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Updated: Sep 29, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Identification of genes involved in terbinafine resistance in Aspergillus nidulans
E M F Rocha1, C B Almeida, N M Martinez-Rossi
1Departamento de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
Aims:
To determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in humans.
Methods And Results:
Four resistant mutants from Aspergillus nidulans isolated after irradiation with ultraviolet light were crossed with the master strain F (MSF). Genetic analysis revealed that a single gene, located on chromosome IV, is responsible for resistance to terbinafine and that the alleles responsible for this resistance in these mutants are of a codominant or dominant nature at high terbinafine concentrations. Furthermore, the interaction of this mutation with another one identified on chromosome II causes the double mutant to be highly resistant.
Conclusions:
Periodic surveillance of antimycotic susceptibility would be an important measure in detecting the emergence and spread of resistance. Mutation in a single gene could be responsible for resistance to terbinafine and a genic interaction may be responsible for a higher level of antimycotic resistance.
Significance And Impact Of The Study:
The understanding of the mechanisms that lead to changes in the sensitivity of a fungus to a given antifungal agent is important both in order to define strategies for the use of such agent and to guide the development of new antifungal agents.
Insights
A single gene mutation causes terbinafine resistance in fungi. Gene interactions can lead to higher resistance, highlighting the need for antifungal susceptibility surveillance.
Area of Science:
- Mycology
- Medical Mycology
- Antimicrobial Resistance
Background:
- Terbinafine is a key antifungal drug for human fungal infections.
- Understanding fungal resistance mechanisms is crucial for effective treatment and drug development.
Purpose of the Study:
- To investigate the genetic basis of terbinafine resistance in Aspergillus nidulans.
- To identify the specific genes and genetic interactions conferring resistance.
Main Methods:
- Induction of mutations in Aspergillus nidulans using ultraviolet light.
- Genetic crosses between resistant mutants and a master strain.
- Analysis of gene location and inheritance patterns.
Main Results:
- A single gene on chromosome IV controls terbinafine resistance.
- Resistance alleles exhibit codominant or dominant traits at high drug concentrations.
- A second mutation on chromosome II, interacting with the primary resistance gene, results in high-level resistance.
Conclusions:
- Fungal resistance to terbinafine is primarily governed by a single gene.
- Gene interactions can significantly amplify antifungal resistance.
- Regular monitoring of antifungal susceptibility is essential to track resistance emergence.
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