Histone acetylation increases in response to ferulic, gallic, and sinapic acids acting synergistically in vitro to inhibit Candida albicans yeast-to-hyphae transition

Novel treatments are needed to prevent candidiasis/candidemia infection due to the emergence of Candida species resistant to current antifungals. Considering the yeast-to-hyphae switch is a critical factor to Candida albicans virulence, phenols common in plant sources have been reported to demonstrating their ability to prevent dimorphism. Therefore, phenols present in many agricultural waste stress (ferulic (FA) and gallic (GA) acid) were initially screened in isolation for their yeast-to-hyphae inhibitory properties at times 3, 6, and 24 hr. Both FA and GA inhibited 50% of hyphae formation inhibitory concentration (IC ₅₀ ) but at a concentration of 8.0 ± 0.09 and 90.6 ± 1.05 mM, respectively, at 24 hr. However, the inhibitory effect of FA increased by 1.9–2.6 fold when combined with different GA concentrations. GA and FA values decreased even lower when sinapic acid (SA) was added as a third component. As evidenced by concave isobolograms and combination indexes less than 1, both GA:F A and GA:FA:SA combinations acted synergistically to inhibit 50% hyphae formation at 24 hr. Lastly, acetylation of histone H3 lysine 56 acetylation (H3K56) was higher in response to the triple phenolic cocktail (using the IC ₅₀ 24 hr inhibitory concentration level) comparable with the nontreated samples, indicating that the phenols inhibited hyphal growth in part by targeting H3K56 acetylation.