Persister cells of C. albicans are committed to energy storage.

Several enzymes of energy storage pathways are up-regulated in persister cells (indicated in green), whereas glycolysis is down-regulated (indicated in red), suggesting that C. albicans persister cells are adapted to the absence of glucose. Icl1 and Mls1 are up-regulated in persister cells. This results in an increase in oxaloacetate that enters gluconeogenesis that is converted to phophoenolpyruvate by Pck1. Pck1, together with Fbp1, are also up-regulated in persister cells and are both key enzymes in the gluconeogenesis pathway. The up-regulation of these enzymes will likely result in an increased flux towards the production of energy storage molecules such as trehalose and glycogen. Additionally, up-regulation of Fbp1 also results in a decreased amount of fructose-1,6-biphosphate, which is the activator of Ras1. This suggests that persister cells have a lower proportion of active Ras1. Finally, Hsp90, which is up-regulated in persister cells may also inhibit the activation of Ras1 in persister cells. Ras1 is up-regulated in persister cells, and because persister cells appear to have a lower proportion of active Ras1, this may prepare persister cells for a rapid metabolic switch to restart proliferation. Dashed bold lines: likely to occur in persister cells; bold lines: proven in persister cells; dashed lines: likely to occur in cells growing in the presence of glucose. All other lines: proven to occur in cells growing in the presence of glucose. Fbp1, fructose-1,6-biphosphatase; GDP, guanosine-5'-diphosphate; GTP, guanosine-5'-triphosphate; Hsp90, heat shock protein 90;Icl1, Isocitrate lysase; Mls1, malate synthase; Pck1, phosphoenolpyruvate carboxykinase; Ras1, rat sarcoma.