1887

Abstract

Sporotrichosis is a common mycosis caused by dimorphic fungi from the complex. In recent years, sporotrichosis incidence rates have increased in the Brazilian state of Rio de Janeiro, where is the species more frequently isolated from patients. The standard antifungals itraconazole and amphotericin B are recommended as first-line therapy for cutaneous/lymphocutaneous and disseminated sporotrichosis, respectively, although decreased sensitivity to these drugs was reported for clinical isolates of . Here, we evaluated the activity of the phospholipid analogue miltefosine – already in clinical use against leishmaniasis – towards the pathogenic yeast form of isolates with low sensitivity to itraconazole or amphotericin B . Miltefosine had fungicidal activity, with minimum inhibitory concentration (MIC) values of 1–2 µg ml. Miltefosine exposure led to loss of plasma membrane integrity, and transmission electron microscopy (TEM) analysis revealed a decrease in cytoplasmic electron density, alterations in the thickness of cell wall layers and accumulation of an electron-dense material in the cell wall. Flow cytometry analysis using an anti-melanin antibody revealed an increase in cell wall melanin in yeasts treated with miltefosine, when compared with control cells. The cytotoxicity of miltefosine was comparable to those of amphotericin B, but miltefosine showed a higher selectivity index towards the fungus. Our results suggest that miltefosine could be an effective alternative for the treatment of sporotrichosis, when standard treatment fails. Nevertheless, studies are required to confirm the antifungal potential of miltefosine for the treatment of sporotrichosis.

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2015-04-01
2020-01-21
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