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
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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
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>