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Eukaryotic Cell, July 2008, p. 1168-1179, Vol. 7, No. 7
1535-9778/08/$08.00+0     doi:10.1128/EC.00108-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors{triangledown}

Yong-Un Baek,1 Mingchun Li,1,2 and Dana A. Davis1*

Department of Microbiology, The University of Minnesota, Minneapolis, Minnesota 55455,1 Laboratory of Molecular Microbiology and Technology, Department of Microbiology, Nankai University, Tianjin, China 3000712

Received 25 March 2008/ Accepted 9 May 2008

Iron is an essential nutrient that is severely limited in the mammalian host. Candida albicans encodes a family of 15 putative ferric reductases, which are required for iron acquisition and utilization. Despite the central role of ferric reductases in iron acquisition and mobilization, relatively little is known about the regulatory networks that govern ferric reductase gene expression in C. albicans. Here we have demonstrated the differential regulation of two ferric reductases, FRE2 and FRP1, in response to distinct iron-limited environments. FRE2 and FRP1 are both induced in alkaline-pH environments directly by the Rim101 transcription factor. However, FRP1 but not FRE2 is also induced by iron chelation. We have identified a CCAAT motif as the critical regulatory sequence for chelator-mediated induction and have found that the CCAAT binding factor (CBF) is essential for FRP1 expression in iron-limited environments. We found that a hap5{Delta}/hap5{Delta} mutant, which disrupts the core DNA binding activity of CBF, is unable to grow under iron-limited conditions. C. albicans encodes three CBF-dependent transcription factors, and we identified the Hap43 protein as the CBF-dependent transcription factor required for iron-limited responses. These studies provide key insights into the regulation of ferric reductase gene expression in the fungal pathogen C. albicans.


* Corresponding author. Mailing address: University of Minnesota, 1360 Mayo Building MMC196, 420 Delaware St., Minneapolis, MN 55455. Phone: (612) 624-1912. Fax: (612) 626-0623. E-mail: dadavis{at}umn.edu

{triangledown} Published ahead of print on 23 May 2008.


Eukaryotic Cell, July 2008, p. 1168-1179, Vol. 7, No. 7
1535-9778/08/$08.00+0     doi:10.1128/EC.00108-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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