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Fundamental research to establish a risk diagnostic method for highly multidrug-resistant Staphylococcus aureus of oral origin.

Research Project

Project/Area Number 21K09858
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionHiroshima University

Principal Investigator

MATSUO MIKI  広島大学, 医系科学研究科(歯), 准教授 (20527048)

Co-Investigator(Kenkyū-buntansha) 小松澤 均  広島大学, 医系科学研究科(歯), 教授 (90253088)
菅井 基行  国立感染症研究所, 薬剤耐性研究センター, センター長 (10201568)
LE NGUYEN・TRA・MI (レ グエントラミ)  広島大学, 医系科学研究科(歯), 助教 (20897904)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords薬剤耐性 / 黄色ブドウ球菌 / バクテリオシン / 口腔 / 多剤耐性 / 高度耐性 / 薬剤耐性菌
Outline of Research at the Start

本研究では、全身感染症の起点となる口腔由来黄色ブドウ球菌について、抗菌剤ごとの高度薬剤耐性黄色ブドウ球菌の出現割合や遺伝子変異と病原性の相関を網羅的に検証する。さらに、内在性の遺伝子変異により高度薬剤耐性能を持つ黄色ブドウ球菌 (内在変異型高度耐性菌) の市中における潜在率の検証も行う。これらの基盤研究により、将来的に口腔由来黄色ブドウ球菌の高度薬剤耐性化リスクのトリアージを行うことで診断法の確立を目指す。リスク診断法を確立することで、耐性菌出現を起こさない適切な抗菌剤の使用量と頻度の情報を医療現場に提供することで、口腔由来の薬剤耐性菌出現を抑制することも視野に入れている。

Outline of Final Research Achievements

The aim of this study was to verify that endogenous genetic variation affects the drug susceptibility of Staphylococcus aureus, and genomic analysis of approximately 100 isolates of S. aureus showed a common polymorphism in the graRS, dlt and mprF genes, which affected the susceptibility of positive charges to antimicrobial substances, and that this polymorphism was not necessarily consistent with ST classification (Under review). On the other hand, we found four bacteriocins, bacterial-derived antimicrobial factors that were found to be effective against drug-resistant S. aureus. Two of these bacteriocins were from the genus Staphylococcus, which was isolated from humans in the process of isolating S. aureus in the above project, suggesting that some indigenous bacteria are responsible for the elimination of drug-resistant S. aureus.

Academic Significance and Societal Importance of the Research Achievements

近年薬剤耐性菌問題が深刻化しており、特に多剤耐性黄色ブドウ球菌 (MRSA) は常在細菌であるとともに、多種多様な病原性因子を持つ病原細菌である。一般的に黄色ブドウ球菌はプラスミド等から外来性に薬剤耐性を獲得することは知られているが、本研究から薬剤耐性はSTに依存せず、特定の遺伝子多型性により影響を受けることが示唆され、この知見は、現在のST分類による薬剤耐性のリスク判定に加え、特定の遺伝子パターンにも着目した解析が必要であることを提案できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (20 results)

All 2024 2023 2022 2021

All Journal Article (13 results) (of which Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Triterpenoid saponin from Panax ginseng increases the sensitivity of methicillin-resistant Staphylococcus aureus to β-lactam and aminoglycoside antibiotics.2024

    • Author(s)
      [Sakura Tsutamoto,Yuina Iwasaki,Akari Shinohara,Risa Imamiya,Keiichi Samukawa,Miki Kawada-Matsuo,Hitoshi Komatsuzawa,Yui Yamada,Kouki Mandokoro,Hiroshi Iwao,Yasuhiko Horiguchi,Mayuko Osada-Oka]
    • Journal Title

      Microbiology spectrum

      Volume: 22 Issue: 6

    • DOI

      10.1128/spectrum.03227-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Opposing genetic polymorphisms of two ABC transporters contribute to the variation of nukacin resistance in Streptococcus mutans.2024

    • Author(s)
      [Naoki Sadaoka,Mi Nguyen-Tra Le,Miki Kawada-Matsuo,Sopongselamuny Eng,Takeshi Zendo,Jun Nakanishi,Katsuhiro Takeda,Hideki Shiba,Hitoshi Komatsuzawa]
    • Journal Title

      Applied and environmental microbiology

      Volume: 90

    • DOI

      10.1128/aem.02084-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral and rectal colonization of methicillin-resistant Staphylococcus aureus in long-term care facility residents and their association with clinical status.2024

    • Author(s)
      [Satoru Kusaka,Azusa Haruta,Miki Kawada-Matsuo,Mi Nguyen-Tra Le,Mineka Yoshikawa,Toshiki Kajihara,Koji Yahara,Junzo Hisatsune,Ryota Nomura,Kazuhiro Tsuga,Hiroki Ohge,Motoyuki Sugai,Hitoshi Komatsuzawa]
    • Journal Title

      Microbiology and immunology

      Volume: 68 Issue: 3 Pages: 75-89

    • DOI

      10.1111/1348-0421.13111

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disinfectant Susceptibility of Third-Generation-Cephalosporin/Carbapenem-Resistant Gram-Negative Bacteria Isolated from the Oral Cavity of Residents of Long-Term-Care Facilities2023

    • Author(s)
      [Azusa Haruta,Miki Kawada-Matsuo,Mi Nguyen-Tra Le,Mineka Yoshikawa,Toshiki Kajihara,Koji Yahara,Norikazu Kitamura,Shoko Kutsuno,Chika Arai,Maho Takeuchi,Yo Sugawara,Junzo Hisatsune,Kazuhiro Tsuga,Hiroki Ohge,Motoyuki Sugai,Hitoshi Komatsuzawa]
    • Journal Title

      Applied and Environmental Microbiology

      Volume: 89 Issue: 1

    • DOI

      10.1128/aem.01712-22

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different CprABC amino acid sequences affect nisin A susceptibility in Clostridioides difficile isolates.2023

    • Author(s)
      [Noriaki Ide,Miki Kawada-Matsuo,Mi Nguyen-Tra Le,Junzo Hisatsune,Hiromi Nishi,Toshinori Hara,Norikazu Kitamura,Seiya Kashiyama,Michiya Yokozaki,Hiroyuki Kawaguchi,Hiroki Ohge,Motoyuki Sugai,Hitoshi Komatsuzawa]
    • Journal Title

      PloS one

      Volume: 18 Issue: 1 Pages: e0280676-e0280676

    • DOI

      10.1371/journal.pone.0280676

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral and Rectal Colonization by Antimicrobial-Resistant Gram-Negative Bacteria and Their Association with Death among Residents of Long-Term Care Facilities: A Prospective, Multicenter, Observational, Cohort Study2023

    • Author(s)
      [Toshiki Kajihara,Koji Yahara,Mineka Yoshikawa,Azusa Haruta,Miki Kawada-Matsuo,Mi Nguyen-Tra Le,Chika Arai,Maho Takeuchi,Norikazu Kitamura,Yo Sugawara,Junzo Hisatsune,Shizuo Kayama,Kouji Ohta,Kazuhiro Tsuga,Hitoshi Komatsuzawa,Hiroki Ohge,Motoyuki Sugai]
    • Journal Title

      Gerontology

      Volume: 69 Issue: 3 Pages: 261-272

    • DOI

      10.1159/000525759

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation of Streptococcus mutans temperate bacteriophage with broad killing activity to S. mutans clinical isolates2023

    • Author(s)
      [Katsuhito Sugai,Miki Kawada-Matsuo,Mi Nguyen-Tra Le,Yo Sugawara,Junzo Hisatsune,Jumpei Fujiki,Hidetomo Iwano,Kotaro Tanimoto,Motoyuki Sugai,Hitoshi Komatsuzawa]
    • Journal Title

      iScience

      Volume: 26 Issue: 12 Pages: 108465-108465

    • DOI

      10.1016/j.isci.2023.108465

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete genome sequence of cfr(B)-carrying Enterococcus raffinosus isolated from bile in a patient in Japan2023

    • Author(s)
      [Kasumi Ishida-Kuroki,Junzo Hisatsune,Takaya Segawa,Yo Sugawara,Kanako Masuda,Kayoko Tadera,Seiya Kashiyama,Michiya Yokozaki,Mi Nguyen-Tra Le,Miki Kawada-Matsuo,Hiroki Ohge,Hitoshi Komatsuzawa,Motoyuki Sugai]
    • Journal Title

      Journal of Global Antimicrobial Resistance

      Volume: 34 Pages: 43-45

    • DOI

      10.1016/j.jgar.2023.06.004

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive Analysis of Bacteriocins Produced by the Hypermucoviscous Klebsiella pneumoniae Species Complex.2023

    • Author(s)
      [Mi Nguyen-Tra Le,Thao Huu-Huong Nguyen,Van Minh Trinh,Tam Phuc-Bao Nguyen,Miki Kawada-Matsuo,Shizuo Kayama,Motoyuki Sugai,Hitoshi Komatsuzawa]
    • Journal Title

      Microbiology spectrum

      Volume: 3 Issue: 3 Pages: 00863-23

    • DOI

      10.1128/spectrum.00863-23

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete genome sequence of optrA-carrying Enterococcus faecalis isolated from open pus in a Japanese patient2023

    • Author(s)
      Segawa Takaya、Hisatsune Junzo、Ishida-Kuroki Kasumi、Sugawara Yo、Masuda Kanako、Tadera Kayoko、Kashiyama Seiya、Yokozaki Michiya、Le Mi Nguyen-Tra、Kawada-Matsuo Miki、Ohge Hiroki、Komatsuzawa Hitoshi、Sugai Motoyuki
    • Journal Title

      Journal of Global Antimicrobial Resistance

      Volume: 33 Pages: 276-278

    • DOI

      10.1016/j.jgar.2023.04.006

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficiency of Antimicrobial Peptides Against Multidrug-Resistant Staphylococcal Pathogens2022

    • Author(s)
      Mi Nguyen-Tra Le, Miki Kawada-Matsuo, Hitoshi Komatsuzawa
    • Journal Title

      Front Microbiol.

      Volume: 13 Pages: 930629-930629

    • DOI

      10.3389/fmicb.2022.930629

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] Complete sequences of epidermin and nukacin encoding plasmids from oral-derived Staphylococcus epidermidis and their antibacterial activity2022

    • Author(s)
      Kenta Nakazono, Mi Nguyen-Tra Le, Miki Kawada-Matsuo, Noy Kimheang, Junzo Hisatsune , Yuichi Oogai , Masanobu Nakata , Norifumi Nakamura, Motoyuki Sugai , Hitoshi Komatsuzawa
    • Journal Title

      PLoS One

      Volume: 17(1) Issue: 1 Pages: e0258283-e0258283

    • DOI

      10.1371/journal.pone.0258283

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Open Access
  • [Journal Article] Antibacterial Peptides Resistance in Staphylococcus aureus: Various Mechanisms and the Association with Pathogenicity2021

    • Author(s)
      Kawada-Matsuo M, Le MN, Komatsuzawa H.
    • Journal Title

      Genes (Basel).

      Volume: 12(10) Issue: 10 Pages: 1527-1527

    • DOI

      10.3390/genes12101527

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] アラニントランスポーターCycAは 菌体表層チャージを介したカチオン性抗菌剤への耐性に関与する2024

    • Author(s)
      鈴木 優仁, 松尾 美樹, Le Nguyen Tra Mi, Ton That Thuan Vy, 小松澤 均
    • Organizer
      第97回日本細菌学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 脂肪酸の黄色ブドウ球菌および化膿レンサ球菌に対する抗菌活性2024

    • Author(s)
      大段慶十朗, 鈴木優仁, 松尾美樹, Mi Nguyen-Tra Le, 荒井千夏, 久恒順三,菅原庸3, 相川友直, 菅井基行, 小松澤 均
    • Organizer
      第97回日本細菌学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Novel candidates of antimicrobial peptides (AMPs) against MRSA and  Resistance mechanisms of MRSA against AMPs.2023

    • Author(s)
      Miki Kawada-Matsuo, Mi Nguyen-Tra Le, Hitoshi Komatsuzawa
    • Organizer
      The 15th Korea-Japan International Symposium on Microbiology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 表皮ブドウ球菌由来バクテリオシン Pep5 の解析および黄色ブドウ球菌における菌体表層チャージを介した Pep5 耐性因子の検証2023

    • Author(s)
      鈴木優仁、松尾美樹、Mi Nguyen-Tra Le、小松澤均
    • Organizer
      第66回日本ブドウ球菌研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] 黄色ブドウ球菌における菌体表層チャージを介した新規バクテリオシン耐性メカニズムの解明2023

    • Author(s)
      鈴木優仁、松尾美樹、Mi Nguyen-Tra Le、小松澤均
    • Organizer
      第96回日本細菌学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Complete sequences of bacteriocin plasmids of S. epidermidis and their antibacterial activity2022

    • Author(s)
      Miki Kawada-Matsuo Mi Nguyen-Tra Le Hitoshi Komatsuzawa
    • Organizer
      第95回 日本細菌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Identification of a new resistance factor against nukacins in Streptococcus mutans2021

    • Author(s)
      Miki Kawada-Matsuo Mi Nguyen-Tra Le Hitoshi Komatsuzawa
    • Organizer
      第63回 歯科基礎医学会総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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