title: Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus.
abstract: Aspergillus fumigatus is an important opportunistic fungal pathogen that is responsible for high mortality rates in the immunosuppressed population. CgrA, the A. fumigatus ortholog of a Saccharomyces cerevisiae nucleolar protein involved in ribosome biogenesis, contributes to the virulence of this fungus by supporting rapid growth at 37 degrees C. To determine how CgrA affects ribosome biogenesis in A. fumigatus, polysome profile and ribosomal subunit analyses were performed on both wild-type A. fumigatus and a DeltacgrA mutant. The loss of CgrA was associated with a reduction in the level of 80S monosomes as well as an imbalance in the 60S:40S subunit ratio and the appearance of half-mer ribosomes. The gene expression profile in the DeltacgrA mutant revealed increased abundance of a subset of translational machinery mRNAs relative to the wild type, suggesting a potential compensatory response to CgrA deficiency. Although DeltacgrA conidia germinated normally at 22 degrees C, they swelled excessively when incubated at 37 degrees C and accumulated abnormally high numbers of nuclei. This hypernucleated phenotype could be replicated pharmacologically by germinating wild-type conidia under conditions of reductive stress. These findings indicate that the germination process is particularly vulnerable to global disruption of protein synthesis and suggest that CgrA is involved in both ribosome biogenesis and polarized cell growth in A. fumigatus.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bhabhra
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Richie
authors.forename: H Stanley
authors.initials: HS
authors.lastname: Kim
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
authors.forename: Jarrod
authors.initials: J
authors.lastname: Fortwendel
authors.forename: John P
authors.initials: JP
authors.lastname: Aris
authors.forename: Judith C
authors.initials: JC
authors.lastname: Rhodes
authors.forename: David S
authors.initials: DS
authors.lastname: Askew
mesh_terms: D001232:Aspergillus fumigatus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011132:Polyribosomes; D016601:RNA-Binding Proteins; D012270:Ribosomes / Q000378:metabolism*; D013172:Spores, Fungal / Q000254:growth & development
chemical_list: C433726:CGRA protein, Aspergillus fumigatus; D005656:Fungal Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins