Validation of the sugar kinases as an antifungal drug target in Candida glabrata

The human health is threatened by the emergence of drug resistant fungal species, like Candida glabrata, indicating the need for new antifungal drugs and targets. The central metabolism appears to be tied to the pathogenicity of fungi. This also seems to be the case for C. glabrata’s sugar metabolism. Nevertheless, C. glabrata is an odd fungus concerning its sugar metabolism. It can only use glucose and trehalose as fermentable carbon sources despite the presence of gene orthologs for transport and metabolization of other sugars. Interestingly, a high glucose import rate was observed in C. glabrata, while there are only 11 hexose transporters encoded. Did C. glabrata become specialized for glucose transport upon its adaptation to the human host? To investigate this, we will determine the substrate specificity and kinetics of the hexose transporters and compare sugar transport of clinical and environmental isolates. Once sugar is imported, glycolysis takes place. We found five sugar kinases, catalyzing sugar phosphorylation, in C. glabrata. This is surprising as this is more than found in related fungi and they presumably only have glucose as substrate. To gain more knowledge about this, we will determine whether the sugar kinases are able to phosphorylate other sugars and if they have additional roles. Finally, as several virulence-related pathways require sugar phosphorylation, we will look into the effect of this phosphorylation on in vitro, ex vivo and in vivo virulence.