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Infection and Immunity, August 2006, p. 4865-4874, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00565-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Deletion of the Regulatory Subunit of Protein Kinase A in Aspergillus fumigatus Alters Morphology, Sensitivity to Oxidative Damage, and Virulence

Wei Zhao, John C. Panepinto, Jarrod R. Fortwendel, Lauren Fox, Brian G. Oliver, David S. Askew, and Judith C. Rhodes*

Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529

Received 5 April 2006/ Returned for modification 28 April 2006/ Accepted 26 May 2006

Aspergillus fumigatus is an important opportunistic fungal pathogen. The cAMP-dependent protein kinase (PKA) signaling pathway plays an important role in regulating morphology, growth, and virulence in a number of fungal pathogens of plants and animals. We have constructed a mutant of A. fumigatus that lacks the regulatory subunit of PKA, pkaR, and analyzed the growth and development, sensitivity to oxidative damage, and virulence of the mutant, along with those of the wild type and a complemented mutant. Both growth and germination rates of the mutant are reduced, and there are morphological abnormalities in conidiophores, leading to reduced conidiation. Conidia from the {Delta}pkaR mutant are more sensitive to killing by hydrogen peroxide, menadione, paraquat, and diamide. However, the hyphae of the mutant are killed to a greater extent only by paraquat and diamide, whereas they are less susceptible to the effects of hydrogen peroxide. In an immunosuppressed mouse model, intranasally administered conidia of the mutant are significantly less virulent than those of the wild type or a complemented mutant. Unregulated PKA signaling is detrimental to the virulence of A. fumigatus, perhaps through the reduced susceptibility of the mutant to damage by oxidizing agents and reduced growth kinetics.

* Corresponding author. Mailing address: Department of Pathology, University of Cincinnati, P.O. Box 670529, Cincinnati, OH 45267-0529. Phone: (513) 558-0130. Fax: (513) 558-2141. E-mail: judith.rhodes{at}uc.edu.

Editor: A. Casadevall

Infection and Immunity, August 2006, p. 4865-4874, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00565-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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