ATP-binding Cassette (ABC) Transporter Proteins in Highly Terbinafine-resistant Strains of Trichophyton indotineae (Former Species Name: Trichophyton interdigitale)

Abstract

To clarify the terbinafine (TRF) resistance mechanism in highly TRF-resistant [minimum inhibitory concentration (MIC) >32 μg/mL] strains of Trichophyton indotineae (NUBS19006^T and NUBS19007), we investigated the expression of squalene epoxidase (SQLE), pleiotropic drug resistance 1 (PDR1), multidrug resistance 2 (MDR2), and MDR4 genes by real-time quantitative PCR analysis, given the known interaction of the corresponding proteins with antifungals and the efflux blocker tacrolimus (FK506). SQLE, PDR1, MDR2, and MDR4 transcript levels in TRF-resistant strains cultured in SDB were not significantly higher than those of the respective genes in TRF-susceptible strains (1 and 10). By contrast, PDR1, MDR2, and MDR4 transcript levels in TRF-resistant and TRF-susceptible strains cultured in SDB containing 10 μg/mL TRF were 5-100 times higher than those of the respective genes in strains grown in the absence of TRF. However, no differences in PDR1, MDR2, and MDR4 transcript levels were found between TRF-resistant (NUBS19006^T and NUBS19007) and TRF-susceptible strains cultured in SDB containing 10 μg/mL TRF. The interaction between TRF and FK506 on antifungal activity was not detected in TRF-resistant strains. These results indicate that ATP-dependent efflux pumps do not confer TRF-resistance mechanisms in TRF-resistant strains.