Avaliação da atividade antifúngica de mirtenol sobre cepas de Aspergillus niger

Abstract

Aspergillus niger is a frequently isolated species characterized as an environmental contaminant and implicated in a variety of infections, such as Sick Building Syndrome. Furthermore, it is the third leading cause of aspergillosis. The limited arsenal of antifungals available, as well as the reported high fungal resistance, has driven the search for new substances with antifungal activity, with medicinal plants and their phytoconstituents being widely investigated for this purpose. In view of this, the aim of this study was to evaluate the antifungal activity of myrtenol on A. niger strains of environmental origin. For this, tests were performed to determine the Minimum Inhibitory Concentration (MIC); Minimum Fungicide Concentration (MFC); action on the mycelial growth of A. niger; elucidation of its mechanism of action and, finally, the effect of the association between myrtenol and the standard antifungals voriconazole and amphotericin B, through the Checkerboard method. Myrtenol showed strong antifungal activity against all strains of A. niger tested, with a MIC defined at 64 μg/mL and CFM of 256 μg/mL, showing fungicidal action. Amphotericin B exhibited a MIC of 4 μg/mL and CFM of 8 μg/mL. For voriconazole, MIC values of 2 μg/mL and CFM of 4 μg/mL were obtained. The antifungal effect of the sanitizer PAC 200® was observed only at its highest investigated concentration (10,000 μg/mL). Myrtenol significantly (p<0.05) inhibited, at CIMx2 (128 μg/mL) and CIMx4 (256 μg/mL), the mycelial growth of the standard strain (ATCC-6275) and the strain of environmental origin (LM-03) from A. niger, with results superior to those obtained for amphotericin B, which did not show a significant inhibitory effect. Voriconazole, in the three concentrations tested, showed a significant inhibition (p<0.001) on the mycelial growth of both strains. Myrtenol's antifungal mechanism of action possibly involves cell wall destabilization, as well as its binding to ergosterol in the fungal cytoplasmic membrane. A synergistic effect was observed in the combination of myrtenol with voriconazole, for both strains. However, the association between myrtenol and amphotericin B resulted in synergism for the ATCC-6245 strain and in additivity for the LM-03 strain. The findings of this research suggest that myrtenol represents a new and promising therapeutic alternative in the treatment of fungal infections caused by A. niger.