Transcriptional profiling of the Candida albicans Ssk1p receiver domain point mutants and their virulence.
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. We have previously shown that the amino acid residues D556 and D513 of the Ssk1p receiver domain are critical to the Ssk1p in oxidant stress adaptation and morphogenesis. Herein, transcriptional profiling is used to explain the oxidant sensitivity and morphogenesis defect of two point mutants (D556N and D513K, respectively) compared with a WT strain. In the D556N mutant, during oxidative stress (5 mM H(2)O(2)), a downregulation of genes associated with redox homeostasis and oxidative stress occurred, which accounted for about 5% of all gene changes, including among others, SOD1 (superoxide dismutase), CAP1 (required for some types of oxidant stress), and three genes encoding glutathione biosynthesis proteins (GLR1, GSH1, and GSH2). Mutant D513K was not sensitive to peroxide but was impaired in its yeast $/to hyphal transition. We noted downregulation of genes associated with morphogenesis and cell elongation. Virulence of each mutant was also evaluated in a rat vaginitis model of candidiasis. Clearance of an SSK1 null and the D556N mutants from the vaginal canal was significantly greater than wild type or the D513K mutant, indicating that a change in a single amino acid of the Ssk1p alters the ability of this strain to colonize the rat vaginal mucosa.
Menon
Veena
V
Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC 20057, USA.
De Bernardis
Flavia
F
Calderone
Richard
R
Chauhan
Neeraj
N
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D002181:Candidiasis, Vulvovaginal / Q000382:microbiology; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020125:Mutation, Missense / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D017354:Point Mutation; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014621:Vagina / Q000382:microbiology; D014627:Vaginitis / Q000382:microbiology; D014774:Virulence
D000935:Antifungal Agents; D005656:Fungal Proteins; C487633:SSK1 protein, Candida albicans; D006861:Hydrogen Peroxide