Currently, treatment options for fungal infections are limited due to the low availability of antifungal drugs and the rising of drug resistant strains. Thus, the development of new antifungal compounds and new therapeutic approaches are in great need for the control of these infections. The caffeic acid phenethyl ester (CAPE), caffeic acid (CA) and artepillin C (ARTC), compounds of propolis, have been considered to be promising due to its antifungal, immunomodulatory and anti-inflammatory action. Preferably, new agents should be effective against persisters cells, a subpopulation of fungal cells that show tolerance to conventional drugs. This is clinically important because persister cells are responsible for recurrent infections, such as oral candidiasis. Oral candidiasis is one of the most common human fungal infections and some in vitro studies have shown that, CAPE, CA and ARTC have antifungal activity inhibiting the growth of C. albicans. Thus, in vivo studies are necessary for evaluating the effectiveness of these alternative treatments. Therefore, the present study aims to determine if these compounds from propolis, alone or associated, will be able to inhibit the development of C. albicans persisters cells in G. mellonella model. Ten clinical strains of C. albicans isolated from oropharyngeal and invasive candidiasis will be studied. Firstly, mature biofilms of C. albicans strains will be surveyed for persisters after amphotericin B treatment (100 ¼g/ mL for 24 h) and CFU assay. These cells will be inoculated in G. mellonella and treated with variable concentrations of CAPE, CA and ARTC. The experimental infection will be assessed by survival curves, hemocyte density, cellular characterization of hemocytes by flow cytometry and by detection of real time C. albicans infection, using bioluminescence assay. The results will be analyzed selecting the most suitable statistical test for each analysis of this study, considering a significance level of 5% test.
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