The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering anti-fungal agents with new mechanisms of action and on optimizing the use of existing agents. In this context, interest in the polyene group of anti-fungals has recently been renewed, since they are known to be effective against a broad spectrum of fungal pathogens that only rarely develop a resistance to them. In the past 10 years considerable efforts have been made to improve their efficacy and, simultaneously, to reduce their toxicity. Knowledge about the basic mechanisms of their action will be of crucial importance to further optimizing their use. The mechanisms of polyene action at the membrane level are reviewed here, focusing primarily on their pore-forming activity and on the resulting osmotic responses of artificial lipid vesicles and different eukaryotic cells.

The cell volume changes induced by hypotonic electrolyte and sucrose solutions were studied in Chinese-hamster-ovary epithelial cells. The effects in the solutions with osmolarities between 32 and 315 mosM/L and distilled water were analyzed using bright-field and fluorescence confocal microscopy. The changes of the cell volume, accompanied by the detachment of cells, the formation of blebs, and the occurrence of almost spherical vesicle-like cells (“cell-vesicles”), showed significant differences in the long-time responses of the cells in the electrolyte solutions compared with the sucrose-containing solutions. A theoretical model based on different permeabilities of ions and sucrose molecules and on the action of Na⁺/K⁺-ATPase pumps is applied. It is consistent with the observed temporal behavior of the cells’ volume and the occurrence of tension-induced membrane ruptures and explains lower long-time responses of the cells in the sucrose solutions.