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Updated: May 3, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Induction of Antifungal Tolerance Reveals Genetic and Phenotypic Changes in Candida glabrata
Christy Chedraoui1, Nour Fattouh1,2, Setrida El Hachem1
1Department of Biological Sciences, Lebanese American University, Byblos P.O. Box 36, Lebanon.
Abstract:
Candida glabrata is an opportunistic, pathogenic fungus that is increasingly isolated from hospitalized patients. The incidence of drug tolerance, heteroresistance, and resistance is on the rise due to an overuse of antifungal drugs. The aim of this study was to expose a sensitive C. glabrata strain to sequentially increasing concentrations of two antifungal drugs, fluconazole, an azole that targets ergosterol biosynthesis, or caspofungin, an echinocandin that targets cell wall glucan synthesis. Analysis of the drug-exposed isolates showed development of antifungal tolerance, chromosomal abnormalities, decreased adhesion, attenuated virulence, and an increase in efflux pump activity. Furthermore, whole genome sequencing of all isolates exposed to different concentrations of fluconazole or caspofungin was performed to determine mutations in key genes that could correlate with the observed phenotypes. Mutations were found in genes implicated in adhesion, such as in the AWP, PWP, and EPA family of genes. Isolates exposed to higher drug concentrations displayed more mutations than those at lower concentrations.
Insights
Antifungal drug exposure in Candida glabrata led to drug tolerance, chromosomal changes, and reduced virulence. Whole genome sequencing revealed mutations in adhesion genes, increasing with drug concentration.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
Background:
- * *Candida glabrata* is an opportunistic fungal pathogen frequently isolated from hospitalized individuals.
- * Rising antifungal drug resistance necessitates understanding resistance mechanisms.
Purpose of the Study:
- * To investigate the effects of sequential exposure to fluconazole or caspofungin on a sensitive *C. glabrata* strain.
- * To identify genetic mutations associated with observed phenotypic changes.
Main Methods:
- * Sequential exposure of *C. glabrata* to increasing concentrations of fluconazole or caspofungin.
- * Phenotypic analysis including drug tolerance, adhesion, and virulence assays.
- * Whole genome sequencing to identify mutations.
Main Results:
- * Drug-exposed isolates developed antifungal tolerance, chromosomal abnormalities, decreased adhesion, and increased efflux pump activity.
- * Mutations were identified in adhesion-related genes (*AWP*, *PWP*, *EPA* families).
- * Higher drug concentrations correlated with a greater number of mutations.
Conclusions:
- * Sequential exposure to antifungals induces tolerance and genetic alterations in *C. glabrata*.
- * Mutations in adhesion genes are linked to drug exposure.
- * Understanding these mechanisms is crucial for managing *C. glabrata* infections.
