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Target substances of some antifungal agents in the cell membrane

Copiamycin, an antifungal antibiotic, exhibits antimicrobial activity against a few bacteria in addition to a wide variety of fungi. The methanol extract of Sarcina lutea, one of the most susceptible bacteria, was found to reverse the antimicrobial activity of copiamycin. The reversing activity was associated with the phospholipid fraction of the bacteria. The S. lutea phospholipids also reversed the activities of azalomycin F and miconazole, but not that of clotrimazole. The effects of authentic phospholipids and fatty acids were also investigated. As the antimicrobial activities of copiamycin and azalomycin F were most strongly reversed in the same manner by phospholipids with unsaturated fatty acids and basic hydrophilic groups, the sites on the cell membrane sensitive to both antibiotics are assumed to be identical. On the other hand, the activity of miconazole was affected by different phospholipids from those which affected these two antifungal antibiotics, and the activity of clotrimazole was not affected by any of the phospholipids and fatty acids. It was postulated that the sites on the cell membrane sensitive to miconazole and clotrimazole are different from those sensitive to copiamycin and azalomycin F.