (10314014)

Co-Investigator(Kenkyū-buntansha) 井坂 雅徳  名古屋市立大学, 大学院医学研究科, 助教 (40336673)
立野 一郎  名古屋市立大学, 大学院医学研究科, 講師 (50311642)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsA群レンサ球菌 / マクロライド / ファージ / mef(A) / msr(D) / 薬剤耐性 / 病原性 / 病原因子 / 二成分制御系 / 劇症型感染症
Outline of Final Research Achievements

We elucidated the macrolide resistance mechanism and virulence of Streptococcus pyogenes focused on phage DNA.
The roles of mef(A)/mef(E) genes that encode drug efflux pump in macrolide resistance are not much; however, those of msr(D) genes that exit downstream of mef(A)/mef(E) genes play more important roles. In addition, the degree of macrolide resistance is correlated with the nucleotide difference of msr(D) genes. Finally, macrolide resistance is suggested to be under control of two-component regulatory systems that sense outer signals.

Academic Significance and Societal Importance of the Research Achievements

今回の結果は従来マクロライド耐性メカニズムの一つとして定説であったmef(A)/mef(E)による薬剤の排出メカニズムの関与は少なく、mef(A)/mef(E)遺伝子それぞれのゲノム直下にあるmsr(D)の重要性を確立したのみならず、それぞれのmsr(D)の塩基配列の違いが菌のマクロライド耐性の度合いと相関することを世界で初めて明らかにしたことが学術的な意義である。マクロライドは世界で広く使用されている抗生物質のひとつであり、薬剤耐性を克服するうえでその真の耐性メカニズムを明らかにしたことは今後の創薬にも貢献することが期待される。

Report

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

Research Products

(4 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [Journal Article] Homologous role of CovRS two-component regulatory system in NAD+ -glycohydrolase activity in Streptococcus dysgalactiae subsp. equisimilis as in Streptococcus pyogenes.2019

    • Author(s)
      Hasegawa T, Matsumoto M, Hata N, Yano H, Isaka M, Tatsuno I.
    • Journal Title

      APMIS

      Volume: 127 Pages: 87-92

    • DOI

      10.1111/apm.12914

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Predominance of msr(D), Which Is More Effective as mef(A)-Associated Than mef(E)-Associated, Over mef(A)/mef(E) in Macrolide Resistance in Streptococcus pyogenes2018

    • Author(s)
      Tatsuno Ichiro、Isaka Masanori、Masuno Katsuaki、Hata Nanako、Matsumoto Masakado、Hasegawa Tadao
    • Journal Title

      Microb Drug Resist.

      Volume: in press Pages: 1089-1097

    • DOI

      10.1089/mdr.2017.0277

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of clinically isolated Streptococcus pyogenes from balanoposthitis patients with special emphasis on emm89 isolates.2017

    • Author(s)
      Hasegawa T, Hata N, Matsui H, Isaka M, Tatsuno I
    • Journal Title

      J. Med. Microbiol.

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] A群レンサ球菌におけるmef(A), mef(E)マクロライド耐性システムの解析2017

    • Author(s)
      長谷川忠男、松本昌門、松井秀之、井坂雅徳、立野一郎
    • Organizer
      第54回日本細菌学会中部支部総会
    • Related Report
      2017 Research-status Report

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

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