The yeast Candida albicans is an opportunistic human fungal pathogen and the cause of superficial and systemic
infections in immunocompromised patients. The classes of
antifungal agents most commonly used to treat
Candida infections are the
azoles,
polyenes, and
echinocandins. In the present study, we identified changes in C. albicans
protein abundance using two-dimensional
polyacrylamide gel electrophoresis and matrix-assisted
laser desorption ionization-time of flight mass spectroscopy following exposure to representatives of the
azole (
ketoconazole), polyene (
amphotericin B), and
echinocandin (
caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of
antifungal agents. We identified 39
proteins whose abundance changed in response to
ketoconazole exposure. Some of these
proteins are involved in
ergosterol biosynthesis and are associated with
azole resistance. Exposure to
amphotericin B altered the abundance of 43
proteins, including those associated with oxidative stress and osmotic tolerance. We identified 50
proteins whose abundance changed after exposure to
caspofungin, including
enzymes involved in cell wall biosynthesis and integrity, as well as the regulator of
beta-1,3-glucan synthase activity, Rho1p. Exposure to
caspofungin also increased the abundance of the
proteins involved in oxidative and osmotic stress. The common adaptive responses shared by all three
antifungal agents included
proteins involved in carbohydrate metabolism. Some of these antifungal-responsive
proteins may represent potential targets for the development of novel
therapeutics that could enhance the antifungal activities of these drugs.