<i>In Vitro</i> and <i>In Vivo</i> Antifungal Activity of Buparvaquone against <i>Sporothrix brasiliensis</i>

Abstract

Sporotrichosis has become an important zoonosis in Brazil, and <i>Sporothrix brasiliensis</i> 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 <i>in vitro</i> and <i>in vivo</i> against feline-borne isolates of <i>S. brasiliensis</i>. Buparvaquone inhibited <i>in vitro</i> fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for <i>S. brasiliensis</i> 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. <i>In vivo</i> 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 <i>S. brasiliensis</i> yeasts. Combined, our results indicate that buparvaquone has a great <i>in vitro</i> and <i>in vivo</i> antifungal activity against <i>S. brasiliensis</i>, revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.