Identification of genes involved in terbinafine resistance in Aspergillus nidulans.
OBJECTIVE
To determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in humans.


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.


CONCLUSIONS
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.
Departamento de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
E M F
EM
Rocha
C B
CB
Almeida
N M
NM
Martinez-Rossi
D000935:Antifungal Agents / Q000494:pharmacology*; D001233:Aspergillus nidulans / Q000187:drug effects* / Q000235:genetics; D002874:Chromosome Mapping; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009281:Naphthalenes / Q000494:pharmacology*; D000077291:Terbinafine; D014466:Ultraviolet Rays
D000935:Antifungal Agents; D005656:Fungal Proteins; D009281:Naphthalenes; D000077291:Terbinafine