Hemoglobin regulates expression of an activator of mating-type locus alpha genes in Candida albicans.
Phenotypic switching from the white to the opaque phase is a necessary step for mating in the pathogenic fungus Candida albicans. Suppressing switching during vascular dissemination of the organism may be advantageous, because opaque cells are more susceptible to host defenses. A repressor of white-opaque switching, HBR1 (hemoglobin response gene 1), was identified based on its specific induction following growth in the presence of exogenous hemoglobin. Deletion of a single HBR1 allele allowed opaque phase switching and mating competence, accompanied by a lack of detectable MTL alpha1 and alpha2 gene expression and enhanced MTLa1 gene expression. Conversely, overexpression of Hbr1p or exposure to hemoglobin increased MTLalpha gene expression. The a1/alpha2 repressed target gene CAG1 was derepressed in the same mutant in a hemoglobin-sensitive manner. Regulation of CAG1 by hemoglobin required an intact MTLa1 gene. Several additional Mtlp targets were perturbed in HBR1 mutants in a manner consistent with commitment to an a mating phenotype, including YEL007w, MFalpha, HST6, and RAM2. Therefore, Hbr1 is part of a host factor-regulated signaling pathway that controls white-opaque switching and mating in the absence of allelic deletion at the MTL locus.
Pendrak
Michael L
ML
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA. droberts@helix.nih.gov
Yan
S Steve
SS
Roberts
David D
DD
D000483:Alleles; D000595:Amino Acid Sequence; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D049770:Genes, Mating Type, Fungal; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D017931:DNA Primers; D005656:Fungal Proteins; D006454:Hemoglobins; C074148:CAG1 protein, Candida albicans; D019204:GTP-Binding Proteins