title: Aspergillus cyclooxygenase-like enzymes are associated with prostaglandin production and virulence.
abstract: 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 H(2)O(2) 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.
authors.affiliation: Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Tsitsigiannis
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Bok
authors.forename: David
authors.initials: D
authors.lastname: Andes
authors.forename: Kristian Fog
authors.initials: KF
authors.lastname: Nielsen
authors.forename: Jens C
authors.initials: JC
authors.lastname: Frisvad
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000201:enzymology; D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000472:pathogenicity; D001233:Aspergillus nidulans / Q000201:enzymology* / Q000472:pathogenicity; D008172:Lung Diseases, Fungal / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014774:Virulence / Q000502:physiology
chemical_list: D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases