Prenylated (iso)flavonoids as antifungal agents against the food spoiler Zygosaccharomyces parabailii

Species belonging to the Zygosaccharomyces bailii sensu lato clade are some of the most troublesome spoilage yeasts of acidic food products, primarily due to their resistance towards synthetic food preservatives, like weak organic acids. Therefore alternative, powerful and more natural antifungal agents are needed. Herein, prenylated isoflavonoids, present mainly in the Leguminosae family, were investigated for their antifungal properties (including potency and mode of action) against a Z. bailii food isolate, its interspecies hybrid, Z. parabailii. The mono-prenylated isoflavonoids, wighteone and glabridin were the most active, with minimum fungicidal concentrations (MFC) of 12.5 μg/mL (37 μM) and 25 μg/mL (77 μM), respectively, at pH 4.0, rendering them over 20 times (on weight basis) more potent than sorbic acid (MFC 550 μg/mL, 4.5 mM). The two active mono-prenylated isoflavonoids induced killing within 15 min, suggesting potential membrane activity. Membrane permeabilization by these molecules was confirmed by propidium iodide uptake and TEM imaging. Membrane permeabilization was accompanied with leakage of intracellular material. Molecular properties such as the electrostatic energy potential and the hydrophobic integy moment were correlated to activity through a binary classification quantitative structure-activity relationship (QSAR) model. Altogether, mono-prenylated isoflavonoids can serve as highly potent, novel and natural antifungal against Z. parabailii acting by severely compromising the membrane integrity.