Characterization of IMP-1, a major carbapenem resistance factor in bacteria

• Project/Area Number: 15H04868
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagoya University
• Principal Investigator: Arakawa Yoshichika 名古屋大学, 医学系研究科, 教授 (10212622)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Kouji 名古屋大学, 大学院医学系研究科, 准教授 (50425675) ; WACHINO Jun-ichi 名古屋大学, 大学院医学系研究科, 講師 (00535651)
• Research Collaborator: JIN Wanchun 名古屋大学, 大学院医学系研究科, 特任助教 ; ANUPRIYA Kumar 名古屋大学, 大学院医学系研究科, 特任助教 ; BANNO Hirotsugu 名古屋大学, 大学院医学系研究科 ; KITAOKA Kazuki 名古屋大学, 大学院医学系研究科 ; KANECHI Leo 名古屋大学, 大学院医学系研究科 ; KANAYAMA Takato 名古屋大学, 大学院医学系研究科
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 薬剤耐性菌 / IMP-1 / メタロベータラクタマーゼ / 阻害剤 / ベータラクタマーゼ

Outline of Final Research Achievements

Emerging of drug-resistant bacteria is a major clinical concern. Thus, it is essential to develop new antibiotics and agents to overcome the problem of drug-resistant bacteria. To respond to the aforementioned urgent and unmet needs, we have screened for metallo-beta-lactamase (MBL) inhibitor. MBL inhibitor can revive the efficacy of carbapenem antibiotics. We have screened 2107 small molecule compounds to identify IMP-1 inhibitor, IMP-1 is the dominant MBL in clinically isolated Enterobacteriaceae. Enzymatic and biological analyses revealed that 8 compounds would be candidates of IMP-1 inhibitor. These 8 compounds would be a great help to overcome carbapenem resistance caused by production of IMP-type MBL.

Research Products

• [Journal Article] Detection of <i>Escherichia coli</i> Producing CTX-M-1-Group Extended-Spectrum β-Lactamases from Pigs in Aichi Prefecture, Japan, between 2015 and 2016 (2018)
  • Author(s): Chihiro Norizuki, Kumiko Kawamura, Jun-ichi Wachino, Masahiro Suzuki, Noriyuki Nagano, Takaaki Kondo, Yoshichika Arakawa.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 71 Issue: 1 Pages: 33-38
  • DOI: 10.7883/yoken.JJID.2017.206
  • NAID: 130006317356
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access
• [Journal Article] Predominance of Serogroup 19 CC320/271 among Penicillin-Nonsusceptible <i>Streptococcus pneumoniae</i> Isolates after Introduction of the PCV7 Vaccine in Several Regions of Japan (2018)
  • Author(s): Mitsuru Oodate, Kouji Kimura, Hirotsugu Banno, Satoru Yokoyama, Wanchun Jin, Jun-ichi Wachino, Yoshinori Hasegawa, Yoshichika Arakawa
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 71 Issue: 1 Pages: 14-20
  • DOI: 10.7883/yoken.JJID.2017.236
  • NAID: 130006317355
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed
• [Journal Article] Recurrence of Escherichia coli meningitis in a preterm infant and co-infection of echovirus 18. (2017)
  • Author(s): Kentaro Kato, Hiroshi Mizumoto, Kousaku Matsubara, Atsuko Hata, Jun-ichi Wachino, Yoshichika Arakawa, and Daisuke Hata
  • Journal Title: IDCases Volume: 10 Pages: 135-137
  • DOI: 10.1016/j.idcr.2017.11.003
  • Peer Reviewed
• [Journal Article] Analysis of multidrug resistant group B streptococci with reduced penicillin susceptibility forming small, less hemolytic colonies. (2017)
  • Author(s): Hirotsugu Banno, Kouji Kimura , Yosuke Tanaka, Tsuyoshi Sekizuka, Makoto Kuroda, Wanchun Jin, Jun-ichi Wachino, Keiko Yamada, Keigo Shibayama, Yoshichika Arakawa
  • Journal Title: PLOS one Volume: 12(8) Issue: 8 Pages: e0183453-e0183453
  • DOI: 10.1371/journal.pone.0183453
  • Peer Reviewed
• [Journal Article] Structural Insights into the TLA-3 Extended-Spectrum β-Lactamase and Its Inhibition by Avibactam and OP0595 (2017)
  • Author(s): Wanchun Jin, Jun-ichi Wachino, Yoshihiro Yamaguchi, Kouji Kimura, Anupriya Kumar, Mototsugu Yamada, Akihiro Morinaka, Yoshiaki Sakamaki, Minoru Yonezawa, Hiromasa Kurosaki and Yoshichika Arakawa
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 61(10)
  • Peer Reviewed
• [Presentation] Avibactam-, OP0595-TLA-3 ベータラクタマーゼ複合体のX線結晶構造解析 (2018)
  • Author(s): Wanchun Jin, 和知野純一, 木村幸司, 荒川宜親
  • Organizer: 第91回日本細菌学会総会
• [Presentation] Carbapenem Resistance due to Amino Acid Insertion in Penicillin-Binding Protein of 3 of beta-Lactamase-Negative Ampicillin-Resistant Haemophilus Influenzae (2017)
  • Author(s): Kazuki Kitaoka, Kouji Kimura, Hirotsugu Banno, Wanchun Jin, Jun-ichi Wachino, and Yoshichika Arakawa
  • Organizer: 第54回日本細菌学会中部支部総会
• [Presentation] Characterization of Group B Streptococci with Reduced Penicillin Susceptibility Forming Small Less-beta-Hemolytic Colonies on Sheep Blood Agar (2017)
  • Author(s): 坂野弘嗣、木村幸司、田中洋輔、関塚剛史、黒田誠、和知野純一、山田景子、柴山恵吾、荒川宜親
  • Organizer: 第54回日本細菌学会中部支部総会
• [Presentation] メタロベータラクタマーゼVIM-2の精製と阻害剤探索 (2017)
  • Author(s): 仲崇天、和知野純一、木村幸司、荒川宜親
  • Organizer: 第54回日本細菌学会中部支部総会