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Eukaryotic Cell, October 2007, p. 1876-1888, Vol. 6, No. 10
1535-9778/07/$08.00+0     doi:10.1128/EC.00039-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Histatin 5 Initiates Osmotic Stress Response in Candida albicans via Activation of the Hog1 Mitogen-Activated Protein Kinase Pathway{triangledown}

Slavena Vylkova,1 Woong Sik Jang,1 Wansheng Li,1,3 Namrata Nayyar,1 and Mira Edgerton1,2*

Departments of Oral Biology,1 Restorative Dentistry, School of Dental Medicine,2 Department of Biostatistics, School of Public Health and Health Professions, State University of New York at Buffalo, Buffalo, New York 142143

Received 1 February 2007/ Accepted 27 July 2007

Histatin 5 (Hst 5) is a salivary cationic peptide that has toxicity for Candida albicans by inducing rapid cellular ion imbalance and cell volume loss. Microarray analyses of peptide-treated cells were used to evaluate global gene responses elicited by Hst 5. The major transcriptional response of C. albicans to Hst 5 was expression of genes involved in adaptation to osmotic stress, including production of glycerol (RHR2, SKO1, and PDC11) and the general stress response (CTA1 and HSP70). The oxidative-stress genes AHP1, TRX1, and GPX1 were mildly induced by Hst 5. Cell defense against Hst 5 was dependent on the Hog1 mitogen-activated protein kinase (MAPK) pathway, since C. albicans hog1/hog1 mutants were significantly hypersensitive to Hst 5 but not to Mkc1 MAPK or Cek1 MAPK mutants. Activation of the high-osmolarity glycerol (HOG) pathway was demonstrated by phosphorylation of Hog1 MAPK as well as by glycerol production following Hst 5 treatment in a dose-dependent manner. C. albicans cells prestressed with sorbitol were less sensitive to subsequent Hst 5 treatment; however, cells treated concurrently with osmotic stress and Hst 5 were hypersensitive to Hst 5. In contrast, cells subjected to oxidative stress had no difference in sensitivity to Hst 5. These results suggest a common underlying cellular response to osmotic stress and Hst 5. The HOG stress response pathway likely represents a significant and effective challenge to physiological levels of Hst 5 and other toxic peptides in fungal cells.


* Corresponding author. Mailing address: 310 Foster Hall, SUNY at Buffalo Main Street Campus, 3435 Main Street, Buffalo, NY 14214. Phone: (716) 829-3067. Fax: (716) 829-3942. E-mail: edgerto{at}buffalo.edu

{triangledown} Published ahead of print on 22 August 2007.


Eukaryotic Cell, October 2007, p. 1876-1888, Vol. 6, No. 10
1535-9778/07/$08.00+0     doi:10.1128/EC.00039-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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