Linalol modula a resistência de dermatófitos à fármacos azólicos.

Abstract

Dermatophytoses are infections that affect keratinized tissues such as the skin, nails and scalp. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of azole antifungal resistant strains has encouraged studies that aim to increase the arsenal of drugs that act on the defense mechanisms which confer multiple drug resistance. In this context, the terpenes drugs deserve attention. This study investigated the monoterpene linalool and its resistance modulating activity involving ergosterol biosynthesis inhibitors (ketoconazole, fluconazole and itraconazole) in strains of Microsporum spp. and Trichophyton spp. The minimum inhibitory concentrations (MIC) of linalool and the tested antifungals were initially determined using microdilution in RPMI 1640 medium. The modulating effect of linalool was evaluated by determining the MICs of the antifungals in the presence of sub-inhibitory concentrations of linalool. We also investigated the association effect (checkerboard) of linalool together with ketoconazole and itraconazole. One strain, Δmdr2 was used as the control, because it do not express genes that confer ABC transporter resistance. The fungi Trichophyton spp. and Microsporum spp. presented evidence of modulated resistance, becoming more sensitive to ketoconazole and itraconazole in the presence of linalool. The modulation did not occur with the Δmdr2 strain. The linalool and azole drug associations presented synergism. We conclude that linalool is a promising antifungal agent; inhibiting ABC transporter activity in dermatophytes.