Iron is an essential element for all eukaryotes but its excess is deleterious. Iron homeostasis results from tight regulation of iron acquisition and iron storage. A. fumigatus produces the extracellular siderophores triacetylfusarinine C (TAFC) and fusarinine C (FSC) for iron uptake and the intracellular siderophores ferricrocin (FC) and hydroxyferricrocin for iron distribution and storage. Siderophore biosynthesis is important for the adaptation to iron starvation and therefore crucial for virulence. Intracellular iron excess has been shown to increase the content of FC-chelated iron and the expression of AFUA_4g12530, termed CccA, which shows similarity to the vacuolar iron importer Ccc1 of S. cerevisiae. These data indicate a role of both the vacuole and FC in iron detoxification. Green fluorescence protein-tagging confirmed localization of CccA in the vacuolar membrane. During high iron conditions genetic inactivation of CccA impaired growth, in particular in combination with derepressed iron uptake due to deficiency in the iron regulator SreA. In contrast, overproduction of CccA increased iron resistance. Inactivation of FC biosynthesis did not affect iron resistance. Lack of FC, CccA and in particular both, increased the cellular content of iron chelated by FSC/TAFC breakdown products. A delayed release of iron from FSC/TAFC degradation products might represent another iron detoxifying mechanism. Our data indicate that vacuolar rather than FC-mediated iron storage is the major iron detoxifying mechanism of A. fumigatus.
Full conference title:
- Asperfest 9 (2012)