Regulation of sugar transport and metabolism by the Candida albicans Rgt1 transcriptional repressor.
The ability of the fungal pathogen Candida albicans to cause systemic infections depends in part on the function of Hgt4, a cell surface sugar sensor. The orthologues of Hgt4 in Saccharomyces cerevisiae, Snf3 and Rgt2, initiate a signalling cascade that inactivates Rgt1, a transcriptional repressor of genes encoding hexose transporters. To determine whether Hgt4 functions similarly through the C. albicans orthologue of Rgt1, we analysed Cargt1 deletion mutants. We found that Cargt1 mutants are sensitive to the glucose analogue 2-deoxyglucose, a phenotype probably due to uncontrolled expression of genes encoding glucose transporters. Indeed, transcriptional profiling revealed that expression of about two dozen genes, including multiple HGT genes encoding hexose transporters, is increased in the Cargt1 mutant in the absence of sugars, suggesting that CaRgt1 represses expression of several HGT genes under this condition. Some of the HGT genes (probably encoding high-affinity transporters) are also repressed by high levels of glucose, and we show that this repression is mediated by CaMig1, the orthologue of the major glucose-activated repressor in S. cerevisiae, but not by its paralogue CaMig2. Therefore, CaRgt1 and CaMig1 collaborate to control expression of C. albicans hexose transporters in response to different levels of sugars. We were surprised to find that CaRgt1 also regulates expression of GAL1, suggesting that regulation of galactose metabolism in C. albicans is unconventional. Finally, Cargt1 mutations cause cells to hyperfilament, and suppress the hypofilamented phenotype of an hgt4 mutant, indicating that the Hgt4 glucose sensor may affect filamentation by modulating sugar import and metabolism via CaRgt1.
Sexton
Jessica A
JA
Department of Genetics, Campus Box 8232, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
Brown
Victoria
V
Johnston
Mark
M
D000595:Amino Acid Sequence; D001692:Biological Transport; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000502:physiology*; D020869:Gene Expression Profiling; D008969:Molecular Sequence Data; D010641:Phenotype; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*
D005656:Fungal Proteins; D012097:Repressor Proteins