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Infection and Immunity, September 2005, p. 5493-5503, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5493-5503.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Aspergillus fumigatus Siderophore Biosynthetic Gene sidA, Encoding L-Ornithine N5-Oxygenase, Is Required for Virulence

Anna H. T. Hissen, Adrian N. C. Wan, Mark L. Warwas, Linda J. Pinto, and Margo M. Moore*

Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada

Received 21 September 2004/ Returned for modification 20 October 2004/ Accepted 5 May 2005

Aspergillus fumigatus is the leading cause of invasive mold infection and is a serious problem in immunocompromised populations worldwide. We have previously shown that survival of A. fumigatus in serum may be related to secretion of siderophores. In this study, we identified and characterized the sidA gene of A. fumigatus, which encodes L-ornithine N5-oxygenase, the first committed step in hydroxamate siderophore biosynthesis. A. fumigatus sidA codes for a protein of 501 amino acids with significant homology to other fungal L-ornithine N5-oxygenases. A stable {Delta}sidA strain was created by deletion of A. fumigatus sidA. This strain was unable to synthesize the siderophores N',N",N'''-triacetylfusarinine C (TAF) and ferricrocin. Growth of the {Delta}sidA strain was the same as that of the wild type in rich media; however, the {Delta}sidA strain was unable to grow in low-iron defined media or media containing 10% human serum unless supplemented with TAF or ferricrocin. No significant differences in ferric reduction activities were observed between the parental strain and the {Delta}sidA strain, indicating that blocking siderophore secretion did not result in upregulation of this pathway. Unlike the parental strain, the {Delta}sidA strain was unable to remove iron from human transferrin. A rescued strain ({Delta}sidA + sidA) was constructed; it produced siderophores and had the same growth as the wild type on iron-limited media. Unlike the wild-type and rescued strains, the {Delta}sidA strain was avirulent in a mouse model of invasive aspergillosis, indicating that sidA is necessary for A. fumigatus virulence.

* Corresponding author. Mailing address: Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. Phone: (604) 291-3441. Fax: (604) 291-3496. E-mail: mmoore{at}sfu.ca.

Editor: T. R. Kozel

Infection and Immunity, September 2005, p. 5493-5503, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5493-5503.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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