Gene Amplification of : a New Mechanism of Resistance to Azole Compounds in Trichophyton indotineae.

Trichophyton indotineae causes dermatophytosis that is resistant to terbinafine and azole compounds. The aim of this study was to determine the mechanisms of resistance to itraconazole (ITC) and voriconazole (VRC) in strains of . Two azole-sensitive strains (ITC MIC < 0.125 μg/mL; VRC MIC < 0.06 μg/mL) and four azole-resistant strains (ITC MIC ≥ 0.5 μg/mL; VRC MIC ≥ 0.5 μg/mL) were used for the investigation. The expression of genes encoding multidrug transporters of the ABC family for which orthologs have been identified in Trichophyton rubrum and those of and encoding the targets of azole antifungal compounds were compared between susceptible and resistant strains. and were overexpressed in resistant strains. Only small differences in susceptibility were observed between disruptants and parental strains overexpressing Whole-genome sequencing of resistant strains revealed the creation of a variable number of tandem repeats at the specific position of their genomes in three resistant strains. Downregulation of by RNA interference (RNAi) restored the susceptibility of azole-resistant strains. In contrast, overexpression of cDNA conferred resistance to a susceptible strain of . In conclusion, the reduced sensitivity of strains to azoles is mainly due to the overexpression of resulting from additional copies of this gene.