New approaches against multi-drug resistant Pseudomonas aeruginosa infection using RNA interfering

• Project/Area Number: 23591479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Oita University
• Principal Investigator: HIRAMATSU Kazufumi 大分大学, 医学部, 准教授 (80301381)
• Co-Investigator(Kenkyū-buntansha): KADOTA Jun-ichi 大分大学, 医学部, 教授 (50233838)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 緑膿菌 / siRNA / IMP-1 / 薬剤耐性

Outline of Final Research Achievements

IMP-1 producing multi-drug resistant Pseudomonas aeruginosa (MDRP)-infection is critical problem because there is no effective agents without colistin. RNA interfering (RNAi) has been known to suppress the targeted protein experession in eucaryocytes. In order to suppress IMP-1 production from MDRP, we synthesized short interfering RNAs (siRNAs) to IMP-1 and evaluated effect of those siRNA against production of IMP-1. Although non-labeled siRNA was not incorporated to P. aeruginosa sufficiently, cholesterol-modified siRNA entered into the cells. When IMP-1 producing P. aeruginosa was incubated with cholesterol modified siRNA and ceftazidime, the bacterial cell counts increased. However when 10 types of siRNAs and ceftazidime incubated with bacteria simultaneously, cell counts decreased to one-tenth compared with control. These results suggested a possibility of RNAi against treatment of IMP-1 producing MDRP infections.