Ultrastructure of Saccharomyces cerevisiae Treated with Econazole

The ultrastructural bases for the fungicidal action of a membrane-active antifungal agent econazole on Saccharomyces cerevisiae were explored by a combination of freeze-fracture and thin-sectioning electron microscopical techniques. Studies with the freeze-fracture method demonstrated that econazole caused profound structural alterations in both fracture faces, particularly the PF face, of the cell membrane and were characterized by a decrease in compactness of intramembranous particles, emergence of large smooth areas encircling particle islands, and the formation of depressions over the entire surface. Cross-fractured specimens of the econazole-treated cells exhibited marked changes of contour and texture of the boundary membrane of cytoplasmic organelles such as mitochondria and nucleus. These observations were well confirmed by studies with the thin-sectioning method showing the cell membrane and other membranous structures in profile. The results of the present electron microscopical studies appear to meet the criteria based on previous biochemical studies that a fungicidal level of econazole severely damages fungal membranes through interaction with membrane phospholipids.