Journal
PATHOGENS
Volume 11, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/pathogens11020206
Keywords
biofilms; cat claws; miltefosine; Sporothrix brasiliensis; Sporothrix schenckii
Categories
Funding
- CoordenacAo de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [88882.316588/2019-01]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- FundacAo Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ) [E-15/2019PDRE, E26/200.704/2021]
- Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) [312238/2020-7]
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Sporotrichosis is a common subcutaneous fungal infection caused by direct inoculation of Sporothrix spp. from soil to the skin. Cats play an important role in the zoonotic transmission of sporotrichosis in hot-spot endemic areas like Brazil. Biofilms formed by Sporothrix yeasts contribute to the recurrence of infection and resistance to antifungal drugs like itraconazole. Miltefosine shows potential as an off-label alternative to itraconazole by demonstrating antibiofilm activity against Sporothrix biofilms.
Sporotrichosis is the most prevalent subcutaneous mycosis globally, and it is typically caused by direct inoculation of the soil saprophytic fungus Sporothrix spp. into the patients' skin. However, sporotrichosis has an important zoonotic transmission route between cats and humans in hot-spot endemic areas such as Brazil. Antifungal itraconazole is the first-line treatment; however, it is frequently associated with recurrence after withdrawal, mainly on cats. Biofilms are important resistance structures related to the environmental persistence of most microorganisms. In the present work, we evaluated Sporothrix yeasts' ability to form biofilms in an ex vivo model of infected claws of cats. Using scanning electron microscopy, we demonstrated the presence of fungal biofilms in the claws of cats diagnosed with sporotrichosis confirmed by isolation of Sporothrix spp. in culture. We present here evidence of antibiofilm activity of miltefosine and suggest its use off-label as an antifungal as a putative alternative to itraconazole against Sporothrix biofilms. Claw contamination could sustain infections through a continuous inoculation cycle between open lesions and cat claws. Our results further support the off-label use of miltefosine as a promising alternative, especially for mycosis refractory to conventional treatment.
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