The interplay between zinc and iron homeostasis in <i>Aspergillus fumigatus</i> under zinc‐replete conditions relies on the iron‐mediated regulation of alternative transcription units of <i>zafA</i> and the basal amount of the ZafA zinc‐responsiveness transcription factor

Abstract

ions from living tissues, which is induced by the ZafA transcription factor. This study shows that the ZafA-mediated regulation of fungal growth is also influenced by iron availability and that A. fumigatus is well adapted to grow in zinc-limiting and zinc-replete media with Zn:Fe ratios lower in the former than in the latter. Accordingly, this indicates that iron availability appears to be more critical for fungal growth in zinc-replete than in zinc-limiting environments. Interestingly, the cross-regulation of zinc/iron homeostasis under zinc-replete conditions relies on an unprecedented iron-mediated regulation of different zafA transcription units that, along with a limited transcript translation, allows synthesizing the right basal amount of ZafA dependent on iron availability. We posit that this regulatory strategy has evolved in fungi as a mechanism to adjust zinc intake to iron availability under zinc-replete conditions. Thus, fungal growth is enhanced in zinc- and iron-replete media but restricted by reducing zinc intake under iron starvation to prevent the noxious side effects of an intracellular zinc excess during iron deficiency.