Synergistic Combination of Direct Plasma Membrane Damage and Oxidative Stress as a Cause of Antifungal Activity of Polyol Macrolide Antibiotic Niphimycin

概要

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The polyol macrolide niphimycin (NM) exhibited fungicidal activity against Saccharomyces cere-visiae cells accompanying the leakage of cytoplasmic components including nucleotide-like materials in addition to K^+ at 10 μM or above. Such a dynamic change in the plasma membrane was observed upon treatment of cells with H_2O_2 but not with the polyene macrolide antibiotic amphotericin B (AmB). The NM-induced cell death could be prevented by the exogenous addition of phosphatidylcholine (PC) whereas such a protective effect was only weakly observed with ergosterol, the molecular target of AmB. NM-treated cells were further characterized with a dramatic loss of glutathione even at a dose of 5 μM or less, representing NM-triggered metabolic conversion of the antioxidant molecule. NM-treatment indeed accelerated the cellular production of reactive oxygen species (ROS) such as H_2O_2 detectable with a specific fluorescent probe in a dose-dependent manner. These results suggested a synergistic combination of direct plasma membrane damage and oxidative stress as a cause of antifungal activity of NM against S. cerevisiae.
社団法人日本生物工学会の論文
2002-09-25