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Synergistic effects of phenolic compounds on Candida albicans DNA conformational changes during yeast-tohyphae transition
Candida albicans is a commensal microorganism in the mucosa of healthy individuals, but is also the most common cause of fungal infection among hospitalized U.S. patients, with elevated mortality rate. The increasing number of Candida species resistant to antifungal drugs has led to the application of novel strategies to treat this infection. Natural compounds such as phenolics have gained attention as potential agents against fungi. C. albicans has the ability to switch from yeast to hyphae cells, the most virulent form; therefore, therapies aiming to impair this morphologic transition can be promising against this fungus. The main objective of this work was to evaluate the ability of phenols to act synergistically to prevent yeast-to-hyphae transition of C. albicans by impacting DNA structural changes. Cells were treated with phenolic compounds in isolation or in combination and the inhibitory concentrations necessary to prevent hyphal growth by 50 % (IC50) were determined. Results from isobologram analyses showed that gallic (GA), ferulic (FA) and sinapic (SA) acids acting synergistically enhanced the inhibitory potential when compared to single compounds during a 24 h period. Untreated DNA samples were then extracted at four time points (0, 3,6,and 24 h) during morphologic switching using Fourier Transform Mid Infrared (FT-mIR) spectroscopy to understand DNA conformational changes, associated to nucleotide bases and phosphodiester-deoxyribose, in the progression of yeast-to-hyphal transformation. Later, cells were then treated with phenolics (GA, FA, GA+FA or GA+FA+SA) at IC50, incubated for 24 h and the DNA extracted to be analyzed by FT-mIR. Despite the same morphologic outcome (~50% of hyphae inhibition), different treatments led to different DNA phenotypes. For all treatments, FT-mIR bands were similar to the yeast or hyphal pattern, or different from both profiles. However, in samples treated with the phenolics cocktail, the spectra were similar to that of yeast DNA in the region expected to be most determinant to conformational changes. Overall, this work reports that GA, FA and SA acting synergistically presented an improved effect to suppress C. albicans morphologic transition by modulating DNA conformational changes that are known to regulate gene expression.
Camara, Cristiane Rodrigues S, "Synergistic effects of phenolic compounds on Candida albicans DNA conformational changes during yeast-tohyphae transition" (2015). ETD collection for University of Nebraska - Lincoln. AAI3738966.