The impact of ornithine and arginine biosynthesis on siderophore production of Aspergillus fumigatus

Ref ID: 18303

Author:

N. Beckmann
, L. Schafferer
, M. Schrettl
, H. Haas

Author address:

Division of Molecular Biology, Biocenter, Innsbruck Medical University,
Austria

Full conference title:

Asperfest 9

Abstract:

The opportunistic fungal pathogen Aspergillus fumigatus produces extracellular siderophores for iron uptake and intracellular
siderophores for storage and distribution of iron. Moreover, A. fumigatus employs a second high-affinity iron acquisition system,
reductive iron assimilation (RIA). Siderophore biosynthesis (SB) but not RIA is essential for virulence. The main precursor of
siderophores, ornithine, can be produced from glutamate in the mitochondria or cytosolic hydrolysis of ornithine-derived arginine.
Here, the impact of inactivation of mitochondrial ornithine biosynthesis (916;argEF mutant lacking N-acetylglutamate kinase/ Nacetylglutamylphosphate reductase) and cytosolic arginine biosynthesis (916;argB mutant lacking ornithine transcarbamoyl transferase)
on siderophore production was studied. Both 916;argEF and 916;argB are arginine auxotrophic. Growth of 916;argEF but not 916;argB is
partially rescued by ornithine supplementation. Blocking RIA by ferrous iron chelation inhibited growth of 916;argEF but not 916;argB.
Siderophore production of 916;argEF decreased while that of 916;argB increased with declining arginine availability. Taken together, these
data indicate that the siderophore system is mainly fueled by mitochondrial rather than cytosolic ornithine production and that
mitochondrial ornithine biosynthesis is feedback inhibited by arginine. In agreement with the SB defect, 916;argEF displayed a
dramatically reduced cellular ornithine content. In contrast, the arginine and polyamine contents were wild type-like, indicating
prioritization of the later two biosynthetic pathways over SB. Consistent with cellular balancing of SB and arginine metabolism,
arginine was recently identified to allosterically activate the ornithine monooxygenase SidA and consequently SB-mediated ornithine
consumption.

Abstract Number: 54)

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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