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

• Document type: Journal article
• Source: FUTURE MICROBIOLOGY; v. N/A, p. 10-pg., 2025-02-05.

Abstract

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)

• FAPESP's process: 20/15586-4 - Establishment of a three-dimensional model to determine the pharmacological efficacy and safety of nitrofuran and indoles derivatives and evaluation of Histoplasma capsulatum infection
• Grantee: Carolina Orlando Vaso
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/22188-8 - Evaluation of the interaction of biofilms mono and dual-species of Candida spp and dermatophytes photodynamic therapy combined with 2-chalcone
• Grantee: Níura Madalena Bila
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 21/03805-6 - Monospecies and mixed biofilms of Trichophyton and Staphylococcus: influence of nutrients and presence of persister cells
• Grantee: Jenyffie Araujo Belizario
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 22/15826-0 - From the development of three-dimensional human lung models of infection to the evolution of functional human lung models for studying the interaction with Histoplasma capsulatum biofilm
• Grantee: Ana Marisa Fusco Almeida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/18388-6 - Role of biofilm in the pathogenesis of dermatophytosis and development of combat strategies
• Grantee: Caroline Barcelos Costa Orlandi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral