Abstract
The Ssk1p response regulator of
Candida albicans
is required for oxidant adaptation, survival in human neutrophils, and virulence in a disseminated murine model of candidiasis. The activities of the Ssk1p are signaled through the HOG1 MAP kinase pathway (HOG=
h
yper
o
smotic
g
lycerol). Further, we have previously shown that the amino acid residues D556 and D513 of the Ssk1p receiver domain are critical to the activities of the Ssk1p in oxidant stress adaptation and morphogenesis. Herein, we use transcriptional profiling to explain the oxidant sensitivity and defect in morphogenesis of two point mutants (D556N and D513K, respectively) compared to a WT strain. In the D556N mutant compared to WT cells during oxidative stress (5mM H
2
O
2
), a down regulation of genes associated with redox homeostasis and oxidative stress occurred that accounted for about 5% of all gene changes, including among others,
SOD1
(superoxide dismutase),
CAP1
(transcription factor required for some forms of oxidant adaptation), and three genes encoding glutathione biosynthesis proteins (
GLR1, GSH1, and GSH2
). Mutant SSK26 (D513K) was not sensitive to peroxide but was impaired in its yeast to hyphal transition. We noted down regulation of genes associated with morphogenesis and cell elongation. Virulence of each mutant was also evaluated in a rat vaginitis model of candidiasis. Clearance of the
SSK1
null mutant (strain SSK21) and SSK25 from the vaginal canal was significantly greater than wild type (CAF2-1) or the D513K mutant (D513K), indicating that a specific change in a single amino acid of the Ssk1p may alter the ability of this strain to colonize the rat vaginal mucosa.