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Published on: February 14, 2018
Sensitivity of Trichophyton mentagrophytes strains to three imidazole drugs
1Department of Medical Biology, Medical Faculty, Palacký University, Olomouc, Czechoslovakia.
Abstract:
A total of 84 strains of the dermatophyte Trichophyton mentagrophytes were studied for their sensitivity to ketoconazole, miconazole, and clotrimazole. Minimal inhibitory concentration was used for determination of sensitivity. Variability in the sensitivity of strains to the tested imidazole drugs ranged within one to two orders (10(-2)-10(0) micrograms/ml). By means of UV radiation ketoconazole-resistant mutants were prepared: their frequency was 1.3 x 10(-7) mutants per spore and nucleus. A repeated exposition to the mutagen lead to increased resistance. Correlation was also studied between inhibitory effect of ketoconazole on mycelial growth and that on ergosterol biosynthesis but no significant results were obtained.
Insights
This study investigated the antifungal drug sensitivity of Trichophyton mentagrophytes strains. Ketoconazole-resistant mutants were successfully generated using UV radiation, demonstrating increased resistance upon repeated exposure.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
Background:
- Dermatophytes like Trichophyton mentagrophytes cause superficial fungal infections.
- Imidazole antifungal drugs are commonly used for treatment.
- Understanding drug resistance mechanisms is crucial for effective therapy.
Purpose of the Study:
- To assess the sensitivity of Trichophyton mentagrophytes strains to ketoconazole, miconazole, and clotrimazole.
- To investigate the generation and characteristics of ketoconazole-resistant mutants.
- To explore the correlation between ketoconazole's effect on fungal growth and ergosterol biosynthesis.
Main Methods:
- Minimal Inhibitory Concentration (MIC) assay to determine drug sensitivity.
- Induction of drug-resistant mutants using UV radiation.
- Assessment of ergosterol biosynthesis inhibition.
Main Results:
- Variability in imidazole drug sensitivity observed across strains (10^-2-10^0 µg/ml).
- Ketoconazole-resistant mutants were generated with a frequency of 1.3 x 10^-7 per spore/nucleus.
- Repeated UV exposure led to increased ketoconazole resistance.
- No significant correlation found between ketoconazole's effect on mycelial growth and ergosterol biosynthesis.
Conclusions:
- Trichophyton mentagrophytes exhibits variable sensitivity to common imidazole antifungals.
- UV radiation is effective in generating ketoconazole-resistant mutants, highlighting potential resistance pathways.
- Further research is needed to elucidate the mechanisms underlying ketoconazole resistance and its impact on ergosterol biosynthesis.
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