Morphological Aspects of Antifungal Action

Abstract

To learn the cellular consequence of antifungal action of azoles and two other types of currently available ergosterol biosynthesis inhibiting antifungals (EBIA), terbinafine and amorolfine, the morphological changes induced by fungistatic concentrations of these drugs were examined electron microscopically using growing hyphae of Trichophyton mentagrophytes and yeast-form cells of Candida albicans, as well as reverting protoplasts of C. albicans “ as the test organisms. All of these EBIA seemed to have a common morphological effect on both hyphal (T. mentagrophytes) and yeast-form (C. albicans) cells. The treatment of these fungi with any test drug induced intracellular and, more frequently, intra-cell wall deposition of electrondense vesicles, presumably resulting from degeneration of cell membanes primarily caused by inhibition of ergosterol biosynthesis. However, even more prominent were the morphological changes involving the cell wall. Characteristic of these changes were formation of fragile and deteriorated walls and aberrant thickening of cell wall at specific sites, particularly apical walls and septal walls, with the resultant blockage of hyphal elongation or proliferation of yeast-form cells. This adverse effect of azoles and other types of EBIA on the morphogenesis of fungal cell walls was studied in more detail in C. albicans protoplasts which reverted to osmotically stable cells. The experimental results provided evidence suggesting that all of these antifungals impair coordinated synthesis and/or assembly of glucans, chitin and other fungal wallconstituting materials.