Onderzoek naar de rol van 2-deoxyglucose-6-fosfaatfosfatasen in Saccharomyces cerevisiae en Candida albicans

DOG genes, which encode for 2-deoxyglucose 6-phosphate phosphatases, belong to the Haloacid dehalogenase (HAD) superfamily and are known to utilize the non-natural 2-deoxyglucose-6-phosphate (a derivative of 2-DG) as their substrate. However, their physiological substrate is not known, and hence their biological role remains elusive. These genes are upregulated under various environmental stress conditions, such as osmotic, salt, cell wall, heat, oxidative, and phosphate starvation stress. However, the precise mechanism by which they respond to these stressors remains unclear. In Saccharomyces cerevisiae, we have shown that overexpression of the DOG genes restore the osmotic and ionic stress tolerance without the need to biosynthesize glycerol or utilizing glycerol-3 phosphate (Gly-3P) or dihydroxyacetone phosphate (DHAP) as substrates. This challenges the proposed existence of a novel glycerol biosynthetic pathway in yeast. Upon performing expression analysis of DOG1 and DOG2 in S. cerevisiae, preliminary data revealed co-regulation with Pho84, a high-affinity phosphate transporter. Subsequently, in the fungal pathogen Candida albicans, the phenotype of the dog1Δ/Δ pho84Δ/Δ double mutant under various stress conditions, such as phosphate stress, cell wall stress, and ionic stress, displayed higher sensitivity as compared to the individual mutants, dog1Δ/Δ and pho84Δ/Δ. These findings suggest that DOG1 and PHO84 likely act in parallel to mitigate stress in C. albicans, potentially by facilitating phosphate acquisition under various environmental stress conditions. Additionally, this study screens various transcription factors that may regulate DOG1 expression in C. albicans. Hence, this work provides valuable insights into the role of DOG genes in modulating phosphate homeostasis during cell wall stress and phosphate deprivation.