Milteforan, a promising veterinary commercial product against feline sporotrichosis

Author(s)

Carnero, Laura C. Garcia ; Pinzan, Camila Figueiredo ; Diehl, Camila ; de Castro, Patricia Alves ; Pontes, Lais ; Rodrigues, Anderson Messias ; dos Reis, Thaila F. ; Goldman, Gustavo H.

• Document type: Journal article
• Source: MICROBIOLOGY SPECTRUM; v. 12, n. 10, p. 18-pg., 2024-08-28.

Abstract

Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. Due to its zoonotic transmission in Brazil, S. brasiliensis 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 of S. brasiliensis and S. schenckii have 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 activity in vitro against different strains of S. brasiliensis and S. schenckii. Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-alpha, 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 decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production. (AU)

• FAPESP's process: 22/08796-8 - Molecular characterization of putative effector proteins in the human fungal pathogen Aspergillus fumigatus
• Grantee: Camila Diehl da Rosa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 22/09882-5 - Investigation of the mechanisms of persistence and evolution of vorizonazole resistance in serial isolates obtained from the same human patient
• Grantee: Laís Pontes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/04977-5 - The identification of new pathways and compounds that can enhance caspofungin activity against Aspergillus fumigatus
• Grantee: Gustavo Henrique Goldman
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/08556-7 - Identification of new pathways and compounds that enhance Caspofungin and Voriconazole activity against Aspergillus fumigatus
• Grantee: Laura Cristina Garcia Carnero
• Support Opportunities: Scholarships in Brazil - Post-Doctoral