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Eukaryotic Cell, September 2007, p. 1635-1645, Vol. 6, No. 9
1535-9778/07/$08.00+0     doi:10.1128/EC.00106-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The High-Osmolarity Glycerol Response Pathway in the Human Fungal Pathogen Candida glabrata Strain ATCC 2001 Lacks a Signaling Branch That Operates in Baker's Yeast{triangledown}

Christa Gregori,1 Christoph Schüller,2 Andreas Roetzer,2 Tobias Schwarzmüller,1 Gustav Ammerer,2 and Karl Kuchler1*

Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University Vienna,1 Department of Biochemistry and Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria2

Received 4 April 2007/ Accepted 26 June 2007

The high-osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway mediates adaptation to high-osmolarity stress in the yeast Saccharomyces cerevisiae. Here we investigate the function of HOG in the human opportunistic fungal pathogen Candida glabrata. C. glabrata sho1{Delta} (Cgsho1{Delta}) deletion strains from the sequenced ATCC 2001 strain display severe growth defects under hyperosmotic conditions, a phenotype not observed for yeast sho1{Delta} mutants. However, deletion of CgSHO1 in other genetic backgrounds fails to cause osmostress hypersensitivity, whereas cells lacking the downstream MAP kinase Pbs2 remain osmosensitive. Notably, ATCC 2001 Cgsho1{Delta} cells also display methylglyoxal hypersensitivity, implying the inactivity of the Sln1 branch in ATCC 2001. Genomic sequencing of CgSSK2 in different C. glabrata backgrounds demonstrates that ATCC 2001 harbors a truncated and mutated Cgssk2-1 allele, the only orthologue of yeast SSK2/SSK22 genes. Thus, the osmophenotype of ATCC 2001 is caused by a point mutation in Cgssk2-1, which debilitates the second HOG pathway branch. Functional complementation experiments unequivocally demonstrate that HOG signaling in yeast and C. glabrata share similar functions in osmostress adaptation. In contrast to yeast, however, Cgsho1{Delta} mutants display hypersensitivity to weak organic acids such as sorbate and benzoate. Hence, CgSho1 is also implicated in modulating weak acid tolerance, suggesting that HOG signaling in C. glabrata mediates the response to multiple stress conditions.


* Corresponding author. Mailing address: Medical University Vienna, Max F. Perutz Laboratories, Department of Medical Biochemistry, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria. Phone: 43-1-4277-61807. Fax: 43-1-4277-9618. E-mail: karl.kuchler{at}meduniwien.ac.at

{triangledown} Published ahead of print on 6 July 2007.


Eukaryotic Cell, September 2007, p. 1635-1645, Vol. 6, No. 9
1535-9778/07/$08.00+0     doi:10.1128/EC.00106-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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