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Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study.
Fenley, Juliana de C; de Barros, Patrícia P; Carmo, Paulo H F do; Garcia, Maíra T; Rossoni, Rodnei D; Junqueira, Juliana C.
Afiliação
  • Fenley JC; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil.
  • de Barros PP; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil.
  • Carmo PHFD; Multicampi School of Medical Sciences, Federal University of Rio Grande do Norte (UFRN), Caicó, Rio Grande do Norte 59300-000, Brazil.
  • Garcia MT; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil.
  • Rossoni RD; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil.
  • Junqueira JC; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (Unesp), São José dos Campos, São Paulo 12245-000, Brazil.
Curr Issues Mol Biol ; 44(11): 5379-5389, 2022 Nov 01.
Article em En | MEDLINE | ID: mdl-36354676
Candida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new therapeutic strategies based on the perspective of drug repositioning, we evaluated the effects of two second-generation HIV-PIs, atazanavir (ATV) and darunavir (DRV), on virulence factors of C. albicans and experimental candidiasis. For this, clinical strains of C. albicans were subjected to in vitro and in vivo treatments with ATV or DRV. As a result, ATV and DRV exhibited antifungal activity against fungal cells at 512 µg/mL, reduced the viability and biomass of biofilms, and inhibited filamentation of C. albicans. In addition, these HIV-PIs downregulated the expression of SAP2 and BRC1 genes of C. albicans. In an in vivo study, prophylactic use of ATV and DRV prolonged the survival rate of Galleria mellonella larvae infected with C. albicans. Therefore, ATV and DRV showed activity against C. albicans by reducing cell growth, biofilm formation, filamentation, and expression of virulence genes. Furthermore, ATV and DRV decreased experimental candidiasis, suggesting the repurposing of HIV-PIs as antifungal treatments for C. albicans infections.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Revista: Curr Issues Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Revista: Curr Issues Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça