Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents

Détails

ID Serval
serval:BIB_C7F8767C7190
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Sanglard  D., Ischer  F., Parkinson  T., Falconer  D., Bille  J.
ISSN
0066-4804 (Print)
Statut éditorial
Publié
Date de publication
08/2003
Volume
47
Numéro
8
Pages
2404-12
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Résumé
The role of sterol mutations in the resistance of Candida albicans to antifungal agents has not been thoroughly investigated. Previous work reported that clinical C. albicans strains resistant to both azole antifungals and amphotericin B were defective in ERG3, a gene encoding sterol Delta(5,6)-desaturase. It is also believed that a deletion of the lanosterol 14alpha-demethylase gene, ERG11, is possible only under aerobic conditions when ERG3 is not functional. We tested these hypotheses by creating mutants by targeted deletion of the ERG3 and ERG11 genes and subjecting those mutants to antifungal susceptibility testing and sterol analysis. The homozygous erg3/erg3 mutant created, DSY1751, was resistant to azole derivatives, as expected. This mutant was, however, slightly more susceptible to amphotericin B than the parent wild type. It was possible to generate erg11/erg11 mutants in the DSY1751 background but also, surprisingly, in the background of a wild-type isolate with functional ERG3 alleles under aerobic conditions. This mutant (DSY1769) was obtained by exposure of an ERG11/erg11 heterozygous strain in a medium containing 10 micro g of amphotericin B per ml. Amphotericin B-resistant strains were obtained only from ERG11/erg11 heterozygotes at a frequency of approximately 5 x 10(-5) to 7 x 10(-5), which was consistent with mitotic recombination between the first disrupted erg11 allele and the other remaining functional ERG11 allele. DSY1769 was also resistant to azole derivatives. The main sterol fraction in DSY1769 contained lanosterol and eburicol. These studies showed that erg11/erg11 mutants of a C. albicans strain harboring a defective erg11 allele can be obtained in vitro in the presence of amphotericin B. Amphotericin B-resistant strains could therefore be selected by similar mechanisms during antifungal therapy.
Mots-clé
Aerobiosis Antifungal Agents/*pharmacology Blotting, Northern Blotting, Southern Candida albicans/drug effects/*genetics/*metabolism DNA Probes/metabolism Drug Resistance, Fungal/*genetics Ergosterol/*biosynthesis Microbial Sensitivity Tests Mutation/genetics/physiology Oxidoreductases/genetics/metabolism Phenotype Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:40
Dernière modification de la notice
09/05/2019 1:07
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