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Science 312 (5773): 583-588

Copyright © 2006 by the American Association for the Advancement of Science

Global Control of Dimorphism and Virulence in Fungi

Julie C. Nemecek,1 Marcel Wüthrich,2 Bruce S. Klein1,2,3,4*

Abstract: Microbial pathogens that normally inhabit our environment can adapt to thrive inside mammalian hosts. There are six dimorphic fungi that cause disease worldwide, which switch from nonpathogenic molds in soil to pathogenic yeast after spores are inhaled and exposed to elevated temperature. Mechanisms that regulate this switch remain obscure. We show that a hybrid histidine kinase senses host signals and triggers the transition from mold to yeast. The kinase also regulates cell-wall integrity, sporulation, and expression of virulence genes in vivo. This global regulator shapes how dimorphic fungal pathogens adapt to the mammalian host, which has broad implications for treating and preventing systemic fungal disease.

1 Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.
2 Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.
3 Department of Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.
4 The Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.

* To whom correspondence should be addressed. E-mail: bsklein{at}

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