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Eukaryotic Cell, October 2006, p. 1726-1737, Vol. 5, No. 10
1535-9778/06/$08.00+0     doi:10.1128/EC.00186-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Glucose Sensor in Candida albicans{dagger}

Victoria Brown,* Jessica A. Sexton, and Mark Johnston

Department of Genetics, Center for Genome Sciences, Washington University School of Medicine, 4444 Forest Park Blvd., Rm. 5401, Campus Box 8510, St. Louis, Missouri 63108

Received 15 June 2006/ Accepted 26 July 2006

The Hgt4 protein of Candida albicans (orf19.5962) is orthologous to the Snf3 and Rgt2 glucose sensors of Saccharomyces cerevisiae that govern sugar acquisition by regulating the expression of genes encoding hexose transporters. We found that HGT4 is required for glucose induction of the expression of HGT12, HXT10, and HGT7, which encode apparent hexose transporters in C. albicans. An hgt4{Delta} mutant is defective for growth on fermentable sugars, which is consistent with the idea that Hgt4 is a sensor of glucose and similar sugars. Hgt4 appears to be sensitive to glucose levels similar to those in human serum (~5 mM). HGT4 expression is repressed by high levels of glucose, which is consistent with the idea that it encodes a high-affinity sugar sensor. Glucose sensing through Hgt4 affects the yeast-to-hyphal morphological switch of C. albicans cells: hgt4{Delta} mutants are hypofilamented, and a constitutively signaling form of Hgt4 confers hyperfilamentation of cells. The hgt4{Delta} mutant is less virulent than wild-type cells in a mouse model of disseminated candidiasis. These results suggest that Hgt4 is a high-affinity glucose sensor that contributes to the virulence of C. albicans.

* Corresponding author. Mailing address: Department of Genetics, Center for Genome Sciences, Washington University School of Medicine, 4444 Forest Park Blvd., Rm. 5401, Campus Box 8510, St. Louis, MO 63108. Phone: (314) 362-5799. Fax: (314) 362-2156. E-mail: vbrownk{at}genetics.wustl.edu.

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

Eukaryotic Cell, October 2006, p. 1726-1737, Vol. 5, No. 10
1535-9778/06/$08.00+0     doi:10.1128/EC.00186-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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