Synergism between the Antidepressant Sertraline and Caspofungin as an Approach to Minimise the Virulence and Resistance in the Dermatophyte Trichophyton rubrum

Autor(es)

Rocha, Carlos H. Lopes ; Rocha, Flaviane M. Galvao ; Bitencourt, Tamires A. ; Martins, Maira P. ; Sanches, Pablo R. ; Rossi, Antonio ; Martinez-Rossi, Nilce M.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF FUNGI; v. 8, n. 8, p. 13-pg., 2022-08-01.

Resumo

Trichophyton rubrum is responsible for several superficial human mycoses. Novel strategies aimed at controlling this pathogen are being investigated. The objective of this study was to evaluate the antifungal activity of the antidepressant sertraline (SRT), either alone or in combination with caspofungin (CASP). We calculated the minimum inhibitory concentrations of SRT and CASP against T. rubrum. Interactions between SRT and CASP were evaluated using a broth microdilution chequerboard. We assessed the differential expression of T. rubrum cultivated in the presence of SRT or combinations of SRT and CASP. We used MTT and violet crystal assays to compare the effect of SRT alone on T. rubrum biofilms with that of the synergistic combination of SRT and CASP. A human nail infection assay was performed. SRT alone, or in combination with CASP, exhibited antifungal activity against T. rubrum. SRT targets genes involved in the biosyntheses of cell wall and ergosterol. Furthermore, the metabolic activity of the T. rubrum biofilm and its biomass were affected by SRT and the combination of SRT and CASP. SRT alone, or in combination, shows potential as an approach to minimise resistance and reduce virulence. (AU)

• Processo FAPESP: 18/11319-1 - Fatores de transcrição e sinalização celular.
• Beneficiário: Maíra Pompeu Martins
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/23435-8 - Mecanismos moleculares envolvidos na resistência e na resposta adaptativa a inibidores fúngicos
• Beneficiário: Tamires Aparecida Bitencourt
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/22596-9 - Mecanismos moleculares associados à patogenicidade e resistência em fungos: estratégias para o tratamento de dermatofitoses
• Beneficiário: Nilce Maria Martinez-Rossi
• Modalidade de apoio: Auxílio à Pesquisa - Temático