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Development of phenotypic resistance to direct lethal miconazole action by Candida albicans entering stationary phase
1General Medical Research Service, Veterans Administration Medical Center, Minneapolis, MN 55417.
Abstract:
In the late logarithmic or very early stationary phase of the growth cycle, yeast cells of Candida albicans undergo a shift from susceptibility to resistance to the direct lethal action of miconazole. Regulation of this phenotypic shift was examined. Experiments based on viable count determinations and the construction of time-kill curves showed that reestablishment of resistance is independent of both pH and the attainment of some critical viable cell density. However, it was found that development of resistance requires the continued availability of an appropriate energy source toward the end of exponential growth.
Insights
Candida albicans yeast cells develop resistance to miconazole as they transition to later growth phases. This resistance requires an available energy source, independent of cell density or pH.
Area of Science:
- Mycology
- Antifungal Resistance
- Cellular Physiology
Background:
- Candida albicans, a common fungal pathogen, exhibits dynamic changes in drug susceptibility during its growth cycle.
- Understanding the mechanisms regulating antifungal resistance is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the regulatory factors governing the shift in Candida albicans from miconazole susceptibility to resistance.
- To determine the conditions necessary for the development of antifungal resistance in yeast cells.
Main Methods:
- Utilizing viable count determinations to assess fungal survival.
- Constructing time-kill curves to monitor the lethal effects of miconazole over time.
- Manipulating environmental factors such as pH and energy source availability during yeast growth.
Main Results:
- The development of miconazole resistance in Candida albicans is not dependent on pH or a specific cell density.
- Continued availability of an energy source is essential for the yeast to acquire resistance.
- This phenotypic shift occurs during the late logarithmic or early stationary growth phases.
Conclusions:
- The energy-dependent acquisition of miconazole resistance in Candida albicans is a critical factor in its survival.
- This finding highlights the importance of metabolic state in antifungal drug response.
- Further research into energy metabolism could reveal new targets for antifungal therapies.