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Eukaryotic Cell, April 2008, p. 575-583, Vol. 7, No. 4
1535-9778/08/$08.00+0     doi:10.1128/EC.00412-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Impaired Ribosome Biogenesis Disrupts the Integration between Morphogenesis and Nuclear Duplication during the Germination of Aspergillus fumigatus

Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0529,¹ Department of Medicine, College of Medicine, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-705, Korea,² J. Craig Venter Institute, Rockville, Maryland 20850,³ The George Washington University School of Medicine and Health Sciences, Washington, DC 20037,⁴ Department of Anatomy and Cell Biology, University of Florida Health Sciences Center, Gainesville, Florida 32610-0235⁵

Received 9 November 2007/ Accepted 11 February 2008

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 cgrA 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 cgrA 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 cgrA 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.

Published ahead of print on 22 February 2008.