Phylogenomic analysis and genetic mechanisms of antifungal resistance in clinical isolates of <i>Candida glabrata</i> ( <i>Nakaseomyces glabratus</i> ) from across Canada, 2013–2020
Notice bibliographique
Résumé
ABSTRACT Candida glabrata ( Nakaseomyces glabratus ) is an important cause of invasive fungal infections and may exhibit reduced susceptibility toward antifungal drugs. Here, we used whole-genome sequencing to investigate the genomic phylogeny and identify genetic determinants of antifungal resistance in a collection of 142 clinical C. glabrata isolates obtained from the 10 provinces of Canada between 2013 and 2020. Our study prioritized resistant isolates ( n = 62, 43.7%) from invasive infections to better understand antifungal resistance and represents the largest national genomic survey of clinical C. glabrata isolates performed to date in Canada. Phylogenomic analysis based on single-nucleotide variants in the core genome revealed 15 genetically related clusters of C. glabrata . The largest cluster (cluster I, n = 29) was significantly associated with antifungal resistance ( P value = 0.0112). Antifungal-resistant isolates were present in almost all clusters, suggesting that resistance most likely arises from selective pressure during antifungal therapy, rather than dissemination of resistant clones. Thirty-six unique PDR1 variants were found in 38/52 (73.1%) fluconazole-resistant C. glabrata isolates, with more than half identified in this study as potential novel azole resistance variants. Well-characterized hot-spot variants in FKS genes ( n = 5) were found in 12/13 (92.3%) micafungin-resistant C. glabrata isolates. Our genomic analysis highlights the diversity in strain types and sheds light on potential genetic mechanisms of resistance in Canadian isolates of C. glabrata . IMPORTANCE Candida glabrata , also known as Nakaseomyces glabratus , is a type of yeast that can cause infections in individuals with weakened immune systems. Invasive infections can be difficult to treat since some C. glabrata isolates may not respond well to common antifungals. We studied a large collection of C. glabrata isolates collected from across Canada to better understand how C. glabrata spreads and why this fungal pathogen sometimes resists treatment. Using whole-genome sequence analysis, we found that drug resistance appears in different strains independently, likely as a result of treatment, rather than spreading from a single clone. We also identified specific mutations that may be linked to resistance to commonly used antifungal drugs, such as fluconazole and micafungin. Our research shows how valuable whole-genome sequencing is for understanding the spread and drug resistance of C. glabrata , which can help improve treatment and infection control.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».