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Eukaryotic Cell, September 2005, p. 1574-1582, Vol. 4, No. 9
1535-9778/05/$08.00+0     doi:10.1128/EC.4.9.1574-1582.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

LaeA, a Regulator of Morphogenetic Fungal Virulence Factors{dagger}

Jin Woo Bok,1,{ddagger} S. Arunmozhi Balajee,2,{ddagger} Kieren A. Marr,2,3 David Andes,1 Kristian Fog Nielsen,4 Jens C. Frisvad,4 and Nancy P. Keller1*

University of Wisconsin—Madison, Madison, Wisconsin,1 Fred Hutchinson Cancer Research Center,2 University of Washington, Seattle, Washington,3 Center for Microbial Biotechnology, Technical University of Denmark, Lyngby, Denmark4

Received 2 February 2005/ Accepted 13 June 2005

Opportunistic animal and plant pathogens, well represented by the genus Aspergillus, have evolved unique mechanisms to adapt to and avoid host defenses. Aspergillus fumigatus, an increasingly serious pathogen owing to expanding numbers of immunocompromised patients, causes the majority of human infections; however, an inability to identify bona fide virulence factors has impeded therapeutic advances. We show that an A. fumigatus mutation in a developmentally expressed transcriptional regulator ({Delta}laeA) coordinating morphological and chemical differentiation reduces virulence in a murine model; impaired virulence is associated with decreased levels of pulmonary gliotoxin and multiple changes in conidial and hyphal susceptibility to host phagocytes ex vivo. LaeA, a conserved protein in filamentous fungi, is a developmental regulator of virulence genes and, possibly, the first antimicrobial target specific to filamentous fungi that are pathogenic to plants and animals.

* Corresponding author. Mailing address: Univ. of Wisconsin—Madison, Department of Plant Pathology, 882 Russell Labs, 1630 Linden Drive, Madison, WI 53706. Phone: (608) 265-9795. Fax: (608) 263-2626. E-mail: npk{at}plantpath.wisc.edu.

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

{ddagger} These authors contributed equally to this work.

Eukaryotic Cell, September 2005, p. 1574-1582, Vol. 4, No. 9
1535-9778/05/$08.00+0     doi:10.1128/EC.4.9.1574-1582.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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