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Eukaryotic Cell, October 2006, p. 1585-1595, Vol. 5, No. 10
1535-9778/06/$08.00+0     doi:10.1128/EC.00192-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Upstream and Downstream Regulation of Asexual Development in Aspergillus fumigatus{dagger}

Jae-Hyung Mah1 and Jae-Hyuk Yu1,2*

Department of Food Microbiology and Toxicology and Food Research Institute,1 Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Madison, Wisconsin 537062

Received 19 June 2006/ Accepted 18 July 2006

The opportunistic human pathogen Aspergillus fumigatus produces a large quantity of asexual spores (conidia), which are the primary agent causing invasive aspergillosis in immunocompromised patients. We investigated the mechanisms controlling asexual sporulation (conidiation) in A. fumigatus via examining functions of four key regulators, GpaA (G{alpha}), AfFlbA (RGS), AfFluG, and AfBrlA, previously studied in Aspergillus nidulans. Expression analyses of gpaA, AfflbA, AffluG, AfbrlA, and AfwetA throughout the life cycle of A. fumigatus revealed that, while transcripts of AfflbA and AffluG accumulate constantly, the latter two downstream developmental regulators are specifically expressed during conidiation. Both loss-of-function AfflbA and dominant activating GpaAQ204L mutations resulted in reduced conidiation with increased hyphal proliferation, indicating that GpaA signaling activates vegetative growth while inhibiting conidiation. As GpaA is the primary target of AfFlbA, the dominant interfering GpaAG203R mutation suppressed reduced conidiation caused by loss of AfflbA function. These results corroborate the hypothesis that functions of G proteins and RGSs are conserved in aspergilli. We then examined functions of the two major developmental activators AfFluG and AfBrlA. While deletion of AfbrlA eliminated conidiation completely, null mutation of AffluG did not cause severe alterations in A. fumigatus sporulation in air-exposed culture, implying that, whereas the two aspergilli may have a common key downstream developmental activator, upstream mechanisms activating brlA may be distinct. Finally, both AffluG and AfflbA mutants showed reduced conidiation and delayed expression of AfbrlA in synchronized developmental induction, indicating that these upstream regulators contribute to the proper progression of conidiation.

* Corresponding author. Mailing address: Department of Food Microbiology and Toxicology and Food Research Institute, University of Wisconsin, Madison, Madison, WI 53706. Phone: (608) 262-4696. Fax: (608) 263-1114. E-mail: jyu1{at}wisc.edu.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, October 2006, p. 1585-1595, Vol. 5, No. 10
1535-9778/06/$08.00+0     doi:10.1128/EC.00192-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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