Siderophore Biosynthesis But Not Reductive Iron Assimilation Is Essential for<i>Aspergillus fumigatus</i>Virulence

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  • Markus Schrettl
    1Department of Molecular Biology, Medical University Innsbruck, Peter-Mayr-Str. 4b/III, A-6020 Innsbruck, Austria
  • Elaine Bignell
    2Department of Infectious Diseases, Imperial College London, London W12 0NN, England, UK
  • Claudia Kragl
    1Department of Molecular Biology, Medical University Innsbruck, Peter-Mayr-Str. 4b/III, A-6020 Innsbruck, Austria
  • Chistoph Joechl
    1Department of Molecular Biology, Medical University Innsbruck, Peter-Mayr-Str. 4b/III, A-6020 Innsbruck, Austria
  • Tom Rogers
    2Department of Infectious Diseases, Imperial College London, London W12 0NN, England, UK
  • Herbert N. Arst
    2Department of Infectious Diseases, Imperial College London, London W12 0NN, England, UK
  • Ken Haynes
    2Department of Infectious Diseases, Imperial College London, London W12 0NN, England, UK
  • Hubertus Haas
    1Department of Molecular Biology, Medical University Innsbruck, Peter-Mayr-Str. 4b/III, A-6020 Innsbruck, Austria

説明

<jats:p>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.</jats:p>

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