IADR Abstract Archives
A Natural Stilbene Tackles Candida Albicans Virulence
Objectives: With the scientific understanding of Candida pathogenesis, there is an acute need to develop antifungal strategies that are not broad-spectrum microbicides. The development of antifungal resistance is critically linked to strategies that inhibit fungal growth. Biofilm formation and filamentation are the recognised high value targets to tackle C. albicans virulence. The objective of this work is to investigate the effects of the natural stilbene piceatannol (PCT) in modulating C. albicansbiofilm formation and filamentation, without affecting its growth.
Methods: The effect of PCT was tested against C. albicans SC5314 planktonic growth, biofilm formation and filamentation using standard assays. Then, the effect of piceatannol on genes related to metabolism, virulence, hyphae and biofilm formation was analysed using qRT-PCR based transcriptomic studies. All the experiments were performed in triplicates as three individual experiments and analysed using non-parametric one-way ANOVA and Dunnet’s t-test. The statistical significance was set at P<0.05.
Results: None of the tested concentrations of PCT (200 to 0.05 μM) had any effect on the growth of planktonic cells. Sub-inhibitory concentrations (specifically 0.39 μM) significantly reduced biofilm formation compared to the untreated control (P<0.01). Notably the same biofilm-inhibitory concentrations also abolished yeast-to-hyphal transition (filamentation) under strong hyphae inducing conditions. qRT-PCR analysis revealed that PCT significantly downregulated (P<0.01) the master regulatory genes governing biofilm formation (BRP1, NDT80, ROB1) and hyphal morphogenesis (ALS3, HWP1, ECE1) in addition to ERG1, the key gene involved in ergosterol biosynthesis and PLB1, a gene that encodes phospholipase secretion in C. albicans in both yeast and hyphal cells.
Conclusions: This study provides the first evidence that piceatannol can inhibit C. albicans virulence phenotypes, highlighting a promising trend in the development of novel antifungal agents.
Methods: The effect of PCT was tested against C. albicans SC5314 planktonic growth, biofilm formation and filamentation using standard assays. Then, the effect of piceatannol on genes related to metabolism, virulence, hyphae and biofilm formation was analysed using qRT-PCR based transcriptomic studies. All the experiments were performed in triplicates as three individual experiments and analysed using non-parametric one-way ANOVA and Dunnet’s t-test. The statistical significance was set at P<0.05.
Results: None of the tested concentrations of PCT (200 to 0.05 μM) had any effect on the growth of planktonic cells. Sub-inhibitory concentrations (specifically 0.39 μM) significantly reduced biofilm formation compared to the untreated control (P<0.01). Notably the same biofilm-inhibitory concentrations also abolished yeast-to-hyphal transition (filamentation) under strong hyphae inducing conditions. qRT-PCR analysis revealed that PCT significantly downregulated (P<0.01) the master regulatory genes governing biofilm formation (BRP1, NDT80, ROB1) and hyphal morphogenesis (ALS3, HWP1, ECE1) in addition to ERG1, the key gene involved in ergosterol biosynthesis and PLB1, a gene that encodes phospholipase secretion in C. albicans in both yeast and hyphal cells.
Conclusions: This study provides the first evidence that piceatannol can inhibit C. albicans virulence phenotypes, highlighting a promising trend in the development of novel antifungal agents.