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Structure basis of reaction mechanism of beta-lactamases and new inhibitor search

Research Project

Project/Area Number 26460534
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionJosai International University

Principal Investigator

Nukaga Michiyoshi  城西国際大学, 薬学部, 准教授 (20251150)

Co-Investigator(Renkei-kenkyūsha) HOSHINO Tyuji  千葉大学, 薬学研究院, 准教授 (90257220)
Research Collaborator James R Knox  Univ. of Connecticut, Professor
Robert Bonomo  Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Professor
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords薬剤耐性 / 抗生物質 / 感染症 / 蛋白質 / 構造生物学 / X線結晶解析 / β-ラクタマーゼ / タンパク質 / β-ラクタム剤 / 分子動力学計算
Outline of Final Research Achievements

beta-Lactamases are the main cause of bacterial beta-lactams resistant.However, the emergence of novel beta-lactamases with direct carbapenem-hydrolyzing activity (carbapenemase) has contributed to an increased prevalence of carbapenem-resistant Enterobacteriaceae (CRE). In this study, we studied three subjects, which are concerned with beta-lactamase inhibition mechanism by carbapenems or carbapenemase inhibitor, avibactam.
(1) PenA class A carbapenemase PenA complex with avibactam. (2) Fox-4 plasmid mediated class C beta-lactamase in complex with avibactam. (3) Enterobacter cloacae P99 class C beta-lactamase in complex with biapenem.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] Louis Stokes Cleveland VA Medical Center(U.S.A.)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients.2017

    • Author(s)
      Papp-Wallace KM, Becka SA, Zeiser ET, Ohuchi N, Mojica MF, Gatta JA, Falleni M, Tosi D, Borghi E, Winkler ML, Wilson BM, LiPuma JJ, Nukaga M, Bonomo RA.
    • Journal Title

      ACS Infect Dis.

      Volume: 印刷中 Issue: 7 Pages: 502-511

    • DOI

      10.1021/acsinfecdis.7b00020

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] クラスCβ-ラクタマーゼー構造、反応機構、進化2015

    • Author(s)
      額賀路嘉
    • Journal Title

      臨床と微生物

      Volume: 42 Pages: 35-42

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] “Size matters”: Probing the Mechanisms of Inactivation of Class C beta-lactamases with Avibactam (AVI)2016

    • Author(s)
      M. Nukaga, S. Lefurgy, K. Papp-Wallace, RA Bonomo
    • Organizer
      Interscience Conference of Antimicrobial Agents and Chemotherapy 2016,Boston, MA
    • Place of Presentation
      Boston
    • Year and Date
      2016-06-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Size Matters”: Probing the Mechanisms of Inactivation of Class C β-Lactamases with Avibactam (AVI)2016

    • Author(s)
      M. Nukaga, S. T. Lefurgy, M. D. Barnes, K. M. Papp-Wallace and R. A. Bonomo
    • Organizer
      56th Interscience Conference of Antimicrobial Agents and Chemotherapy(ICAAC)
    • Place of Presentation
      Boston, MA, USA.
    • Year and Date
      2016-06-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exploring the Inactivation Mechanism by Avibactam (AVI) of an Inhibitor-Resistant Carbapenemase, PenA from Burkholderia multivorans (Bm)2015

    • Author(s)
      K. M. Papp-Wallace, J. A. Gatta, N. Ohuchi, M. L. Winkler, S. A. Becka, J. J. LiPuma, R. A. Bonomo, M. Nukaga
    • Organizer
      Interscience Conference of Antimicrobial Agents and Chemotherapy 2015,San Diego, CA
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2015-09-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Studies on the Inactivation of Enterobacter cloacae P99 Class C beta-Lactamase by Carbapenems: Doripenem, Panipenem, Imipenem and Biapenem2015

    • Author(s)
      M. Nukaga, N. Ohuchi, C. R. Bethel, R. A. Bonomo
    • Organizer
      Interscience Conference of Antimicrobial Agents and Chemotherapy 2015,San Diego, CA
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2015-09-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2018-03-22  

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