ArticleBrazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]2020
β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain.
Article in Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology], 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Batzelladine D, a Marine Natural Product, Reverses the Fluconazole Resistance Phenotype Mediated by Transmembrane Transporters inMarine drugs · 2024Article
- Antifungal activity of β-lapachone against a fluconazole-resistant Candida auris strain.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Synthesis of Altissimacoumarin D and Other Prenylated Coumarins and Their Ability to Reverse the Multidrug Resistance Phenotype inJournal of fungi (Basel, Switzerland) · 2023Article
- Digoxin Derivatives Sensitize aJournal of fungi (Basel, Switzerland) · 2022Article
- Repurposing the FDA-approved anticancer agent ponatinib as a fluconazole potentiator by suppression of multidrug efflux and Pma1 expression in a broad spectrum of yeast species.Microbial biotechnology · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe 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 cerevisiae mutant strain that overexpresses the ATP-binding cassette (ABC) transporter Pdr5p.
methodsThe evaluation of the antifungal activity of lapachones and their possible synergism with fluconazole against the mutant S. cerevisiae strain 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 PDR5 mRNA expression was assessed by RT-PCR. The release of hemoglobin was measured to evaluate the hemolytic activity of β-lapachone.
resultsα-nor-Lapachone and β-lapachone inhibited S. cerevisiae growth 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 PDR5 nor exerted hemolytic activity.
conclusionsData obtained indicate that β-lapachone is able to inhibit the S. cerevisiae efflux 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.
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