Defects in conidiophore development and conidial/macrophage interactions in a dioxygenase mutant of Aspergillus fumigatus

Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI, U.S.A.; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, U.S.A.; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, U.S.A.; Department of Medicine, University of Wisconsin-Madison, Madison, WI, U.S.A.

^* To whom correspondence should be addressed. Email: npk{at}plantpath.wisc.edu.

	Abstract

Oxygenated fatty acids, or oxylipins, play an essential role in physiological signaling and developmental processes in animals, plants and fungi. Previous characterization of three A. fumigatus dioxygenases (PpoA, PpoB, PpoC), similar in sequence to mammalian cyclooxygenases, showed PpoA responsible for production of the oxylipins 8R-hydroperoxyoctadecadienoic acid (8R-HPODE) and 5S,8R-dihydroxy-9Z,12Z-octadecadienoic acid (5S,8R-DiHODE) and PpoC for 10R-hydroxy-8E,12Z-hydroperoxyoctadecadienoic acid (10R-H(P)ODE). Here, ppo mutants were characterized to elucidate the role of fungal dioxygenases in A. fumigatus development and host interactions. The ppoC strain displayed distinct phenotypes compared to other ppo mutants and wild type, including altered conidia size, germination, and tolerance to oxidative stress as well as increased uptake and killing by primary alveolar macrophages. These experiments implicate oxylipins in pathogen development and suggest that ppoC represents a useful model for studying the A. fumigatus/host interaction.