Identification of genes involved in terbinafine resistance in Aspergillus nidulans
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 m...
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Published in | Letters in applied microbiology Vol. 35; no. 3; pp. 228 - 232 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
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Oxford, UK
Blackwell Science Ltd
01.01.2002
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Abstract | 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. |
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AbstractList | AIMSTo 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 RESULTSFour 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.CONCLUSIONSPeriodic 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 STUDYThe 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. 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. To determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in humans. 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. 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. 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. |
Author | Almeida, C.B. Rocha, E.M.F. Martinez‐Rossi, N.M. |
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References_xml | – volume: 81 start-page: 1432 year: 1991 end-page: 1438 article-title: Inheritance of resistance to fenpropimorph and terbinafine, two sterol biosynthesis inhibitors in publication-title: Phytopathology – volume: 126 start-page: 2 issue: Suppl. 39 year: 1992 end-page: 7 article-title: Terbinafine: mode of action and properties of the squalene epoxidase inhibition publication-title: British Journal of Dermatology – volume: 37 start-page: 979 year: 1997 end-page: 988 article-title: Terbinafine: An update publication-title: Journal of American Academy of Dermatology – volume: 1517 start-page: 177 year: 2001 end-page: 189 article-title: Positive and negative regulation of squalene synthase ( ), an ergosterol biosynthetic gene in publication-title: Biochimica et Biophysica Acta – volume: 79 start-page: 169 year: 1980 end-page: 172 article-title: Membrane‐damaging agents cause mitotic non‐disjunction in publication-title: Mutation Research – volume: 268 start-page: 914 year: 2001 end-page: 924 article-title: A novel sequence element is involved in the transcriptional regulation of expression of the ERG1 (squalene epoxidase) gene in publication-title: European Journal of Biochemistry – volume: 8 start-page: 14 year: 1952 end-page: 15 article-title: Production of heterozygous diploids in filamentous fungi publication-title: Experientia – volume: 143 start-page: 405 year: 1997 end-page: 416 article-title: Cloning of genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene publication-title: Microbiology-UK – volume: 171 start-page: 103 year: 1999 end-page: 106 article-title: Identification and linkage mapping of the gene of , where mutation affects growth and pigmentation of colonies in a temperature‐ and pH‐dependent way publication-title: FEMS Microbiology Letters – volume: 12 start-page: 477 year: 1989 end-page: 484 article-title: Characterization of benomyl resistant mutants of publication-title: Rev. Bras. Genet. – volume: 31 start-page: 1365 year: 1987 end-page: 1368 article-title: Antifungal activity of the allylamine derivative in vitro publication-title: Antimicrobial Agents and Chemotherapy – volume: 64 start-page: 167 year: 1999 end-page: 184 article-title: Mechanisms of resistance to fenpropimorph and terbinafine, two sterol biosynthesis inhibitors. , a phytopathogenic fungus publication-title: Pesticide Biochemistry and Physiology – volume: 5 start-page: 141 year: 1953 end-page: 238 article-title: The genetics of publication-title: Advances in Genetics – volume: 120 start-page: 183 year: 1994 end-page: 186 article-title: The effect of gene on the vegetative growth of benomyl‐resistant strains of publication-title: FEMS Microbiology Letters |
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Snippet | 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.... To determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in humans. Four... AIMSTo determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in... |
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SubjectTerms | 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 |
Title | Identification of genes involved in terbinafine resistance in Aspergillus nidulans |
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