Analyses of mechanism of action of a quorum sensing inhibitor by using real-time imaging system

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Okayama Gakuin University (2015-2016); Okayama University (2013-2014)
• Principal Investigator: KARIYAMA REIKO 岡山学院大学, 人間生活学部, 准教授 (40112148)
• Co-Investigator(Renkei-kenkyūsha): KUMON Hiromi 岡山大学, 医歯薬学総合研究科, 特命教授 (30144760) ; Suga Hiroaki 東京大学, 理学系研究科, 教授 (00361668)
• Research Collaborator: HORI Kenji ; MITSUHATA Ritsuko
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 難治性感染症 / 緑膿菌 / 治療 / クオラムセンシング阻害剤 / オートインデューサーアナログ / 抗菌薬抵抗性 / リード化合物 / リアルタイムイメージング

Outline of Final Research Achievements

In order to advance the development of a new type of drug for the treatment of infectious diseases, we herein investigated the effects of a newly synthesized analogue of the Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 (autoinducer analogue) on antibiotic tolerance in P. aeruginosa. Newly developed in vivo and in vitro assays showed that AIA-1 alone did not exert any bactericidal effects and also did not affect the MICs of antibiotics. However, the combined use of AIA-1 and antibiotics exerted markedly stronger therapeutic effects against mouse infection than antibiotics alone. The new compound, AIA-1 did not alter the antibiotic susceptibility of P. aeruginosa by itself; however, its addition enhanced the antibacterial activity of antibiotics. AIA-1 reduced the antibiotic tolerance of P. aeruginosa by suppressing rpoS gene expression. In conclusion, AIA-1 may be a potent drug for clinical treatment of infections caused by antibiotic-resistant bacteria.

Free Research Field

医歯薬学