Comparative Genomics of Two Sequential <i>Candida glabrata</i> Clinical Isolates.

Détails

Ressource 1Télécharger: 2413.full.pdf (2102.80 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_CDBF97BBE25A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Comparative Genomics of Two Sequential <i>Candida glabrata</i> Clinical Isolates.
Périodique
G3
Auteur(s)
Vale-Silva L., Beaudoing E., Tran VDT, Sanglard D.
ISSN
2160-1836 (Electronic)
ISSN-L
2160-1836
Statut éditorial
Publié
Date de publication
07/08/2017
Peer-reviewed
Oui
Volume
7
Numéro
8
Pages
2413-2426
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
<i>Candida glabrata</i> is an important fungal pathogen which develops rapid antifungal resistance in treated patients. It is known that azole treatments lead to antifungal resistance in this fungal species and that multidrug efflux transporters are involved in this process. Specific mutations in the transcriptional regulator <i>PDR1</i> result in upregulation of the transporters. In addition, we showed that the <i>PDR1</i> mutations can contribute to enhance virulence in animal models. In this study, we were interested to compare genomes of two specific <i>C. glabrata</i> -related isolates, one of which was azole susceptible (DSY562) while the other was azole resistant (DSY565). DSY565 contained a <i>PDR1</i> mutation (L280F) and was isolated after a time-lapse of 50 d of azole therapy. We expected that genome comparisons between both isolates could reveal additional mutations reflecting host adaptation or even additional resistance mechanisms. The PacBio technology used here yielded 14 major contigs (sizes 0.18-1.6 Mb) and mitochondrial genomes from both DSY562 and DSY565 isolates that were highly similar to each other. Comparisons of the clinical genomes with the published CBS138 genome indicated important genome rearrangements, but not between the clinical strains. Among the unique features, several retrotransposons were identified in the genomes of the investigated clinical isolates. DSY562 and DSY565 each contained a large set of adhesin-like genes (101 and 107, respectively), which exceed by far the number of reported adhesins (63) in the CBS138 genome. Comparison between DSY562 and DSY565 yielded 17 nonsynonymous SNPs (among which the was the expected <i>PDR1</i> mutation) as well as small size indels in coding regions (11) but mainly in adhesin-like genes. The genomes contained a DNA mismatch repair allele of <i>MSH2</i> known to be involved in the so-called hyper-mutator phenotype of this yeast species and the number of accumulated mutations between both clinical isolates is consistent with the presence of a <i>MSH2</i> defect. In conclusion, this study is the first to compare genomes of <i>C. glabrata</i> sequential clinical isolates using the PacBio technology as an approach. The genomes of these isolates taken in the same patient at two different time points exhibited limited variations, even if submitted to the host pressure.
Mots-clé
Candida glabrata/genetics, Candida glabrata/isolation & purification, Chromosomes, Fungal/genetics, Fungal Proteins/genetics, Genetic Variation, Genome, Fungal/genetics, Genomics, Humans, INDEL Mutation/genetics, Molecular Sequence Annotation, Nucleotides/genetics, Polymorphism, Single Nucleotide/genetics, Genome Report, adhesins, drug resistance, fungal pathogens, genome comparisons
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/07/2017 14:16
Dernière modification de la notice
20/08/2019 16:48
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