Efficacy of nitrofuran derivatives against biofilms of Histoplasma capsulatum strains and their in vivo toxicity

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Vaso, Carolina Orlando ; Bila, Niura Madalena ; da Silva, Rosangela Aparecida Moraes ; de Carvalho, Angelica Romao ; Belizario, Jennyfie Araujo ; Pandolfi, Fabiana ; De Vita, Daniela ; Bortolami, Martina ; Mendes-Giannini, Maria Jose Soares ; Scipione, Luigi ; Di Santo, Roberto ; Costi, Roberta ; Costa-Orlandi, Caroline Barcelos ; Fusco-Almeida, Ana Marisa

• Tipo de documento: Artigo Científico
• Fonte: FUTURE MICROBIOLOGY; v. N/A, p. 10-pg., 2025-02-05.

Resumo

AimTo evaluate the efficacy of two nitrofuran derivatives against biofilms formed by two strains of Histoplasma capsulatum and to study the toxicity of these compounds in alternative models: Caenorhabditis elegans, Galleria mellonella, and zebrafish.MethodsThe metabolic activity of biofilms was measured after treatment using the XTT reduction assay. Scanning electron microscopy (SEM) and confocal microscopy were used to observe damage to mature biofilms. Survival curves were generated for G. mellonella, while percentage survival was determined for C. elegans and zebrafish.ResultsThe compounds showed efficacy against early and mature biofilms at concentrations equal to or up to two times higher than those required to eliminate planktonic fungal cells (3.90 to 31.25 mu g/mL). Micrographs showed a reduction in metabolic activity, biofilm thickness, and extracellular matrix. In addition, the compounds showed little or no toxicity in alternative models, even at the highest concentrations tested.ConclusionThese results are promising for the development of new therapeutic alternatives, especially for species, such as H. capsulatum, which are recognized as high-priority pathogens. Few studies have investigated resistance and antifungal treatment targeting biofilms of this species, making this work a relevant contribution to future approaches. (AU)

• Processo FAPESP: 20/15586-4 - Estabelecimento de um modelo tridimensional para determinação da eficácia e segurança farmacológica de derivados de nitrofuranos e indólicos e avaliação da infecção de Histoplasma capsulatum
• Beneficiário: Carolina Orlando Vaso
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 19/22188-8 - Avaliação da interação de biofilmes mono e dual-espécies de Candida spp e dermatófitos combinada a terapia fotodinâmica com 2-chalcona
• Beneficiário: Níura Madalena Bila
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 21/03805-6 - Biofilmes mono-espécie e mistos de Trichophyton e Staphylococcus: influência de nutrientes e presença de células persisters
• Beneficiário: Jenyffie Araujo Belizario
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 22/15826-0 - Do desenvolvimento de modelos pulmonares humanos tridimensionais de infecção à evolução de modelos pulmonares humanos funcionais para o estudo da interação com biofilme de Histoplasma capsulatum
• Beneficiário: Ana Marisa Fusco Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/18388-6 - O papel do biofilme na patogênese das dermatofitoses e desenvolvimento de estratégias de combate
• Beneficiário: Caroline Barcelos Costa Orlandi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado