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Horizontal tranmission of antimicrobial gene among biofilm-producing Escherichia coli in the intesine of children

Research Project

Project/Area Number 20K08161
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKagoshima University

Principal Investigator

Junichiro Nishi  鹿児島大学, 医歯学域医学系, 教授 (40295241)

Co-Investigator(Kenkyū-buntansha) 藺牟田 直子  鹿児島大学, 医歯学域医学系, 助教 (00643470)
児玉 祐一  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (20535695)
大岡 唯祐  鹿児島大学, 医歯学域医学系, 准教授 (50363594)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大腸菌 / 基質特異性拡張型β-ラクタマーゼ / 腸管凝集性大腸菌(EAEC) / CTX-M / K1莢膜遺伝子 / バイオフィルム / 菌血症 / 腸管凝集性大腸菌 / AmpC型β-ラクタマーゼ / ESBL / 薬剤耐性 / 集団保育
Outline of Research at the Start

我々は2001年からの小児腸管由来大腸菌株の解析で、EAECの一部が、ESBL産生大腸菌の出現当初から継続してESBL CTX-M遺伝子を保有していたことを報告した。また我々は、より強いバイオフィルム形成能をもつEAECが新たにCTX-M遺伝子を獲得しつつあることを最近明らかにしている。EAECは乳幼児が感染・保菌しやすく、またバイオフィルム形成能が高く付着性が強いため集団保育で広がり、ESBL遺伝子伝播のリザーバーとなっていると考えられる。本研究では、CTX-M産生EAEC株をモデルとして、バイオフィルムが薬剤耐性遺伝子の水平伝播を促進するメカニズムを解明し、薬剤耐性菌出現の新規予防薬開発につなげる。

Outline of Final Research Achievements

Among a total of 354 ESBL (extended-spectrum β-lactamase) CTX-M gene-positive Escherichia coli strains from diarrheal children in Kagoshima (2001-2009), 41 strains (11.6%) of biofilm-producing AggR-positive enteroaggregative E. coli and 43 strains (12.1%) of invasive K1 capsular gene-positive strains were detected. Furthermore, among a total of 143 biofilm-producing atypical EAEC without AggR (2011-2019), nine strains (6.3%) of ESBL CTX-M gene-positive E. coli and one strains (0.7%) of plasmid-borne AmpC β-lactamase gene-positive E. coli were detected, of which one strain (11.1%) possessed the K1 capsular gene.

Academic Significance and Societal Importance of the Research Achievements

小児下痢症患児由来大腸菌から検出されるESBL(基質特異性拡張型β-ラクタマーゼ)産生菌のうちバイオフィルム形成能の強い腸管凝集性大腸菌(typical EAEC)が11.6%を占め、またこれまで注目されていないatypical EAECにも薬剤耐性遺伝子保有大腸菌がみられることが明らかになった。また、これらの株の中には侵襲性に関わるK1莢膜遺伝子を一定の割合で保有していた。小児の腸管内で薬剤耐性遺伝子と病原遺伝子の水平伝播が活発に進んでおり、今後薬剤耐性遺伝子と病原遺伝子を併せ持った病原性の強い大腸菌の出現が懸念されるため、これらの株を選択しないよう小児への経口抗菌薬の適正使用が望まれる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021 2020

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (5 results)

  • [Journal Article] Invasive Haemophilus influenzae disease among adults in Japan during 2014–20182023

    • Author(s)
      Hachisu Y, Tamura K, Murakami K, Fujita J, Watanabe H, Tanabe Y, Kuronuma K, Kubota T, Oshima K, Maruyama T, Kasahara K, Nishi J, Abe S, Nakamura M, Kubota M, Hirai S, Ishioka T, Ikenoue C, Fukusumi M, Sunagawa T, Suzuki M, Akeda Y, Oishi K; Adult IHD Study Group.
    • Journal Title

      Infection.

      Volume: 51 Issue: 2 Pages: 355

    • DOI

      10.1007/s15010-022-01885-w

    • URL

      https://pure.teikyo.jp/en/publications/df147b77-ce87-4379-a9ce-dcf23022f797

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic and phylogenetic characterization of Elizabethkingia anophelis strains: The first two cases of life-threatening infection in Japan2023

    • Author(s)
      Ichiki K, Ooka T, Shinkawa T, Inoue S, Hayashida M, Nakamura D, Akimoto M, Yoshimitsu M, Kawamura H, Nakamura M, Obama Y, Gotoh Y, Hayashi T, Nishi J, Ishitsuka K
    • Journal Title

      J Infect Chemother

      Volume: 29(4) Issue: 4 Pages: 376-383

    • DOI

      10.1016/j.jiac.2023.01.005

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pneumococcal meningitis in adults in 2014-2018 after introduction of pediatric 13-valent pneumococcal conjugate vaccine in Japan.2022

    • Author(s)
      Chang B, Tamura K, Fujikura H, Watanabe H, Tanabe Y, Kuronuma K, Fujita J, Oshima K, Maruyama T, Abe S, Kasahara K, Nishi J, Kubota T, Kinjo Y, Serizawa Y, Shimbashi R, Fukusumi M, Shimada T, Sunagawa T, Suzuki M, Oishi K; Adult IPD Study Group.
    • Journal Title

      Sci Rep.

      Volume: 12 Issue: 1 Pages: 3066-3066

    • DOI

      10.1038/s41598-022-06950-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic changes in clinical characteristics and serotype distribution of invasive pneumococcal disease among adults in Japan after introduction of the pediatric 13-valent pneumococcal conjugate vaccine in 2013-2019.2022

    • Author(s)
      Tamura K, Chang B, Shimbashi R, Watanabe H, Tanabe Y, Kuronuma K, Oshima K, Maruyama T, Fujita J, Abe S, Kasahara K, Nishi J, Kubota T, Kinjo Y, Fujikura H, Fukusumi M, Shimada T, Sunagawa T, Suzuki M, Yamamoto Y, Oishi K.
    • Journal Title

      Vaccine

      Volume: 40 Issue: 24 Pages: 3338-3344

    • DOI

      10.1016/j.vaccine.2022.04.062

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A <i>Salmonella enterica</i> Serovar Oranienburg Clone Caused a Cluster of Bacteremia Cases in Persons With No Recognizable Underlying Diseases in Japan2022

    • Author(s)
      Ooka Tadasuke、Gotoh Yasuhiro、Hatanaka Shigeki、... Ogura Yoshitoshi、et al.
    • Journal Title

      Open Forum Infectious Diseases

      Volume: 10 Issue: 1

    • DOI

      10.1093/ofid/ofac695

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diversification of Escherichia albertii H-Antigens and Development of H-Genotyping PCR2021

    • Author(s)
      Nakae Koji、Ooka Tadasuke、Murakami Koichi、Hara-Kudo Yukiko、Imuta Naoko、Gotoh Yasuhiro、Ogura Yoshitoshi、Hayashi Tetsuya、Okamoto Yasuhiro、Nishi Junichiro
    • Journal Title

      Frontiers in Microbiology

      Volume: 12 Pages: 737979-737979

    • DOI

      10.3389/fmicb.2021.737979

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of antibacterial agents against cell-invading bacteria such as Streptococcus pyogenes and Haemophilus influenzae2021

    • Author(s)
      IuchiH, Ohori J, Kiyama S, Imura N, Nishi J, Kurono Y, Yamashita M
    • Journal Title

      BMC Microbiology

      Volume: 21 Issue: 1 Pages: 148-155

    • DOI

      10.1186/s12866-021-02217-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution and Variation of Serotypes and Pneumococcal Surface Protein A Clades of Streptococcus pneumoniae Strains Isolated From Adult Patients With Invasive Pneumococcal Disease in Japan2021

    • Author(s)
      Chang Bin、Kinjo Yuki、Morita Masatomo、Tamura Kosuke、Watanabe Hiroshi、Tanabe Yoshinari、Kuronuma Koji、Fujita Jiro、Oshima Kengo、Maruyama Takaya、Abe Shuichi、Kasahara Kei、Nishi Junichiro、Kubota Tetsuya、Ohnishi Makoto、Suga Shigeru、Oishi Kazunori
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 617573-617573

    • DOI

      10.3389/fcimb.2021.617573

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoosmotic stress induces flagellar biosynthesis and swimming motility in Escherichia albertii2020

    • Author(s)
      Ikeda T, Shinagawa T, Ito T, Ohno Y, Kubo A, Nishi J, Gotoh Y, Ogura Y, Ooka T, Hayashi T
    • Journal Title

      Commun Biol

      Volume: 3(1) Issue: 1 Pages: 87-87

    • DOI

      10.1038/s42003-020-0816-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of polymicrobial bacteremia due to lung abscess after respiratory syncytial virus infection2020

    • Author(s)
      Shogo Otake, Takahiro Yamaguchi, Naoko Imuta, Junichiro Nishi, Masashi Kasai
    • Journal Title

      Pediatrics International

      Volume: 62(8) Issue: 8 Pages: 994-996

    • DOI

      10.1111/ped.14220

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in adults, Japan, 2013-20172020

    • Author(s)
      Shimbashi R, Suzuki M, Chang B, Watanabe H, Tanabe Y, Kuronuma K, Oshima K, Maruyama T, Takeda H, Kasahara K, Fujita J, Nishi J, Kubota T, Tanaka-Taya K, Matsui T, Sunagawa T, Oishi K
    • Journal Title

      Emerg Infect Dis

      Volume: 26(10) Issue: 10 Pages: 2378-2386

    • DOI

      10.3201/eid2610.191531

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸菌における astA 遺伝子バリアントの同定およびその分布2023

    • Author(s)
      大岡唯祐、後藤恭宏、林 哲也、西 順一郎
    • Organizer
      第96回日本細菌学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 小児下痢症患児由来大腸菌における下痢原性大腸菌の頻度と推移(2011~2019年)2022

    • Author(s)
      藺牟田直子、児玉祐一、中村隼人、大岡唯祐、西 順一郎
    • Organizer
      第96回日本感染症学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 小児下痢症患児由来大腸菌における下痢原性大腸菌の頻度とESBL 産生菌の検討(2011~2019年)2022

    • Author(s)
      藺牟田直子、児玉祐一、西 順一郎
    • Organizer
      第54回日本小児感染症学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 血液由来大腸菌による病原遺伝子とESBL CTX-M遺伝子の分布2021

    • Author(s)
      中村 隼人、藺牟田直子、大岡唯祐、西 順一郎.
    • Organizer
      第95回日本感染症学会学術講演会・第69回日本化学療法学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 小児腸管由来大腸菌におけるESBL CTX-M遺伝子保有大腸菌の頻度と病原遺伝子の検討(2001~2019)2021

    • Author(s)
      藺牟田直子、中村隼人、大岡唯祐、西 順一郎
    • Organizer
      第95回日本感染症学会学術講演会・第69回日本化学療法学会総会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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