Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus

Ruchi Bhabhra, Daryl L. Richie, H. Stanley Kim, William C. Nierman, Jarrod Fortwendel, John P. Aris, Judith C. Rhodes, David S. Askew

Research output: Contribution to journalArticle

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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°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 ΔcgrA 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 ΔcgrA 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 ΔcgrA conidia germinated normally at 22°C, they swelled excessively when incubated at 37°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.

Original languageEnglish (US)
Pages (from-to)575-583
Number of pages9
JournalEukaryotic Cell
Volume7
Issue number4
DOIs
StatePublished - Apr 1 2008

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Aspergillus fumigatus
Germination
ribosomes
Ribosomes
Morphogenesis
morphogenesis
germination
Fungal Spores
conidia
Saccharomyces cerevisiae Proteins
Ribosome Subunits
mutants
polyribosomes
Polyribosomes
Growth
Nuclear Proteins
Transcriptome
Virulence
cell growth
Saccharomyces cerevisiae

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Microbiology

Cite this

Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus. / Bhabhra, Ruchi; Richie, Daryl L.; Kim, H. Stanley; Nierman, William C.; Fortwendel, Jarrod; Aris, John P.; Rhodes, Judith C.; Askew, David S.

In: Eukaryotic Cell, Vol. 7, No. 4, 01.04.2008, p. 575-583.

Research output: Contribution to journalArticle

Bhabhra, Ruchi ; Richie, Daryl L. ; Kim, H. Stanley ; Nierman, William C. ; Fortwendel, Jarrod ; Aris, John P. ; Rhodes, Judith C. ; Askew, David S. / Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus. In: Eukaryotic Cell. 2008 ; Vol. 7, No. 4. pp. 575-583.
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