In Vitro and In Vivo Antifungal Activity of Buparvaquone against Sporothrix brasiliensis

Autor(es):Mostrar menos -

Borba-Santos, Luana Pereira ^[1] ; Barreto, Thayna Lopes ^[2] ; Vila, Taissa ^[1] ; Chi, Kung Darh ^[3] ; Monti, Fabiana dos Santos ^[3] ; de Farias, Marconi Rodrigues ^[3] ; Alviano, Daniela S. ^[4] ; Alviano, Celuta S. ^[4] ; Futuro, Debora O. ^[5] ; Ferreira, Vitor ^[5] ; de Souza, Wanderley ^[6] ; Ishida, Kelly ^[2] ; Rozental, Sonia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Fungal Cell Biol, Rio De Janeiro - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Lab Antifungal Chemotherapy, Sao Paulo - Brazil

^[3] Pontificia Univ Catolica Parana, Sch Life Sci, Postgrad Program Anim Sci, Curitiba, Parana - Brazil

^[4] Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Gen Microbiol, Lab Microorganism Struct, Rio De Janeiro - Brazil

^[5] Fluminense Fed Univ, Fac Pharm, Pharmaceut Technol Dept, Niteroi, RJ - Brazil

^[6] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Cellular Ultrastruct Hertha Meyer, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Antimicrobial Agents and Chemotherapy; v. 65, n. 9 SEP 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/19374-9 - Equinocandinas no controle de infecções associadas a biofilmes polimicrobianos de Candida spp. e bactérias como Stapholococcus aureus e Pseudomonas aeruginosa
• Beneficiário: Kelly Ishida
• Modalidade de apoio: Auxílio à Pesquisa - Regular