Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence.

Markus Schrettl1, Elaine Bignell2, Claudia Kragl1, Chistoph Jöchl1, Tom Rogers2, Herbert N. Arst Jr2, Ken Haynes2 and Hubertus Haas1.

Author address: 

1Department of Molecular Biology, Medical University Innsbruck, Austria; 2Department of Infectious Diseases, Imperial College London, UK.

Abstract: 

The ability to acquire iron in vivo is essential for most microbial pathogens. Here we show that Aspergillus fumigatus does not have specific mechanisms for the utilization of host iron sources. However, it does have functional siderophore-assisted iron mobilization and reductive iron assimilation systems, both of which are induced upon iron deprivation. Abrogation of reductive iron assimilation, by inactivation of the high-affinity iron permease (FtrA), has no effect on virulence in a murine model of invasive aspergillosis. In striking contrast, A. fumigatus L-ornithine-N5-monooxygenase (SidA), which catalyses the first committed step of hydroxamate-type siderophore biosynthesis, is absolutely essential for virulence. Thus, A. fumigatus SidA is an essential virulence attribute. Combined with the absence of a sidA ortholog - and the fungal siderophore system in general - in mammals, these data demonstrate that the siderophore biosynthetic pathway represents a promising new target for the development of antifungal therapies. This work was supported by the Austrian Science Foundation), the Chronic Granulomatous Disorder Research Trust and the Biotechnological and Biological Sciences Research Council.
2005

abstract No: 

273

Full conference title: 

23rd Fungal Genetics Conference
    • Fungal Genetics Conference 23rd (2002)