Iron homeostasis—Achilles’ heel of Aspergillus fumigatus?

Highlights

• Aspergillus fumigatus uses extracellular siderophores for uptake and intracellular siderophores for storage and trafficking of iron. • Intracellular siderophore-mediated iron handling is important for germination, development, and antioxidative defense. • Extra- and intracellular siderophores are crucial for virulence of A. fumigatus and a variety of other fungal species. • The regulator HapX mediates adaptation to iron starvation by activating iron uptake and repressing iron consumption. • HapX is crucial for virulence of A. fumigatus and a variety of other fungal species.

Abstract

The opportunistic fungal pathogen Aspergillus fumigatus adapts to iron limitation by upregulation of iron uptake mechanisms including siderophore biosynthesis and downregulation of iron-consuming pathways to spare iron. These metabolic changes depend mainly on the transcription factor HapX. Consistent with the crucial role of iron in pathophysiology, genetic inactivation of either HapX or the siderophore system attenuates virulence of A. fumigatus in a murine model of aspergillosis. The differences in iron handling between mammals and fungi might serve to improve therapy and diagnosis of fungal infections.