For a study, researchers sought to figure out how T. indotineae strains respond to itraconazole (ITC) and voriconazole (VRC). The study included 2 azole-sensitive strains (ITC MIC<0.125 g/mL; VRC MIC<0.06  μg/mL) and 4 azole-resistant strains (ITC MIC≥ 0.5  μg/mL; VRC MIC≥ 0.5 μg/mL). The expression of MDR genes encoding ABC family multidrug transporters with orthologs found in Trichophyton rubrum and CYP51A and CYP51B encoding azole antifungal chemical targets was compared between susceptible and resistant strains. In T. indotineae resistant strains, TinMDR3 and TinCYP51B  were overexpressed. TinMDR3 disruptants and parental strains overexpressing TinMDR3 showed minor variations in susceptibility. In 3 resistant bacteria, whole-genome sequencing indicated the formation of a varying number of TinCYP51B tandem repeats at a specific location in their genomes. The sensitivity of azole-resistant strains was restored after TinCYP51B was downregulated via RNA interference (RNAi). On the other hand, overexpression of TinCYP51B cDNA gave resistance to a susceptible T. indotineae strain. Finally, the lower azole sensitivity of T. indotineae strains was primarily due to TinCYP51B overexpression caused by more copies of this gene.

Source:journals.asm.org/doi/10.1128/aac.00059-22