Siderophore Biosynthesis But Not Reductive Iron
Assimilation |
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http://www.jem.org/cgi/content/abstract/jem.20041242v1
Brief Definitive Report
Siderophore Biosynthesis But Not Reductive Iron Assimilation Is
Essential for Aspergillus fumigatus Virulence
Markus Schrettl1, Elaine Bignell2, Claudia Kragl1, Chistoph Joechl1, Tom
Rogers2, Herbert N. Arst, Jr.2, Ken Haynes2, and Hubertus Haas1
1 Department of Molecular Biology, Medical University Innsbruck, Peter-Mayr-Str.
4b/III, A-6020 Innsbruck, Austria
2 Department of Infectious Diseases, Imperial College London, London W12
0NN, England, UK
Address correspondence to Hubertus Haas, Dept. of Molecular Biology,
Medical University Innsbruck, Peter-Mayr-Str. 4b/III, A-6020 Innsbruck,
Austria. Phone: 43-512-507-3605; Fax: 43-512-507-9880; email:
hubertus.haas@uibk.ac.at
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-N 5-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. |
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