Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus (original) (raw)

Aspergillus fumigatus is the most common airborne fungal pathogen for humans. Iron starvation induces the production of the siderophore triacetylfusarinine C (TAFC). This study demonstrates a link between TAFC and ergosterol biosynthetic pathways, critical for virulence and treatment of fungal infections. Mevalonate was found to be a limiting factor for TAFC biosynthesis, as increased expression of HMG-CoA reductase was observed under iron starvation, while inhibition of this enzyme reduced TAFC biosynthesis. Key enzymes connecting mevalonate and TAFC biosynthesis were identified, and the absence of these enzymes impaired growth, virulence, and oxidative stress resistance. The interplay between iron starvation, taferh and ergosterol synthesis further highlights the potential for therapeutic interventions targeting these pathways.