Milteforan, a promising veterinary commercial product against feline sporotrichosis.

Abstract

UNLABELLED: Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by theclinical clade species, includingand. Due to its zoonotic transmission in Brazil,represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains ofandhave shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activityagainst different strains ofand. Fluorescent miltefosine localizes to thecell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreasesfungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis. IMPORTANCE: Sporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreasesfungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production.