Analysis of bacterial drug efflux pumps and development of inhibitors to avoid pandemics caused by resistant bacteria

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K14902
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Osaka University
• Principal Investigator: Yamasaki Seiji 大阪大学, 高等共創研究院, 准教授 (70757301)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 耐性菌 / 感染症 / 排出ポンプ / 細菌 / 抗生物質 / 抗菌薬 / 薬剤耐性 / 多剤耐性

Outline of Final Research Achievements

The binding position inside the efflux pump of lauryl maltose neopentyl glycol (LMNG, MW 1,005), the bulkiest compound to date, has been clarified. The detailed mutant analysis showed that the efflux pump does not determine the binding pocket it recognizes based on the simple molecular weight and bulkiness of the compound, but uses two different binding pockets depending on the individual properties and structure of the compound. The clarification of the details inside the efflux pump, especially the substrate binding site, is expected to lead to the development of effective new inhibitors of the efflux pump.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

世界中の医療従事者が直面している薬剤耐性菌感染症の克服、および大規模な耐性菌パンデミックの回避に向け、耐性化に大きく寄与している細菌の薬剤排出ポンプとその発現制御因子に着目した分子標的創薬の実現に大きく寄与することができる。