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Infection and Immunity, August 2005, p. 4548-4559, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4548-4559.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Aspergillus Cyclooxygenase-Like Enzymes Are Associated with Prostaglandin Production and Virulence

Dimitrios I. Tsitsigiannis ,1,{dagger},{ddagger} Jin-Woo Bok,1,{dagger} David Andes,1 Kristian Fog Nielsen,2 Jens C. Frisvad,2 and Nancy P. Keller1*

University of Wisconsin—Madison, Madison, Wisconsin,1 Center for Microbial Biotechnology, Technical University of Denmark, Lyngby, Denmark2

Received 17 December 2004/ Returned for modification 7 February 2005/ Accepted 3 March 2005

Oxylipins comprise a family of oxygenated fatty acid-derived signaling molecules that initiate critical biological activities in animals, plants, and fungi. Mammalian oxylipins, including the prostaglandins (PGs), mediate many immune and inflammation responses in animals. PG production by pathogenic microbes is theorized to play a role in pathogenesis. We have genetically characterized three Aspergillus genes, ppoA, ppoB, and ppoC, encoding fatty acid oxygenases similar in sequence to specific mammalian prostaglandin synthases, the cyclooxygenases. Enzyme-linked immunosorbent assay analysis showed that production of PG species is decreased in both Aspergillus nidulans and A. fumigatus ppo mutants, implicating Ppo activity in generating PGs. The A. fumigatus triple-ppo-silenced mutant was hypervirulent in the invasive pulmonary aspergillosis murine model system and showed increased tolerance to H2O2 stress relative to that of the wild type. We propose that Ppo products, PG, and/or other oxylipins may serve as activators of mammalian immune responses contributing to enhanced resistance to opportunistic fungi and as factors that modulate fungal development contributing to resistance to host defenses.

* Corresponding author. Mailing address: Department of Plant Pathology, University of Wisconsin—Madison, Madison, WI 53706. Phone: (608) 262-9795. Fax: (608) 263-2626. E-mail: npk{at}plantpath.wisc.edu.

Editor: T. R. Kozel

{dagger} D.I.T. and J.-W.B. contributed equally to this work.

{ddagger} Present address: The Sainsbury Laboratory, John Innes Centre, Norwich Research Park, Colney Lane, Norwich NR4 7UH, United Kingdom.

Infection and Immunity, August 2005, p. 4548-4559, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4548-4559.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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