Dermatófitos desenvolvem resistência aos monoterpenos geraniol e citronelol.

Abstract

Dermatophytoses are fungal infections in keratinized tissues such as nails, hairs and stratum corneum of the skin, produced by fungi called dermatophytes, the treatment of which has been a cause of great concern all over the world. This fact is justified by the appearance of strains resistant to the main antifungal agents used in clinical therapy, such as azole compounds. However, there are few studies that demonstrate the ability of dermatophytes to develop resistance after prolonged exposure to natural products, including terpenes. Geraniol and citronellol are monoterpenes with recognized antifungal potential. This study investigated the ability of dermatophyte strains (Trichophyton rubrum LM 305, Microsporum canis LM 216 and Microsporum gypseum LM 305) to acquire resistance to the monoterpenes citronellol and geraniol, and whether this resistance would occur cross-link between the monoterpenes themselves and with the drugs Azole ketoconazole, fluconazole and itraconazole. The stability of this resistance was then verified. Initially, the minimum inhibitory concentration (MIC) of the monoterpenes and azole drugs was determined by the microdilution method. Subsequently, the strains were submitted to 8 successive subcultures on Sabouraud dextrose agar containing subinhibitory concentrations of citronellol and geraniol. After this adaptation period, the microdilution of the drugs was performed to verify changes in the initial MIC values. Finally, the stability of the resistance was evaluated after 8 passages in tubes only with the drug-free culture medium, determining MIC also by microdilution. The results show that there was a change in the initial MICs of azole and natural products (ketoconazole 1,1,1 (μg / mL), fluconazole 2,2,2 (μg / mL), itraconazole 1,1,1 (μg / mL) ), Citronellol 64, 256, 256 (μg / mL) and geraniol 64, 128, 128 (μg / mL) for the strains of T. rubrum, M. canis and M. gypseum respectively. It was observed that dermatophytes are capable of acquiring resistance to monoterpenes, and this resistance occurs cross-linking with azole compounds and also between citronellol and geraniol. Finally, fungi reversed their profile of natural resistance when cultivated in the absence of drugs, since the azole resistance reversibility was not observed. Therefore, citronellol and geraniol may be considered as possible therapeutic alternatives, although controlled clinical studies are necessary to define the true efficacy, since they have been able to be effective against unlabeled strains, where the azole strains have remained resistant.