The Sensitivity Modifying Activity of Nerolidol and α-Bisabolol Against Trichophyton spp.

Trichophyton spp. is one of the main causative agents of dermatophytosis such as tinea ungium and tinea pedis. Resistance to antifungal drugs is a significant clinical problem in dermatophytosis. The main molecular mechanism of antifungal resistance to conventional therapy in dermatophytes is the expression of efflux pumps. Efforts aimed at improving the efficacy of current antifungals such as griseofulvin are relevant. Given this, sesquiterpenes such as α-bisabolol and nerolidol found in essential oils represent promissing alternatives. Griseofulvin sensitivity modulation activity in T. rubrum, T. interdigitale H6, and T. interdigitale Δmdr2 (mutant strain of T. interdigitale) promoted by α-bisabolol and nerolidol were investigated. The minimum inhibitory concentration (MIC) of the test drugs were determined by microdilution. Subsequently, the effect of the drugs tested on plasma membrane functionality (K+ release) was analyzed. The MIC of griseofulvin was determined at sub-inhibitory sesquiterpene concentrations (modulation assay). An association study was performed with griseofulvin and sesquiterpenes (checkerboard). α-bisabolol was more potent than nerolidol; presenting lower MIC values. All of the fungi were sensitive to griseofulvin, starting at 8 µg/mL. With the exception of griseofulvin, all of the test drugs increased K+ release (p < 0.05). Nerolidol modulated the sensitivity of all strains to griseofulvin; α-bisabolol sensitivity modulation was limited to T. interdigitale H6 and T. interdigitale Δmdr2. In association with griseofulvin: nerolidol and α-bisabolol respectively presented synergism and additivity. Finally, the results of our study suggest using α-bisabolol and nerolidol compounds as potential antifungal agents and griseofulvin sensitivity modulators for Trichophyton spp.

Linalool modulates dermatophyte susceptibility to azole drugs.

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 concentration (MIC) of test-drugs were determined by microdilution. The modulating effect of linalool was evaluated by determining the MIC of the antifungals in the presence of subinhibitory concentrations of linalool. We also investigated the association effect (checkerboard) of linalool together with ketoconazole and itraconazole. The fungi became more sensitive to ketoconazole and itraconazole in the presence of linalool. The linalool and azole drug associations presented synergism.