Identification of genes involved in terbinafine resistance in Aspergillus nidulans

• Published in: Letters in applied microbiology Vol. 35; no. 3; pp. 228 - 232
• Main Authors: Rocha, E.M.F., Almeida, C.B., Martinez‐Rossi, N.M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2002
• Subjects: Antifungal Agents - pharmacology; Aspergillus nidulans - drug effects; Aspergillus nidulans - genetics; Chromosome Mapping; Drug Resistance, Fungal - genetics; Fungal Proteins - genetics; Microbial Sensitivity Tests; Mutation; Naphthalenes - pharmacology; Ultraviolet Rays
• ISSN: 0266-8254; 1472-765X
• DOI: 10.1046/j.1472-765X.2002.01174.x

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.