Academic Journal
Evolutionary accumulation of FKS1 mutations from clinical echinocandin-resistant Candida auris
| العنوان: | Evolutionary accumulation of FKS1 mutations from clinical echinocandin-resistant Candida auris |
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| المؤلفون: | Sufei Tian, Yusheng Wu, Hailong Li, Chen Rong, Na Wu, Yunzhuo Chu, Ning Jiang, Jingping Zhang, Hong Shang |
| المصدر: | Emerging Microbes and Infections, Vol 13, Iss 1 (2024) |
| بيانات النشر: | Taylor & Francis Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Infectious and parasitic diseases LCC:Microbiology |
| مصطلحات موضوعية: | Candida auris, echinocandin, resistance, FKS1 mutation, whole genome sequencing, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502 |
| الوصف: | Introduction: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods: Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). Interpretation: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 22221751 2222-1751 |
| Relation: | https://doaj.org/toc/2222-1751 |
| DOI: | 10.1080/22221751.2024.2377584 |
| URL الوصول: | https://doaj.org/article/9ef1e68a632245689a8bf3567ab0778a |
| رقم الانضمام: | edsdoj.9ef1e68a632245689a8bf3567ab0778a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22221751 |
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| DOI: | 10.1080/22221751.2024.2377584 |