Investigating Universal Binding Mechanisms of Drug Efflux Pumps to Develop Broad-Spectrum Inhibitors and Overcome Multidrug-Resistant Bacterial Infections

• Project/Area Number: 25K10343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: The University of Osaka
• Principal Investigator: ZWAMA MARTIJN 大阪大学, 産業科学研究所, 特任准教授(常勤) (40827052)
• Project Period (FY): 2025-04-01 – 2028-03-31
• Project Status: Granted (Fiscal Year 2025)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2027: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2026: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2025: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Inhibitor / RND / Multidrug resistance / Pathogens / MDR

Outline of Research at the Start

This proposal addresses a key question in combating MultiDrug Resistance (MDR) in bacteria: Can a universal binding mechanism across multidrug efflux pumps be targeted to overcome antibiotic resistance? Preliminary data suggests efflux pumps from different species share conserved interactions with outer membrane proteins (OMPs), like E. coli TolC. The goal is to explore this universal mechanism, leading to broad-spectrum efflux pump inhibitors (EPIs). This innovative approach focuses on cross-species conservation to target shared interactions, offering a new path to combat MDR globally.