Titre
A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Calabrese, D.
Auteure/Auteur
Bille, J.
Auteure/Auteur
Sanglard, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1350-0872
Statut éditorial
Publié
Date de publication
2000-11
Volume
146 ( Pt 11)
Première page
2743
Dernière page/numéro d’article
54
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
Azole resistance in Candida albicans can be mediated by several resistance mechanisms. Among these, alterations of the azole target enzyme and the overexpression of multidrug efflux transporter genes are the most frequent. To identify additional putative azole resistance genes in C. albicans, a genomic library from this organism was screened for complementation of fluconazole hypersusceptibility in Saccharomyces cerevisiae YKKB-13 lacking the ABC (ATP-binding cassette) transporter gene PDR5. Among the C. albicans genes obtained, a new gene was isolated and named FLU1 (fluconazole resistance). The deduced amino acid sequence of FLU1 showed similarity to CaMDR1 (formerly BEN(r)), a member of the major facilitator superfamily of multidrug efflux transporters. The expression of FLU1 in YKKB-13 mediated not only resistance to fluconazole but also to cycloheximide among the different drugs tested. The disruption of FLU1 in C. albicans had only a slight effect on fluconazole susceptibility; however, it resulted in hypersusceptibility to mycophenolic acid, thus suggesting that this compound could be a substrate for the protein encoded by FLU1. Disruption of FLU1 in a background of C. albicans mutants with deletions in several multidrug efflux transporter genes, including CDR1, CDR2 and CaMDR1, resulted in enhanced susceptibility to several azole derivatives. FLU1 expression did not vary significantly between several pairs of azole-susceptible and azole-resistant C. albicans clinical isolates. Therefore, FLU1 seems not to be required for the development of azole resistance in clinical isolates.
Sujets
PID Serval
serval:BIB_05CE241EEAA4
PMID
Date de création
2008-01-25T13:40:15.724Z
Date de création dans IRIS
2025-05-20T18:01:01Z