title: Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence.
abstract: 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 DeltapkaR 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, P.O. Box 670529, Cincinnati, Ohio 45267-0529, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: John C
authors.initials: JC
authors.lastname: Panepinto
authors.forename: Jarrod R
authors.initials: JR
authors.lastname: Fortwendel
authors.forename: Lauren
authors.initials: L
authors.lastname: Fox
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
authors.forename: David S
authors.initials: DS
authors.lastname: Askew
authors.forename: Judith C
authors.initials: JC
authors.lastname: Rhodes
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology / Q000401:mortality; D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response; D051379:Mice; D018384:Oxidative Stress; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D017868:Cyclic AMP-Dependent Protein Kinases