ABSTRACT
Candida albicans is the most frequent fungal species that causes infections in humans. Fluconazole is the main antifungal used to treat Candida infections, and its prolonged and indiscriminate use for the last decades are the most established causes which originated resistant strains. Fungal drug resistance is associated to alterations in ERG11 gene and overexpression of multidrug resistance (MDR) transporters belonging to two families: ATP-binding cassette (ABC) and Major Facilitator Superfamily (MFS). To evaluate the role of MFS transporters in azoles resistance of C. albicans clinical strains, this study aimed to analyze four Candida albicans clinical isolates from the University Hospital in Juiz de Fora (Minas Gerais/Brazil), selected in our previous study as they were unaffected by FK506, an ABC pumps inhibitor. In a primary investigation on MFS proteins overexpression, the extrusion of fluorescent substrates (rhodamine 6G and nile red) was analyzed by fluorescence microscopy and flow cytometry. Results suggest participation of MFS transporters in azole resistance of C. albicans isolates and indicate the existence of secondary resistance mechanisms. Therefore, this study contributes to the information about Candida albicans infections in Brazil and reinforces the importance of epidemiological studies focusing on an improved understanding of the disease and further resistance reversion.
Subject(s)
Antifungal Agents/pharmacology , Azoles/pharmacology , Candida albicans/drug effects , Membrane Transport Proteins/metabolism , Azoles/classification , Biological Transport/drug effects , Flow Cytometry , Humans , Membrane Transport Proteins/drug effects , Microbial Sensitivity Tests , Microscopy, Fluorescence , Tertiary Care CentersABSTRACT
La prevalencia de infecciones fúngicas invasivas ha aumentado en las últimas tres décadas debido al aumento de huéspedes inmunocomprometidos. Durante muchos años la anfotericina B y la flucitosina fueron los únicos antifúngicos disponibles para el tratamiento de estas micosis. Afortunadamente, en la última década el arsenal de antifúngicos se ha ampliado, lo que provee nuevas alternativas terapéuticas para los pacientes afectados. El objetivo de este artículo es resumir las características farmacológicas de los antifúngicos sistémicos tradicionales (anfotericina. flucitosina, itraconazol y fluconazol) y de los agentes antimicóticos de uso reciente: los nuevos triazoles (voriconazol, posaconazol) y las equinocandinas (caspofungina. micafungina y anidulofungina).
The prevalence of invasive fungal infections has increased over the past three decades owing to the increasing numbers of immunocompromised hosts. For many years, amphotericin Band flucytosine were the only available antifungal agents for invasive fungal infections. Fortunately, the antifungal drugs has increased, providing new therapeutic options for these patients. The purpose of this article is to summarize the pharmacologic profile of traditional antifungal drugs (amphotericin, flucytosine, itraconazole, fluconazole) as well as the ones recently licensed: the new triazoles (voriconazole, posaconazole) and the echinocandins (caspofungin, micafungin, anidulafungin).