Titre du document / Document title

Drug induced proteome changes in Candida albicans: Comparison of the effect of β(1,3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole

Auteur(s) / Author(s)

BRUNEAU Jean-Michel ⁽¹⁾ ; MAILLET Isabelle ⁽¹⁾ ; TAGAT Eric ⁽¹⁾ ; LEGRAND Raymond ⁽²⁾ ; SUPATTO Francoise ⁽²⁾ ; FUDALI Claude ⁽²⁾ ; LE CAER Jean-Pierre ⁽³⁾ ; LABAS Valérie ⁽³⁾ ; LECAQUE Dominique ⁽⁴⁾ ; HODASON John ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Infections Disease Group, Aventis Pharma, Romainville, FRANCE
⁽²⁾ Functional Genomics, Aventis Pharma, Romainville, FRANCE
⁽³⁾ Ecole Supérieure de Physique et de Chimie Industrielles, Paris, FRANCE
⁽⁴⁾ Histology Department, Aventis Pharma, Romainville, FRANCE

Résumé / Abstract

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 a 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.

Revue / Journal Title

Proteomics   ISSN 1615-9853 

Source / Source

2003, vol. 3, n^o3, pp. 325-336 [12 page(s) (article)] (28 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley-VCH, Weinheim, ALLEMAGNE  (2001) (Revue)

Mots-clés anglais / English Keywords

Yeast ; Thallophyta ; Fungi ; Fungi Imperfecti ; Triazole derivatives ; Itraconazole ; Fluconazole ; Mechanism of action ; Antifungal agent ; Protein ; Proteomics ; Candida albicans ;

Mots-clés français / French Keywords

Levure ; Thallophyta ; Fungi ; Fungi Imperfecti ; Echinochandine dérivé ; Triazole dérivé ; Itraconazole ; Fluconazole ; Mécanisme action ; Antifongique ; Protéine ; Protéomique ; Candida albicans ;

Mots-clés espagnols / Spanish Keywords

Levadura ; Thallophyta ; Fungi ; Fungi Imperfecti ; Triazol derivado ; Itraconazol ; Fluconazol ; Mecanismo acción ; Antifúngico ; Proteína ; Proteómica ; Candida albicans ;

Localisation / Location

INIST-CNRS, Cote INIST : 27206, 35400011080976.0110