Sporothrix spp. Biofilms Impact in the Zoonotic Transmission Route: Feline Claws Associated Biofilms, Itraconazole Tolerance, and Potential Repurposing for Miltefosine

孢子丝菌属生物膜对人畜共患病传播途径的影响:猫爪相关生物膜、伊曲康唑耐受性以及米替福新的潜在再利用

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作者:Giulia Maria Pires Dos Santos, Luana Pereira Borba-Santos, Taissa Vila, Isabella Dib Ferreira Gremião, Sandro Antonio Pereira, Wanderley De Souza, Sonia Rozental

Abstract

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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