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Drug induced proteome changes in Candida albicans: Comparison of the effect of β(1,3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole
Author(s) -
Bruneau JeanMichel,
Maillet Isabelle,
Tagat Eric,
Legrand Raymond,
Supatto Françoise,
Fudali Claude,
Caer JeanPierre Le,
Labas Valérie,
Lecaque Dominique,
Hodgson John
Publication year - 2003
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200390046
Subject(s) - candida albicans , itraconazole , fluconazole , echinocandin , azole , echinocandins , corpus albicans , lanosterol , microbiology and biotechnology , proteome , antifungal drug , ketoconazole , biology , ergosterol , fungal protein , systemic candidiasis , pharmacology , yeast , biochemistry , antifungal , saccharomyces cerevisiae , sterol , cholesterol , caspofungin
The dimorphic fungus Candida albicans is an opportunistic human pathogen. Candidiasis is usually treated with azole antifungal agents. However clinical treatments may fail due to the appearance of resistance to this class of antifungal agents in Candida. Echinocandin derivatives are an alternative for the treatment of these fungal infections and are active against azole resistant isolates of C. albicans. Azoles inhibit the lanosterol 14 α demethylase which is a key enzyme in the synthesis of ergosterol. In contrast, the echinocandin class of antibiotics inhibit noncompetitively β‐(1,3)‐ D ‐glucan synthesis in vitro. We have investigated the impact of mulundocandin on the proteome of C. albicans and compared it to those of a mulundocandin derivative, as well as to two azoles of different structure, fluconazole and itraconazole. The changes in gene expression underlying the antifungal responses were analyzed by comparative 2‐D PAGE. Dose dependant responses were kinetically studied on C. albicans grown at 25°C (yeast form) in synthetic dextrose medium. This study shows that antifungals with a common mechanism of action lead to comparable effects at the proteome level and that a proteomics approach can be used to distinguish different antifungals, with the promise to become a useful tool to study drugs of unknown mechanism of action.