• Medientyp: E-Artikel
  • Titel: 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
  • Beteiligte: Gregori, Christa; Schüller, Christoph; Roetzer, Andreas; Schwarzmüller, Tobias; Ammerer, Gustav; Kuchler, Karl
  • Erschienen: American Society for Microbiology, 2007
  • Erschienen in: Eukaryotic Cell
  • Sprache: Englisch
  • DOI: 10.1128/ec.00106-07
  • ISSN: 1535-9778; 1535-9786
  • Schlagwörter: Molecular Biology ; General Medicine ; Microbiology
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  • Beschreibung: <jats:title>ABSTRACT</jats:title> <jats:p> The high-osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase pathway mediates adaptation to high-osmolarity stress in the yeast <jats:italic>Saccharomyces cerevisiae</jats:italic> . Here we investigate the function of HOG in the human opportunistic fungal pathogen <jats:italic>Candida glabrata. C. glabrata sho1</jats:italic> Δ (Cg <jats:italic>sho1</jats:italic> Δ) deletion strains from the sequenced ATCC 2001 strain display severe growth defects under hyperosmotic conditions, a phenotype not observed for yeast <jats:italic>sho1</jats:italic> Δ mutants. However, deletion of Cg <jats:italic>SHO1</jats:italic> in other genetic backgrounds fails to cause osmostress hypersensitivity, whereas cells lacking the downstream MAP kinase Pbs2 remain osmosensitive. Notably, ATCC 2001 Cg <jats:italic>sho1</jats:italic> Δ cells also display methylglyoxal hypersensitivity, implying the inactivity of the Sln1 branch in ATCC 2001. Genomic sequencing of Cg <jats:italic>SSK2</jats:italic> in different <jats:italic>C. glabrata</jats:italic> backgrounds demonstrates that ATCC 2001 harbors a truncated and mutated Cg <jats:italic>ssk2</jats:italic> - <jats:italic>1</jats:italic> allele, the only orthologue of yeast <jats:italic>SSK2/SSK22</jats:italic> genes. Thus, the osmophenotype of ATCC 2001 is caused by a point mutation in Cg <jats:italic>ssk2</jats:italic> - <jats:italic>1</jats:italic> , which debilitates the second HOG pathway branch. Functional complementation experiments unequivocally demonstrate that HOG signaling in yeast and <jats:italic>C. glabrata</jats:italic> share similar functions in osmostress adaptation. In contrast to yeast, however, Cg <jats:italic>sho1</jats:italic> Δ 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 <jats:italic>C. glabrata</jats:italic> mediates the response to multiple stress conditions. </jats:p>
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