Terbinafine resistance conferred by multiple copies of the salicylate 1-monooxygenase gene in Trichophyton rubrum

Med Mycol. 2018 Apr 1;56(3):378-381. doi: 10.1093/mmy/myx044.

Abstract

Resistance to antifungals is a leading concern in the treatment of human mycoses. We demonstrate that the salA gene, encoding salicylate 1-monooxygenase, is involved in resistance of the dermatophyte Trichophyton rubrum to terbinafine, one of the most effective antifungal drugs against dermatophytes. A strain with multiple copies of salA was constructed and exhibited elevated expression of salA and increased terbinafine resistance. This reflects a mechanism not yet reported in a pathogenic fungus.

MeSH terms

  • Antifungal Agents / pharmacology
  • Drug Resistance, Fungal / drug effects
  • Drug Resistance, Fungal / genetics*
  • Genes, Fungal / genetics
  • Microbial Sensitivity Tests
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism*
  • Terbinafine / pharmacology*
  • Transcription, Genetic
  • Transformation, Genetic
  • Trichophyton / drug effects*
  • Trichophyton / enzymology
  • Trichophyton / genetics*
  • Up-Regulation / genetics

Substances

  • Antifungal Agents
  • Mixed Function Oxygenases
  • salicylate 1-monooxygenase
  • Terbinafine