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Synergic Effect of the Antimicrobial Peptide ToAP2 and Fluconazole on Candida albicans Biofilms.
do Nascimento Dias, Jhones; Hurtado Erazo, Fabián Andrés; Bessa, Lucinda J; Eaton, Peter; Leite, José Roberto de Souza de Almeida; Paes, Hugo Costa; Nicola, André Moraes; Silva-Pereira, Ildinete; Albuquerque, Patrícia.
Afiliação
  • do Nascimento Dias J; Laboratory of Molecular Biology of Fungi, University of Brasilia, Brasilia 70910-900, Brazil.
  • Hurtado Erazo FA; Laboratory of Molecular Biology of Fungi, University of Brasilia, Brasilia 70910-900, Brazil.
  • Bessa LJ; LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
  • Eaton P; LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
  • Leite JRSA; The Bridge, School of Chemistry, University of Lincoln, Lincoln LN6 7TS, UK.
  • Paes HC; Center for Research in Applied Morphology and Immunology, NuPMIA, University of Brasilia, Brasilia 70910-900, Brazil.
  • Nicola AM; Faculty of Medicine, University of Brasilia, Brasilia 70910-900, Brazil.
  • Silva-Pereira I; Faculty of Medicine, University of Brasilia, Brasilia 70910-900, Brazil.
  • Albuquerque P; Laboratory of Molecular Biology of Fungi, University of Brasilia, Brasilia 70910-900, Brazil.
Int J Mol Sci ; 25(14)2024 Jul 16.
Article em En | MEDLINE | ID: mdl-39063009
ABSTRACT
Candida albicans is one of the agents of invasive candidiasis, a life-threatening disease strongly associated with hospitalization, particularly among patients in intensive care units with central venous catheters. This study aimed to evaluate the synergistic activity of the antifungal peptide ToAP2 combined with fluconazole against C. albicans biofilms grown on various materials. We tested combinations of different concentrations of the peptide ToAP2 with fluconazole on C. albicans biofilms. These biofilms were generated on 96-well plates, intravenous catheters, and infusion tubes in RPMI medium at two maturation stages. Scanning electron microscopy and atomic force microscopy were employed to assess the biofilm structure. We also evaluated the expression of genes previously proven to be involved in C. albicans biofilm formation in planktonic and biofilm cells after treatment with the peptide ToAP2 using qPCR. ToAP2 demonstrated a synergistic effect with fluconazole at concentrations up to 25 µM during both the early and mature stages of biofilm formation in 96-well plates and on medical devices. Combinations of 50, 25, and 12.5 µM of ToAP2 with 52 µM of fluconazole significantly reduced the biofilm viability compared to individual treatments and untreated controls. These results were supported by substantial structural changes in the biofilms observed through both scanning and atomic force microscopy. The gene expression analysis of C. albicans cells treated with 25 µM of ToAP2 revealed a decrease in the expression of genes associated with membrane synthesis, along with an increase in the expression of genes involved in efflux pumps, adhesins, and filamentation. Our results highlight the efficacy of the combined ToAP2 and fluconazole treatment against C. albicans biofilms. This combination not only shows therapeutic potential but also suggests its utility in developing preventive biofilm tools for intravenous catheters.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Candida albicans / Fluconazol / Biofilmes / Sinergismo Farmacológico / Antifúngicos Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Candida albicans / Fluconazol / Biofilmes / Sinergismo Farmacológico / Antifúngicos Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça