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Elucidation of carbapenem-resistant Klebsiella pneumoniae emerging mechanisms to prevent the infection

Research Project

Project/Area Number 17K10027
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionNara Medical University

Principal Investigator

Nakano Ryuichi  奈良県立医科大学, 医学部, 准教授 (80433712)

Co-Investigator(Kenkyū-buntansha) 矢野 寿一  奈良県立医科大学, 医学部, 教授 (20374944)
遠藤 史郎  国際医療福祉大学, 国際医療福祉大学塩谷病院, 教授 (40614491)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsカルバペネム耐性腸内細菌科(CRE) / カルバペネマーゼ産生腸内細菌科(CPE) / ゲノム型 / プラスミド型 / 病原因子 / 検出法 / ディスク法 / LAMP法 / カルバペネム耐性肺炎桿菌 / カルバペネマーゼ / ポーリン欠損 / NmcA産生菌 / カルバペネマーゼ非産生CRE / 腸内細菌科 / NMC-A / 薬剤耐性菌 / 肺炎桿菌
Outline of Final Research Achievements

In this study, we characterized clinical isolates of carbapenem-resistant Enterobacteriaceae (CRE) in Japan, in terms of their carbapenem resistance mechanisms, genotypes, plasmid types, and virulence determinants. Molecular analysis indicated that carbapenemase-producing Klebsiella pneumoniae were harboring IMP type carbapenemase. Mechanisms of non-carbapenemase-producing-CRE was production of ESBLs or AmpC in combination with porin loss/deficiency. Our results also show that highly virulent carbapenemase-producing K. pneumoniae clinical isolates are emerging in Japan.
Furthermore, we have developed a loop-mediated isothermal amplification (LAMP) method and double-disk synergy test for detection of NmcA carbapenemase producing Enterobacteriaceae with high specificity and sensitivity. It may be routinely applied for detection of carbapenemase producers in the clinical laboratory.

Academic Significance and Societal Importance of the Research Achievements

本邦の医療機関で分離されるCREについて、海外とは異なる独特な特徴が明らかになった。IMP型カルバペネマーゼが優性であり、遺伝学的特徴からプラスミドに共通性があった。プラスミドの伝達性も高い事から菌種を越えた拡がりの可能性も考えられた。また病原性肺炎桿菌が多く含まれていたことからも、臨床現場においてこの耐性株の拡がりについては注視していく必要があるだろう。
臨床現場での応用を想定したCREの検出法も開発した。感度・特異度ともに高いため、迅速検出や診断に貢献することが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (41 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 6 results) Presentation (27 results) (of which Int'l Joint Research: 5 results,  Invited: 10 results)

  • [Journal Article] Trends and molecular characteristics of carbapenemase-producing Enterobacteriaceae in Japanese hospital from 2006 to 20152020

    • Author(s)
      Eda Ryotaro、Nakamura Masaki、Takayama Yoko、Maehana Shotaro、Nakano Ryuichi、Yano Hisakazu、Kitasato Hidero
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: In Press Issue: 7 Pages: 667-671

    • DOI

      10.1016/j.jiac.2020.02.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Filifactor alocis brain abscess identified by 16S ribosomal RNA gene sequencing: A case report2020

    • Author(s)
      Hishiya Naokuni、Uno Kenji、Amano Masayuki、Asada Kiyokazu、Masui Katsuya、Ishida Yasuhito、Suzuki Yuki、Hirai Nobuyasu、Nakano Akiyo、Nakano Ryuichi、Kasahara Kei、Yano Hisakazu、Mikasa Keiichi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 26 Issue: 2 Pages: 305-307

    • DOI

      10.1016/j.jiac.2019.09.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Environmental presence and genetic characteristics of carbapenemase-producing Enterobacteriaceae from hospital sewage and river water in the Philippines.2020

    • Author(s)
      Suzuki Y, Nazareno PJ, Nakano R, Mondoy M, Nakano A, Bugayong MP, Bilar J, Perez M 5th, Medina EJ, Saito-Obata M, Saito M, Nakashima K, Oshitani H, Yano H
    • Journal Title

      Appl Environ Microbiol

      Volume: 88 Issue: 2

    • DOI

      10.1128/aem.01906-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Novel Mismatched PCR-Restriction Fragment Length Polymorphism Assay for Rapid Detection of gyrA and parC Mutations Associated With Fluoroquinolone Resistance in Acinetobacter baumannii2020

    • Author(s)
      Kakuta Naoki、Nakano Ryuichi、Nakano Akiyo、Suzuki Yuki、Tanouchi Ayako、Masui Takashi、Horiuchi Saori、Endo Shiro、Kakuta Risako、Ono Yasuo、Yano Hisakazu
    • Journal Title

      Annals of Laboratory Medicine

      Volume: 40 Issue: 1 Pages: 27-27

    • DOI

      10.3343/alm.2020.40.1.27

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison between IMP carbapenemase-producing Enterobacteriaceae and non-carbapenemase-producing Enterobacteriaceae: a multicentre prospective study of the clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae.2020

    • Author(s)
      Hayakawa K, Nakano R, Hase R, Shimatani M, Kato H, Hasumi J, Doi A, Sekiya N, Nei T, Okinaka K, Kasahara K, Kurai H, Nagashima M, Miyoshi-Akiyama T, Kakuta R, Yano H, Ohmagari N.
    • Journal Title

      J Antimicrob Chemother.

      Volume: 75 Issue: 3 Pages: 697-708

    • DOI

      10.1093/jac/dkz501

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indication of Minimum Inhibitory Concentration of β-Lactam Antimicrobials for the Primary Extraction of IMP-Producing <i>Enterobacteriaceae</i>2019

    • Author(s)
      Saito Kyoichi、Nakamura Kiwamu、Harada Rie、Nakano Ryuichi、Yano Hisakazu、Kanemitsu Keiji
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 72 Issue: 1 Pages: 68-70

    • DOI

      10.7883/yoken.JJID.2018.297

    • NAID

      130007577804

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2019-01-31
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biofilm-forming by carbapenem resistant Enterobacteriaceae may contribute to the blood stream infection.2019

    • Author(s)
      Nakano R, Yaita K, Gotoh K, Iwahashi J, Sakai Y, Horita R, Yano H, Watanabe H
    • Journal Title

      Int J Mol Sci

      Volume: 20 Issue: 23 Pages: 5954-5954

    • DOI

      10.3390/ijms20235954

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of the inoculum size effects in blaIMP-6 and plasmid-mediated quinolone resistance gene-positive Enterobacteriaceae in Japan.2019

    • Author(s)
      Ogawa Y, Nakano R, Kasahara K, Mizuno T, Hirai N, NakanoA, Suzuki Y, Kakuta N, Masui T, Yano H, Mikasa K
    • Journal Title

      PLoS ONE

      Volume: 14 Issue: 11 Pages: e0225210-e0225210

    • DOI

      10.1371/journal.pone.0225210

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emergence of IMP-34 and OXA-58-producing carbapenem-resistant Acinetobacter colistiniresistens2019

    • Author(s)
      Suzuki Y, Endo S, Nakano R, Nakano A, Saito K, Kakuta R, Kakuta N, Horiuchi S, Yano H, and Kaku M
    • Journal Title

      Antimicrob Agents Chemother

      Volume: in press Issue: 6

    • DOI

      10.1128/aac.02633-18

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and mechanism of fluoroquinolone resistance in clinical isolates of Proteus mirabilis in Japan2019

    • Author(s)
      Nakano Ryuichi、Nakano Akiyo、Abe Michiko、Nagano Noriyuki、Asahara Miwa、Furukawa Taiji、Ono Yasuo、Yano Hisakazu、Okamoto Ryoichi
    • Journal Title

      Heliyon

      Volume: 5 Issue: 3 Pages: e01291-e01291

    • DOI

      10.1016/j.heliyon.2019.e01291

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rat-Bite Fever in Human with Streptobacillus notomytis Infection, Japan2018

    • Author(s)
      Ogawa Yoshihiko、Kasahara Kei、Lee Sang-Tae、Ito Takamitsu、Hasegawa Hideo、Hirose Sachie、Santo Shigeru、Yoshida Atsushi、Nakano Ryuichi、Yano Hisakazu、Mikasa Keiichi
    • Journal Title

      Emerging Infectious Diseases

      Volume: 24 Issue: 7 Pages: 1377-1379

    • DOI

      10.3201/eid2407.171580

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Emergence of VIM-2-producing Citrobacter freundii in Japan2018

    • Author(s)
      Ando S, Nakano R, Kuchibiro T, Yamasaki K, Suzuki Y, Nakano A, Mizuno T, Kasahara K, Yano H
    • Journal Title

      Infectious Diseases (Lond)

      Volume: 50 Issue: 11-12 Pages: 862-863

    • DOI

      10.1080/23744235.2018.1498592

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rapid Identification of bla(IMP-1) and bla(IMP-6) by Multiplex Amplification Refractory Mutation System PCR2018

    • Author(s)
      Nakano A, Nakano R, Suzuki Y, Saito K, Kasahara K, Endo S, Yano H
    • Journal Title

      Ann Lab Med

      Volume: 38 Issue: 4 Pages: 378-380

    • DOI

      10.3343/alm.2018.38.4.378

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of AmpR in the High Expression of the Plasmid-Encoded AmpC β-Lactamase CFE-1.2017

    • Author(s)
      Nakano R, Nakano A, Yano H, Okamoto R
    • Journal Title

      mSphere

      Volume: 2 Issue: 4

    • DOI

      10.1128/msphere.00192-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 誘導実験にともなうカルバペネマーゼNmcAの発現機構の変化2020

    • Author(s)
      中野竜一、中野章代、山田友紀、成田和也、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Enterobacter属のカルバペネム耐性機構を識別するディスク法の開発2020

    • Author(s)
      中野竜一、中野章代、鈴木由希、山田友紀、諏訪部章、矢野寿一
    • Organizer
      第31回日本臨床微生物学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] パネルディスカッション4 GNR耐性菌検査法を極める; 腸内細菌科細菌 AmpC産生菌の検出を極める2020

    • Author(s)
      中野竜一
    • Organizer
      第31回日本臨床微生物学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] カルバペネム耐性Enterobacter属の耐性機構を識別するディスク法の開発2019

    • Author(s)
      中野竜一、中野章代、鈴木由希、水野友貴、山田友紀、諏訪部章、矢野寿一
    • Organizer
      第67回日本化学療法学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] カルバペネマーゼNmcA産生株の誘導機構の解明2019

    • Author(s)
      中野竜一、中野章代、山田友紀、成田和也、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] カルバペネマーゼNMC-A産生株の耐性機構解明ならびに検出法の構築2019

    • Author(s)
      中野竜一、中野章代、山田友紀、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第93回日本感染症学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of loop-mediated isothermal amplification and double-disk synergy test for the detection of NmcA-producing Enterobacter cloacae complex2019

    • Author(s)
      R Nakano, A Nakano, Y Yamada, K Narita, Y Suzuki, A Suwabe, H Yano
    • Organizer
      29th European Congress of Clinical Microbiology & Infectious Diseases
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] シンポジウム4 薬剤耐性菌の分子疫学; One Healthの視点から見た薬剤耐性菌の分子疫学2019

    • Author(s)
      中野竜一
    • Organizer
      第67回日本化学療法学会西日本支部総会、第89回日本感染症学会西日本地方会学術集会、第62回日本感染症学会中日本地方会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] シンポジウム16 院内感染 病院から病院外へ 病院外から病院へ; 家畜とヒトにおけるESBL産生菌の現状2019

    • Author(s)
      中野竜一
    • Organizer
      第68回日本感染症学会東日本地方会学術集会、第66回日本化学療法学会東日本支部総会 合同学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 耐性菌について2019

    • Author(s)
      中野竜一
    • Organizer
      日臨技近畿支部微生物部門研修会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] カルバペネマーゼNMC-A産生株検出のためのディスク法ならびにLAMP法の検討2019

    • Author(s)
      中野竜一、中野章代、山田友紀、成田和也、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第30回日本臨床微生物学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 耐性菌シンポジウムB:耐性メカニズムにみる細菌の進化 β-ラクタム薬耐性菌の耐性獲得機構2019

    • Author(s)
      中野竜一
    • Organizer
      第30回日本臨床微生物学会総会・学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 薬剤耐性グラム陰性桿菌の最近の話題~カルバペネマーゼ新規検出法を含めて~2019

    • Author(s)
      中野竜一
    • Organizer
      第30回日本臨床微生物学会総会・学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] NMC-A産生株の調節遺伝子が関わる高度耐性機構の解明2018

    • Author(s)
      中野竜一、山田友紀、中野章代、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第66回日本化学療法学会西日本支部総会
    • Related Report
      2018 Research-status Report
  • [Presentation] フィリピンの環境水より分離されたカルバペネム耐性グラム陰性桿菌の解析2018

    • Author(s)
      中野竜一、鈴木由希、田内絢子、矢野寿一
    • Organizer
      第38回近畿腸管微生物研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] カルバペネマーゼNMC-A産生株の発現調節機構の解明2018

    • Author(s)
      中野竜一、山田友紀、中野章代、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第66回日本化学療法学会総会
    • Related Report
      2018 Research-status Report 2017 Research-status Report
  • [Presentation] Development of loop-mediated isothermal amplification and double-disk synergy test for the detection of NmcA-producing Enterobacter cloacae complex2018

    • Author(s)
      R Nakano, A Nakano, Y Yamada, K Narita, Y Suzuki, A Suwabe, H Yano
    • Organizer
      29th European Congress of Clinical Microbiology & Infectious Diseases
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 耐性菌対策に細菌学的検査をどう生かすか 基礎教室の立場から-グラム陰性菌について-2018

    • Author(s)
      中野竜一
    • Organizer
      第61回日本臨床検査医学会近畿支部総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] カルバペネム耐性腸内細菌科 細菌対策 UP TODATE カルバペネム耐性遺伝子の拡散機構2018

    • Author(s)
      中野竜一
    • Organizer
      第66回日本化学療法学会西日本支部総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 本邦で分離されたカルバペネマーゼNMC-A産生株の酵素産生機構の解明2018

    • Author(s)
      中野竜一、山田友紀、中野章代、成田和也、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミスマッチPCR-RFLP法による多剤耐性アシネトバクターの迅速検出法の開発2018

    • Author(s)
      中野竜一、中野章代、斎籐恭一、鈴木由希、安藤冴佳、水野友貴、遠藤史郎、斧康雄、矢野寿一
    • Organizer
      第29回日本臨床微生物学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Molecular characteristics of CTX-M β-lactamase-producing Escherichia coli isolated from livestock and human patients in Japan2018

    • Author(s)
      R Nakano, A Nakano, Nishisouzu, K Hikosaka, K Kasahara, Y Ono, H Yano
    • Organizer
      ECCMID2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of NMC-A expression in Enterobacter ludwigii first isolated in Japan2018

    • Author(s)
      R Nakano, Y Yamada, A Nakano, S Ando, T Mizuno, Y Suzuki, K Narita, A Suwabe, H Yano
    • Organizer
      ECCMID2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Emergence of multidrug-resistant Escherichia coli strain harbouring blaCTX-M-55, rmtB, and fosA3-encoding plasmid isolated from a food poisoning patient in Japan2018

    • Author(s)
      R Nakano, A Nakano, K Kasahara, Y Suzuki, S Ando, T Mizuno, K Mikasa, H Yano
    • Organizer
      ECCMID2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 本邦にて臨床より分離されたカルバペネマーゼNMC-A産生Enterobacter cloacaeについて2017

    • Author(s)
      中野竜一、山田友紀、中野章代、成田和也、斎藤恭一、鈴木由希、諏訪部章、矢野寿一
    • Organizer
      第65回日本化学療法学会西日本支部総会 合同学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 薬剤耐性菌について2017

    • Author(s)
      中野竜一
    • Organizer
      近畿臨床微生物講習会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 薬剤耐性菌、その問題点と識別について2017

    • Author(s)
      中野竜一
    • Organizer
      平成29年度第1回感染制御部門研修会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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