Interference of melanin in the susceptibility profile of Sporothrix species to amphotericin B

Abstract

Background: The presence of melanin in the fungal cell is a major virulence factor of the genus Sporothrix since it protects the fungal cells against the defense systems.

Aims: The present study aimed to investigate the interference of melanin in the susceptibility of Sporothrix brasiliensis and Sporothrix schenckii sensu stricto to amphotericin B and itraconazole, drugs recommended as therapy for disseminated and subcutaneous sporotrichosis, respectively.

Methods: Yeast cells were cultivated in minimal medium with or without l-DOPA in order to induce the production of melanin. Microdilution and killing assay methods were used to determine the antifungal activity against yeast cells with different amounts of melanin.

Results: The killing assay showed that melanization protected isolates within the S. schenckii complex from amphotericin B, particularly in the lower concentrations tested.

Conclusions: Studies combining amphotericin B and inhibitors of melanin are required in order to avoid this effect.

Keywords: Amphotericin B; Anfotericina B; Melanin; Melanina; Resistance; Resistencia; Sensibilidad; Sporothrix; Susceptibility.