Development of novel antifungal chemotherapy based on vacuole-disruptive activity.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Osaka City University
• Principal Investigator: OGITA Akira 大阪市立大学, 都市健康・スポーツ研究センター, 准教授 (00244624)
• Co-Investigator(Renkei-kenkyūsha): FUJITA Ken-ichi 大阪市立大学大学院, 理学研究科, 准教授 (10285281) ; TANAKA Toshio 大阪市立大学大学院, 理学研究科, 教授 (10137185) ; SHIMIZU Takashi 山口大学, 農学部, 准教授 (40320155)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 液胞破壊作用

Outline of Final Research Achievements

To attempt realization of a novel antifungal chemotherapy based on selective fungal vacuole-disruptive activities using amphotericin B, exploring novel amplifier factors and elucidating their action mechanism were performed. These studies showed that N-methyl-N"-dodecylguanidine, a synthetic analogue of the alkyl side chain of niphimycin, would be a candidate as an enhancer of activities of vacuole targeting antifungal antibiotics, in addition to allicin, an allyl sulfur compound from garlic, and partly revealed its mode of action.
Our results obtained with analyses of the mode of action suggested that the presence of ergosterol as a component in membranes and progression of autophagy induced execution of vacuole-disruption. We additionally proposed a practical approach to realize an antifungal chemotherapy via selective vacuole-disruptive activities.

Free Research Field

生体分子機能学