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Antimicrobial Agents and Chemotherapy, September 2004, p. 3530-3535, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3530-3535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Terbinafine Resistance Mediated by Salicylate 1-Monooxygenase in Aspergillus nidulans

Marcia A. S. Graminha,1 Eleusa M. F. Rocha,1 Rolf A. Prade,2 and Nilce M. Martinez-Rossi1*

Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil,1 Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, Oklahoma2

Received 6 February 2004/ Returned for modification 21 March 2004/ Accepted 19 May 2004

Resistance to antifungal agents is a recurring and growing problem among patients with systemic fungal infections. UV-induced Aspergillus nidulans mutants resistant to terbinafine have been identified, and we report here the characterization of one such gene. A sib-selected, 6.6-kb genomic DNA fragment encodes a salicylate 1-monooxygenase (salA), and a fatty acid synthase subunit (fasC) confers terbinafine resistance upon transformation of a sensitive strain. Subfragments carrying salA but not fasC confer terbinafine resistance. salA is present as a single-copy gene on chromosome VI and encodes a protein of 473 amino acids that is homologous to salicylate 1-monooxygenase, a well-characterized naphthalene-degrading enzyme in bacteria. salA transcript accumulation analysis showed terbinafine-dependent induction in the wild type and the UV-induced mutant Terb7, as well as overexpression in a strain containing the salA subgenomic DNA fragment, probably due to the multicopy effect caused by the transformation event. Additional naphthalene degradation enzyme-coding genes are present in fungal genomes, suggesting that resistance could follow degradation of the naphthalene ring contained in terbinafine.

* Corresponding author. Mailing address: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, Sao Paulo, Brazil. Phone: 55-16-602-3150. Fax: 55-16-633-0069. E-mail: nmmrossi{at}usp.br.

Antimicrobial Agents and Chemotherapy, September 2004, p. 3530-3535, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3530-3535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fachin, A. L., Ferreira-Nozawa, M. S., Maccheroni, W. Jr, Martinez-Rossi, N. M. (2006). Role of the ABC transporter TruMDR2 in terbinafine, 4-nitroquinoline N-oxide and ethidium bromide susceptibility in Trichophyton rubrum.. J Med Microbiol 55: 1093-1099 [Abstract] [Full Text]  
  • Rocha, E. M. F., Gardiner, R. E., Park, S., Martinez-Rossi, N. M., Perlin, D. S. (2006). A Phe389Leu Substitution in ErgA Confers Terbinafine Resistance in Aspergillus fumigatus.. Antimicrob. Agents Chemother. 50: 2533-2536 [Abstract] [Full Text]  


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