Development of antibacterial auxiliary agents targeted for metallo-beta-lactamases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Nagoya University
• Principal Investigator: Wachino Jun-ichi 名古屋大学, 医学系研究科, 講師 (00535651)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: メタロベータラクタマーゼ / 阻害剤

Outline of Final Research Achievements

We developed here novel metallo-beta-lactamase inhibitors. Our inhibitors were able to suppress the enzymatic activities of subclass B1 metallo-beta-lactamases such as IMP-type, NDM-type, and VIM-type, which are dominant metallo-beta-lactamases in the world. In addition, our inhibitors could revive the in vitro carbapenem activity against metallo-beta-lactamase producing pathogenic bacteria. Combination therapy with carbapenem and inhibitors successfully cured mice infected with metallo-beta-lactamase producing pathogenic bacteria. Our inhibitors would provide a considerable benefit to patients receiving treatment for lethal infectious diseases caused by metallo-beta-lactamase producing pathogenic bacteria.

Free Research Field

薬剤耐性菌

Academic Significance and Societal Importance of the Research Achievements

メタロベータラクタマーゼ産生菌に対する新たな治療法の開発が喫緊の課題となっている。しかし、現在のところ、メタロベータラクタマーゼを標的にした阻害剤が開発・上市された例はない。本研究により開発したメタロベータラクタマーゼ阻害剤は強力で、しかも安全性も高いことから、将来、メタロベータラクタマーゼ産生菌感染症の治療薬として役立つ可能性がある。