| Autor: |
de Moraes, Daniel Clemente, Cardoso, Karina Martins, Domingos, Levy Tenório Sousa, do Carmo Freire Ribeiro Pinto, Maria, Monteiro, Robson Q., Ferreira-Pereira, Antônio |
| Zdroj: |
Brazilian Journal of Microbiology; 20240101, Issue: Preprints p1-10, 10p |
| Abstrakt: |
Objectives: The aim of this study was to evaluate the ability of lapachones in disrupting the fungal multidrug resistance (MDR) phenotype, using a model of study which an azole-resistant Saccharomyces cerevisiaemutant strain that overexpresses the ATP-binding cassette (ABC) transporter Pdr5p. Methods: The evaluation of the antifungal activity of lapachones and their possible synergism with fluconazole against the mutant S. cerevisiaestrain was performed through broth microdilution and spot assays. Reactive oxygen species (ROS) and efflux pump activity were assessed by fluorometry. ATPase activity was evaluated by the Fiske and Subbarow method. The effect of β-lapachone on PDR5mRNA expression was assessed by RT-PCR. The release of hemoglobin was measured to evaluate the hemolytic activity of β-lapachone. Results: α-nor-Lapachone and β-lapachone inhibited S. cerevisiaegrowth at 100 μg/ml. Only β-lapachone enhanced the antifungal activity of fluconazole, and this combined action was inhibited by ascorbic acid. β-Lapachone induced the production of ROS, inhibited Pdr5p-mediated efflux, and impaired Pdr5p ATPase activity. Also, β-lapachone neither affected the expression of PDR5nor exerted hemolytic activity. Conclusions: Data obtained indicate that β-lapachone is able to inhibit the S. cerevisiaeefflux pump Pdr5p. Since this transporter is homologous to fungal ABC transporters, further studies employing clinical isolates that overexpress these proteins will be conducted to evaluate the effect of β-lapachone on pathogenic fungi. |
| Databáze: |
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