Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 9, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00699-21
Keywords
antifungal; naphthoquinone; Sporothrix spp.; zoonosis; cat; sporotrichosis; antifungal agents
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Funding
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2017/19374-9]
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Buparvaquone shows promising antifungal activity against Sporothrix brasiliensis, suggesting its potential as an alternative treatment for feline sporotrichosis.
Sporotrichosis has become an important zoonosis in Brazil, and Sporothrix brasiliensis is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex, was evaluated in vitro and in vivo against feline-borne isolates of S. brasiliensis. Buparvaquone inhibited in vitro fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for S. brasiliensis than mammalian cells. Yeasts treated with a subinhibitory concentration of buparvaquone exhibited mitochondrial dysfunction, reactive oxygen species and neutral lipid accumulation, and impaired plasma membranes. Scanning electron microscopy images also revealed buparvaquone altered cell wall integrity and induced cell disruption. in vivo experiments in a Galleria mellonella model revealed that buparvaquone (single dose of 5 mg/kg of body weight) is more effective than itraconazole against infections with S. brasiliensis yeasts. Combined, our results indicate that buparvaquone has a great in vitro and in vivo antifungal activity against S. brasiliensis, revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.
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