The Multifunctional Fungal Ergosterol

Abstract

The roles of ergosterol in the regulation of membrane fluidity and structure, as well its role as a target for the activity of antifungals, have been known for decades. Two recent studies, however, demonstrated that ergosterol is an immunologically active lipid that induces pyroptosis and that virtually all steps of its biosynthetic process are potential drug targets. In combination, those two reports strongly indicate that the biological relevance of ergosterol is broader than the current literature suggests.

Keywords: Candida albicans; Saccharomyces cerevisiae; antifungal agents; ergosterol; fungi; immunity.

FIG 1

The multiple roles of ergosterol in fungal cells. Ergosterol is a regulator of the fluidity of fungal membranes (left panel, classic view). On the basis of the structural differences between ergosterol and mammalian cholesterol, the antifungals allylamines, azoles, and morpholines can selectively inhibit 3 of the 25 enzymes required for biosynthesis of the fungal sterol. The studies by Koselny et al. (5) and Bhattacharya et al. (6) demonstrate novel roles for fungal ergosterol (right panel). Their observations imply that additional antifungal classes have the potential to target ergosterol biosynthesis and that this lipid interacts with the immune system, inducing pyroptosis. The immunological functions of ergosterol are compatible with the notion that this fungal sterol, rather than being limited to the plasma membrane, has a broad distribution in the fungal cell.