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Published on: September 16, 2022
The influence of ketoconazole on the activity of asparagine protease produced by Candida strains
Piotr Kurnatowski1, Arkadiusz Grabek
1Department of Biology and Medical Parasitology, Medical University of L6di, Hallera 1, Lódź, Poland.
Abstract:
The investigations concerning the activity of antimycotic drugs on pathogenic fungi, revealed a decrease of sensitivity of fungi, especially of the Candida species. In other investigations we have stated that strains isolated from patients have other than standard enzymatic activity. So it seems to be interesting to have evaluated the model for analysis in vitro the influence of antimycotic drug for egzoenzyme of fungi. The aims of the study were: 1. estimation of the influence in vitro ketoconazole, which was added everyday for 3 weeks on curves of activity of the drug, on strains isolated from patients; 2. estimation of asparagine protease activity on strains before, during and after the added drug to the culture. During the study we evaluated the model in vitro to obtain strains with lower sensitivity for a antimycotic drug. Everyday during a 3 week period we added to the culture ketoconazole in the concentration of about 2, 4 and 6 times higher than the minimal inhibitory concentration (MIC). Before, 1, 2 and 3 weeks after we investigated the activity of asparaginee protease. We obtained the following results: 1. Ketoconazole added to the culture of Candida strains during 3 weeks had influenced the response curves, which was observed as statistical significant changes between MIC values. 2. Ketoconazole after 1 week of administration decreased and after 2 and 3 weeks increased of asparagine protease activity.
Insights
Antimycotic drug resistance is increasing in pathogenic fungi like Candida. This study shows ketoconazole alters fungal sensitivity and asparagine protease activity over time, offering insights into drug resistance mechanisms.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
Background:
- Pathogenic fungi, particularly Candida species, exhibit decreasing sensitivity to antimycotic drugs.
- Fungal strains from patients display non-standard enzymatic activity, necessitating further investigation.
- Understanding the in vitro effects of antimycotic drugs on fungal exoenzymes is crucial.
Purpose of the Study:
- To evaluate the in vitro influence of ketoconazole on the drug sensitivity of patient-isolated fungal strains over three weeks.
- To assess the changes in asparagine protease activity in fungal strains exposed to ketoconazole.
- To develop a model for analyzing the development of reduced antimycotic drug sensitivity in vitro.
Main Methods:
- Fungal cultures were exposed daily to ketoconazole at 2, 4, and 6 times the minimal inhibitory concentration (MIC) for three weeks.
- Asparagine protease activity was measured before, during (1, 2, and 3 weeks), and after ketoconazole administration.
- Statistical analysis was performed to determine significant changes in drug activity and enzyme levels.
Main Results:
- Ketoconazole treatment over three weeks significantly altered the drug response curves of Candida strains, indicated by changes in MIC values.
- Asparagine protease activity decreased after one week of ketoconazole administration and increased after two and three weeks.
Conclusions:
- Ketoconazole exposure in vitro can modify the sensitivity of Candida strains to antimycotic drugs.
- Changes in asparagine protease activity correlate with ketoconazole administration, suggesting a role in drug resistance.
- The study provides a model for investigating the in vitro development of reduced fungal sensitivity to antimycotic agents.
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