Molecular basis research on the mechanism of action of aminoglycoside resistance inhibitors of multidrug-resistant Pseudomonas aeruginosa

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Aichi Gakuin University
• Principal Investigator: Morita Yuji 愛知学院大学, 薬学部, 准教授 (00454322)
• Co-Investigator(Renkei-kenkyūsha): NISHINO Kunihiko 大阪大学, 産業科学研究所, 教授 ; YASUIKE Shuji 愛知学院大学, 薬学部, 教授 (10230210) ; MATSUMURA Mio 愛知学院大学, 薬学部, 助教 (20712037) ; KAWASAKI Tatsuya 愛知学院大学, 薬学部, 助教 (70722073)
• Research Collaborator: KAWAMURA Yoshiaki 愛知学院大学, 薬学部, 教授 (80262757) ; TOMIDA Junko 愛知学院大学, 薬学部, 講師 (10454323) ; KOJIMA Yuki ; KUSU Akane ; KOTANI Kenta ; FUKAYA Shiori
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 多剤耐性緑膿菌 / 多剤排出系阻害 / ベルベリン

Outline of Final Research Achievements

We analyzed the mechanism of action of berberine, which inhibits aminoglycoside resistance of multidrug - resistant Pseudomonas aeruginosa in a manner dependent on RND - type multidrug efflux system MexXY, and further berberine derivative which enhances the action of berberine was constructed. We suggested that 1) berberine seems a substrate of the MexXY pump, 2) berberine acts synergistically with aminoglycoside depending on the MexXY system, 3) the putative binding site of berberine to MexY is close to aminoglycoside. Berberine derivatives (X and Y) inhibited amikacin resistance of multidrug resistant Pseudomonas aeruginosa at concentrations as low as 4 to 16 times lower than berberine. The MexXY inhibitory activity of compound X was about the same as that of berberine, and the MexXY system inhibitory activity of compound Y was about 16 times that of berberine.

Free Research Field

微生物薬品科学