Fluoride enhances the activity of fungicides that destabilize cell membranes

Fluoride has long been known to inhibit bacterial and fungal cell growth most likely by blocking the functions of key metabolic enzymes. In this study, we demonstrate that antifungal compounds that disrupt cell membrane integrity exhibit improved ability to inhibit cell growth when used with millimolar concentrations of fluoride. Specifically, antifungal compounds of the polyene class and an antifungal peptide exhibit synergy with fluoride to inhibit the growth of various fungal species, including Candida albicans. Our results demonstrate that certain compounds can be found that increase the cellular uptake of fluoride, and provide new opportunities for creating antimicrobial compounds whose functions are enhanced when combined with otherwise sub-inhibitory concentrations of small ions.