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Updated: Jun 23, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
A Whole Genome Sequencing-Based Approach to Track down Genomic Variants in Itraconazole-Resistant Species of
Sanaz Nargesi1,2, Reza Valadan3, Mahdi Abastabar1,2
1Department of Medical Mycology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 4815733971, Iran.
Abstract:
The antifungal resistance in non-fumigatus Aspergillus spp., as well as Aspergillus fumigatus, poses a major therapeutic challenge which affects the entire healthcare community. Mutation occurrence of cyp51 gene paralogs is the major cause of azole resistance in Aspergillus spp. To obtain a full map of genomic changes, an accurate scan of the entire length of the Aspergillus genome is necessary. In this study, using whole genome sequencing (WGS) technique, we evaluated the mutation in cyp51A, cyp51B, Cdr1B, AtrR, Hmg1, HapE and FfmA genes in different clinical isolates of Aspergillus fumigatus, Aspergillus niger, Aspergillus tubingensis, Aspergillus welwitschiae and Aspergillus terreus which responded to minimum inhibitory concentrations of itraconazole above 16 µg mL-1. We found different nonsynonymous mutations in the cyp51A, cyp51B, Cdr1B, AtrR, Hmg1, HapE and FfmA gene loci. According to our findings, Aspergillus species isolated from different parts of the world may represent different pattern of resistance mechanisms which may be revealed by WGS.
Insights
Antifungal resistance in Aspergillus species is a growing concern. Whole genome sequencing revealed mutations in key genes, offering insights into azole resistance mechanisms across different Aspergillus species globally.
Area of Science:
- Medical Mycology
- Genomics
- Antimicrobial Resistance
Background:
- Antifungal resistance in Aspergillus species, including non-fumigatus and Aspergillus fumigatus, presents a significant challenge in healthcare.
- Mutations in the cyp51 gene are a primary driver of azole resistance in Aspergillus species.
Purpose of the Study:
- To investigate genomic alterations associated with azole resistance in clinical isolates of various Aspergillus species.
- To identify specific gene mutations contributing to high-level itraconazole resistance.
Main Methods:
- Whole genome sequencing (WGS) was employed to analyze mutations in targeted genes.
- Clinical isolates of Aspergillus fumigatus, Aspergillus niger, Aspergillus tubingensis, Aspergillus welwitschiae, and Aspergillus terreus with high itraconazole minimum inhibitory concentrations (MICs > 16 µg mL-1) were studied.
Main Results:
- Nonsynonymous mutations were identified in the cyp51A, cyp51B, Cdr1B, AtrR, Hmg1, HapE, and FfmA genes across the studied Aspergillus species.
- Distinct mutation patterns were observed, suggesting geographically varied resistance mechanisms.
Conclusions:
- Whole genome sequencing is crucial for a comprehensive understanding of genomic changes driving antifungal resistance.
- Geographic origin may influence the specific resistance mechanisms employed by different Aspergillus species.
