The effect of ketoconazole (KK) on chosen biochemical indexes was studied in three mutants of dermatophyte Microsporum gypseum (MG-155 wild strain) resistant to KK. Fungistatic concentration of KK added to liquid cultivate medium increases significantly ergosterol pool and nonsignificantly demethylation activity, potassium content, cAMP release in three days old mycelium of mutants when compared to the cultivation without KK. On the contrary, there is a significant suppression of ergosterol level and demethylation activity followed by highly significant increasing of potassium content and cAMP release in the case of wild strain MG-155.
The presented study deals with the properties of two wild strains of dermatophyte Microsporum gypseum and of eleven mutants resistant to ketoconazole. The growth rate of spontaneous mutants is greater than that of the wild strain, the group of UV-induced mutants manifests in general lower growth rate. The resistance level varies in the interval 1.1-1.6 (spontaneous mutants), resp. 2.7-5.5 (UV-induced mutants). The phenomenon of cross-resistance to other imidazole drugs (miconazole, clotrimazole) has been observed in mutants. There is further given the characteristic of ergosterol synthesis influence by the three used antifungal drugs. The data obtained are discussed from the point of view of possible biochemical processes resulting in the formation of resistance to ketoconazole.
The ketoconazole-resistant mutants were isolated from four strains of the dermatophyte Microsporum gypseum. The frequency of spontaneous mutants ranged within 10(-8) to 10(-9) (per spore and nucleus). The method was established for obtaining the spontaneous mutants manifested as the faster growing sectors. By means of mutagenic effect of UV radiation, the frequency of mutants increased by one order. The method used for determination of ergosterol the biosynthesis of which could be associated with the mechanism of resistance to ketoconazole is described and evaluated.
