Titre
Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Sanglard, D.
Auteure/Auteur
Ischer, F.
Auteure/Auteur
Monod, M.
Auteure/Auteur
Bille, J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0066-4804
Statut éditorial
Publié
Date de publication
1996-10
Volume
40
Numéro
10
Première page
2300
Dernière page/numéro d’article
5
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
Some Candida albicans isolates from AIDS patients with oropharyngeal candidiasis are becoming resistant to the azole antifungal agent fluconazole after prolonged treatment with this compound. Most of the C. albicans isolates resistant to fluconazole fail to accumulate this antifungal agent, and this has been considered a cause of resistance. This phenomenon was shown to be linked to an increase in the amounts of mRNA of a C. albicans ABC (ATP-binding cassette) transporter gene called CDR1 and of a gene conferring benomyl resistance (BENr), the product of which belongs to the class of major facilitator multidrug efflux transporters (D. Sanglard, K. Kuchler, F. Ischer, J. L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother. 39:2378-2386, 1995). To analyze the roles of these multidrug transporters in the efflux of azole antifungal agents, we constructed C. albicans mutants with single and double deletion mutations of the corresponding genes. The mutants were tested for their susceptibilities to these antifungal agents. Our results indicated that the delta cdr1 C. albicans mutant was hypersusceptible to the azole derivatives fluconazole, itraconazole, and ketoconazole, thus showing that the ABC transporter Cdr1 can use these compounds as substrates. The delta cdr1 mutant was also hypersusceptible to other antifungal agents (terbinafine and amorolfine) and to different metabolic inhibitors (cycloheximide, brefeldin A, and fluphenazine). The same mutant was slightly more susceptible than the wild type to nocodazole, cerulenin, and crystal violet but not to amphotericin B, nikkomycin Z, flucytosine, or pradimicin. In contrast, the delta ben mutant was rendered more susceptible only to the mutagen 4-nitroquinoline-N-oxide. However, this mutation increased the susceptibilities of the cells to cycloheximide and cerulenin when the mutation was constructed in a delta cdr1 background. The assay used in the present study could be implemented with new antifungal agents and is a powerful tool for assigning these substances as putative substrates of multidrug transporters.
Sujets
PID Serval
serval:BIB_9C1896458842
PMID
Date de création
2008-01-25T15:47:14.636Z
Date de création dans IRIS
2025-05-21T01:51:50Z