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L-proline as a nitrogen source increases the susceptibility of Saccharomyces cerevisiae S288c to fluconazole
C A Stella1, R Costanzo, H I Burgos
1Biochemistry Department, School of Medicine, Buenos Aires University, Argentina.
Abstract:
Fluconazole inhibition of Saccharomyces cerevisiae S288c growth was evaluated in media containing ammonia, L-proline or L-leucine as a nitrogen source. Growth inhibition by fluconazole was maximum when L-proline was used as a nitrogen source, while rhodamine 6G accumulation and fluconazole resistance were the highest when ammonia was the sole nitrogen source.
Insights
Fluconazole growth inhibition in Saccharomyces cerevisiae varies with nitrogen source. L-proline maximized inhibition, while ammonia led to the highest fluconazole resistance and rhodamine 6G accumulation.
Area of Science:
- Microbiology
- Mycology
- Biochemistry
Background:
- Saccharomyces cerevisiae is a model organism for studying fungal biology.
- Fluconazole is a widely used antifungal agent.
- Nitrogen availability can influence fungal growth and drug response.
Purpose of the Study:
- To investigate the impact of different nitrogen sources on fluconazole's antifungal activity.
- To determine how nitrogen availability affects fluconazole resistance and cellular accumulation.
Main Methods:
- Evaluating Saccharomyces cerevisiae S288c growth inhibition by fluconazole.
- Utilizing ammonia, L-proline, and L-leucine as sole nitrogen sources.
- Measuring rhodamine 6G accumulation as an indicator of drug efflux.
Main Results:
- Fluconazole exhibited maximum growth inhibition when L-proline was the nitrogen source.
- Ammonia as the sole nitrogen source resulted in the highest levels of rhodamine 6G accumulation.
- Ammonia also correlated with the highest fluconazole resistance in Saccharomyces cerevisiae.
Conclusions:
- The choice of nitrogen source significantly modulates fluconazole's efficacy and resistance mechanisms in Saccharomyces cerevisiae.
- L-proline enhances fluconazole's direct inhibitory effect on growth.
- Ammonia promotes efflux pump activity, leading to increased fluconazole resistance.