Development of antipathogenic agents targeting quorum sensing of Gram-positive bacteria

2014 Fiscal Year Final Research Report

• Project/Area Number: 24380050
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied microbiology
• Research Institution: Kyushu University
• Principal Investigator: NAKAYAMA Jiro 九州大学, (連合)農学研究科(研究院), 准教授 (40217930)
• Co-Investigator(Kenkyū-buntansha): NAGATA Koji 東京大学, 大学院農学生命科学研究科, 准教授 (30280788) ; IGARASHI Yasuhiro 富山県立大学, 工学部, 教授 (20285159) ; SUZUKI Takashi 愛媛大学, 医学部附属病院, 講師 (70398048) ; SHIMIZU Tohru 金沢大学, 医学系, 教授 (80235655) ; OHTANI Kaori 金沢大学, 医学系, 講師 (30377410)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: クオラムセンシング / グラム陽性細菌 / 日和見感染 / 抗感染症剤 / ペプチドデザイン / 阻害剤開発 / クォルモン / アンタゴニスト

Outline of Final Research Achievements

Quorum sensing mediated by cyclic peptide as an autoinducer (AIP) commonly controls the expression of virulence in pathogenic Gram-positive bacteria such as staphylococci, enterococci and clostridia. In this study, we performed screening and drug design of quorum sensing inhibitors (QSI). Consequently, we found that a number of cyclic peptides of microbial secondary metabolites, e.g., WS9326A and Avellanin C, showed antagonistic activity against AIP at micromolar concentrations and attenuated virulences of Gram-positive pathogens. Further, we succeeded in designing of QSI peptides based on the structure of AIP of Clostridium perfringens, which attenuated the expression of theta toxin gene at submicromolar concentrations

Free Research Field

分子微生物学・生物有機化学