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

Markus Schrettl, Elaine Bignell, Claudia Kragl, Chistoph Joechl, Tom Rogers, Herbert N. Arst, Ken Haynes, Hubertus Haas

    Research output: Contribution to journalArticlepeer-review

    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-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.
    Original languageEnglish
    Pages (from-to)1213-1219
    Number of pages6
    JournalJournal of Experimental Medicine
    Volume200
    Issue number9
    DOIs
    Publication statusPublished - 1 Nov 2004

    Keywords

    • Aspergillosis
    • Fungal pathogenicity
    • Iron uptake
    • Ornithine monooxygenase
    • Virulence factor

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