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Eukaryotic Cell, February 2008, p. 268-278, Vol. 7, No. 2
1535-9778/08/$08.00+0     doi:10.1128/EC.00240-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

CTA4 Transcription Factor Mediates Induction of Nitrosative Stress Response in Candida albicans{triangledown} ,{dagger}

Wiriya Chiranand,1 Ian McLeod,2 Huaijin Zhou,3 Jed J. Lynn,1 Luis A. Vega,1 Hadley Myers,1 John R. Yates III,2 Michael C. Lorenz,3 and Michael C. Gustin1*

Department of Biochemistry and Cell Biology, Rice University, Houston, Texas,1 Proteomic Mass Spectrometry Lab, Department of Cell Biology, Scripps Research Institute, La Jolla, California,2 Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center, Houston, Texas3

Received 3 July 2007/ Accepted 28 November 2007

This work has identified regulatory elements in the major fungal pathogen Candida albicans that enable response to nitrosative stress. Nitric oxide (NO) is generated by macrophages of the host immune system and commensal bacteria, and the ability to resist its toxicity is one adaptation that promotes survival of C. albicans inside the human body. Exposing C. albicans to NO induces upregulation of the flavohemoglobin Yhb1p. This protein confers protection by enzymatically converting NO to harmless nitrate, but it is unknown how C. albicans is able to detect NO in its environment and thus initiate this defense only as needed. We analyzed this problem by incrementally mutating the YHB1 regulatory region to identify a nitric oxide-responsive element (NORE) that is required for NO sensitivity. Five transcription factor candidates of the Zn(II)2-Cys6 family were then isolated from crude whole-cell extracts by using magnetic beads coated with this DNA element. Of the five, only deletion of the CTA4 gene prevented induction of YHB1 transcription during nitrosative stress and caused growth sensitivity to the NO donor dipropylenetriamine NONOate; Cta4p associates in vivo with NORE DNA from the YHB1 regulatory region. Deletion of CTA4 caused a small but significant decrease in virulence. A CTA4-dependent putative sulfite transporter encoded by SSU1 is also implicated in NO response, but C. albicans ssu1 mutants were not sensitive to NO, in contrast to findings in Saccharomyces cerevisiae. Cta4p is the first protein found to be necessary for initiating NO response in C. albicans.

* Corresponding author. Mailing address: Department of Biochemistry and Cell Biology, Rice University, P.O. Box 1892, Houston, TX 77251-1892. Phone: (713) 348-5158. Fax: (713) 348-5154. E-mail: gustin{at}rice.edu

{triangledown} Published ahead of print on 14 December 2007.

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

Eukaryotic Cell, February 2008, p. 268-278, Vol. 7, No. 2
1535-9778/08/$08.00+0     doi:10.1128/EC.00240-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Coste, A. T., Ramsdale, M., Ischer, F., Sanglard, D. (2008). Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae. Microbiology 154: 1491-1501 [Abstract] [Full Text]  


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