Novel ERG11 and TAC1b mutations associated with azole resistance in Candida auris.
Détails
![Ressource 1](https://serval.unil.ch/static/img/forbidden.png)
Accès restreint UNIL
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_82EB6D2906CE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Novel ERG11 and TAC1b mutations associated with azole resistance in Candida auris.
Périodique
Antimicrobial agents and chemotherapy
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
01/05/2023
Peer-reviewed
Oui
Volume
65
Numéro
5
Pages
e02663-20
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Candida auris is a novel Candida species that has spread in all continents causing nosocomial outbreaks of invasive candidiasis. C. auris has the ability to develop resistance to all antifungal drug classes. Notably, many C. auris isolates are resistant to the azole drug fluconazole, a standard therapy of invasive candidiasis.Azole resistance in C. auris can result from mutations in the azole target gene ERG11 and/or overexpression of the efflux pump Cdr1. TAC1 is a transcription factor controlling CDR1 expression in C. albicans The role of TAC1 homologs in C. auris (TAC1a and TAC1b) remains to be better defined.In this study, we compared sequences of ERG11, TAC1a and TAC1b between a fluconazole-susceptible and five fluconazole-resistant C. auris isolates of clade IV. Among four of the resistant isolates, we identified a similar genotype with concomitant mutations in ERG11 (F444L) and TAC1b (S611P). The simultaneous deletion of tandemly arranged TAC1a/TAC1b resulted in a decrease of minimal inhibitory concentration (MIC) for fluconazole. Introduction of the ERG11 and TAC1b mutations separately and/or combined in the wild-type azole susceptible isolate resulted in a significant increase of azole resistance with a cumulative effect of the two combined mutations. Interestingly, CDR1 expression was not significantly affected by TAC1a/TAC1b deletion or by the presence of the TAC1b S611P mutation, suggesting the existence of Tac1-dependent and Cdr1-independent azole resistance mechanisms.We demonstrated the role of two previously unreported mutations responsible for azole resistance in C. auris, which were a common signature among four azole-resistant isolates of clade IV.
Pubmed
Web of science
Création de la notice
01/03/2021 12:40
Dernière modification de la notice
18/07/2024 7:06