The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata.

Détails

Ressource 1Demande d'une copieTélécharger: BIB_BB3261C7A883.P001.pdf (671.65 [Ko])
Etat: Supprimée
Version: Final published version
ID Serval
serval:BIB_BB3261C7A883
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata.
Périodique
Molecular Microbiology
Auteur(s)
Torelli R., Posteraro B., Ferrari S., La Sorda M., Fadda G., Sanglard D., Sanguinetti M.
ISSN
1365-2958[electronic]
Statut éditorial
Publié
Date de publication
2008
Volume
68
Numéro
1
Pages
186-201
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Our previous investigation on Candida glabrata azole-resistant isolates identified two isolates with unaltered expression of CgCDR1/CgCDR2, but with upregulation of another ATP-binding cassette transporter, CgSNQ2, which is a gene highly similar to ScSNQ2 from Saccharomyces cerevisiae. One of the two isolates (BPY55) was used here to elucidate this phenomenon. Disruption of CgSNQ2 in BPY55 decreased azole resistance, whereas reintroduction of the gene in a CgSNQ2 deletion mutant fully reversed this effect. Expression of CgSNQ2 in a S. cerevisiae strain lacking PDR5 mediated not only resistance to azoles but also to 4-nitroquinoline N-oxide, which is a ScSNQ2-specific substrate. A putative gain-of-function mutation, P822L, was identified in CgPDR1 from BPY55. Disruption of CgPDR1 in BPY55 conferred enhanced azole susceptibility and eliminated CgSNQ2 expression, whereas introduction of the mutated allele in a susceptible strain where CgPDR1 had been disrupted conferred azole resistance and CgSNQ2 upregulation, indicating that CgSNQ2 was controlled by CgPDR1. Finally, CgSNQ2 was shown to be involved in the in vivo response to fluconazole. Together, our data first demonstrate that CgSNQ2 contributes to the development of CgPDR1-dependent azole resistance in C. glabrata. The overlapping in function and regulation between CgSNQ2 and ScSNQ2 further highlight the relationship between S. cerevisiae and C. glabrata.
Mots-clé
4-Nitroquinoline-1-oxide/pharmacology, ATP-Binding Cassette Transporters/genetics, ATP-Binding Cassette Transporters/metabolism, Animals, Antifungal Agents/pharmacology, Azoles/pharmacology, Blotting, Southern, Candida glabrata/drug effects, Candida glabrata/genetics, Candidiasis/microbiology, Drug Resistance, Fungal/genetics, Female, Fungal Proteins/genetics, Fungal Proteins/metabolism, Mice, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/03/2009 19:06
Dernière modification de la notice
20/08/2019 16:29
Données d'usage