Exploring the link between iron availability and fluconazole activity against Candida glabrata

Abstract

"Invasive fungal infections (IFIs) represent a significant health concern worldwide, as recently acknowledged by the World Health Organization with the release of the first priority list of fungal pathogens. Fluconazole remains the most frequently prescribed antifungal for treating IFIs due to its affordability, oral bioavailability, broad spectrum of activity, and safety profile. This triazole drug targets lanosterol 14α-demethylase, Erg11, an enzyme that catalyzes the conversion of lanosterol to ergosterol, whose inhibition arrests cell growth by causing the accumulation of toxic sterols and depletion of ergosterol, which together compromise membrane integrity. Iron overload has been shown to promote fungal growth and is considered a significant risk factor for IFIs. Preliminary results from our laboratory suggest that iron-loading conditions reduce the antifungal activity of fluconazole against Candida glabrata, the second most prevalent cause of these infections.(...)"