Dermatophytes develop resistance to the monoterpenes geraniol and citronellol

Gustavo Nunes Cardoso, Kaltz Victor Souza Silva, Maria Islaine de Oliveira Lima, Juliana Moura Mendes Arrua, Fillipe de Oliveira Pereira

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Introduction: Dermatophytoses are fungal infections whose treatment has been the subject of much concern throughout the world. The emergence of antifungal resistance (azoles) in clinical therapeutics is well known. However, few studies demonstrate the capacity of dermatophytes to develop resistance against natural products such as terpenes. The monoterpenes geraniol and citronellol have recognized antifungal potential and are found in various essential oils.

Objectives: To investigate the capacity of Trichophyton rubrum, Microsporum canis, and Microsporum gypseum to acquire resistance against citronellol and geraniol.

Methods: The minimum inhibitory concentration of the tested drugs was determined by microdilution. The fungal strains were subjected to eight successive subcultures in Sabouraud dextrose agar containing the monoterpenes in sub-inhibitory concentrations. After this period of adaptation, the susceptibility profile to drugs was assessed by microdilution. Finally, after eight passages in culture medium without the drugs, resistance stability was again evaluated by microdilution test.

Results: From the initial citronellol and geraniol minimum inhibitory concentration values we observed an increase. In addition, a cross over effect was observed against the azole compounds. Finally, the fungi reversed their profiles of resistance against the natural drugs and showed no reversal in resistance to azoles. Although in dermatophytes the development of resistance to monoterpenes was observed, the phenomenon was not stable, as was observed against the azole drugs.

Conclusions: Citronellol and geraniol were active against resistant isolates even after dis-habituation. Thus these monoterpenes present themselves as potential therapeutic alternatives with fewer complications in the emergence of resistance.

Palabras clave

resistance; antifungal; habituation; terpenes; azoles

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