Daniel Clemente Moraes , Leandro Figueira Reis de Sá , Levy Tenorio Sousa Domingos , Maria do Carmo Freire Ribeiro Pinto , Rosangela Maria de Araújo Soares , Antônio Ferreira-Pereira
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引用次数: 3
Abstract
Background
Mortality rate of invasive Candida infections is raising mainly amongst immunocompromised patients. These infections are hard-to-treat mainly due to the increasing incidence of resistance. The overexpression of ATP-binding cassette and major facilitator superfamily transporters is the main responsible for the failure of antifungal therapies. In a Saccharomyces cerevisiae model, β-lapachone inhibited Pdr5p, a transporter homologous to those found in Candida albicans.
Aims
To determine whether β-lapachone reverses the resistance phenotype mediated by efflux transporters in C. albicans clinical isolates.
Methods
The antifungal activity of β-lapachone combined with fluconazole was measured by agarose chemosensitization and microdilution assays. CaCdr2p and CaMdr1p activities were evaluated through fluorescent dyes accumulation. ATPase activity was assessed using transporter-enriched plasma membranes.
Results
β-lapachone reverted antifungal resistance of S. cerevisiae and C. albicans strains overexpressing CaCdr2p and CaMdr1p transporters by inhibiting these proteins activities. CaCdr2p ATPase activity was not impaired by the compound.
Conclusions
β-lapachone is a promising drug candidate to be used as an adjuvant in the treatment of candidiasis caused by fluconazole-resistant C. albicans strains.
期刊介绍:
Revista Iberoamericana de Micología (Ibero-American Journal of Mycology) is the official journal of the Asociación Española de Micología, Asociación Venezolana de Micología and Asociación Argentina de Micología (The Spanish, Venezuelan, and Argentinian Mycology Associations). The Journal gives priority to publishing articles on studies associated with fungi and their pathogenic action on humans and animals, as well as any scientific studies on any aspect of mycology. The Journal also publishes, in Spanish and in English, original articles, reviews, mycology forums, editorials, special articles, notes, and letters to the editor, that have previously gone through a scientific peer review process.