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

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

doi:10.3390/pathogens11020206

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.

Highlights

Sporotrichosis is a subacute or chronic infection caused by thermodimorphic fungi of the genus Sporothrix
In Brazil, sporotrichosis has an important zoonotic transmission route established between cats and humans and, in contrast with the classic route, the zoonotic infection is mainly caused by the species Sporothrix brasiliensis
We evaluated the ability of yeasts of S. brasiliensis and S. schenckii to form biofilms over sterilized cats’ claws in an ex vivo model of infected claws

Summary

Introduction

Sporotrichosis is a subacute or chronic infection caused by thermodimorphic fungi of the genus Sporothrix. It is a cosmopolitan disease affecting humans and other mammals, and the incidence is increasing worldwide, mainly in tropical and subtropical regions. Sporotrichosis is considered the most prevalent subcutaneous mycosis globally, and Brazil has the highest incidence [1]. Sporothrix schenckii is the species that is more prevalent worldwide and it is usually associated with soil-acquired infections. In Brazil, sporotrichosis has an important zoonotic transmission route established between cats and humans and, in contrast with the classic route, the zoonotic infection is mainly caused by the species Sporothrix brasiliensis. Cats actively participate in the transmission of the disease, with horizontal (cat–cat) and/or vertical (cat–human, cat–dog) transmission of Sporothrix species [2,3,4]

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Results

Conclusion