VIB general meeting location:Blankenberge date:1-2 March 2007
The level of glucose in human blood oscillates between 4 and 8mM, and can go higher after a meal. At a concentration of 5mM or less, the human pathogen Candida albicans starts filamenting in in vitro systems, whereas in higher concentrations it multiplies as yeast form only. Mechanisms of transport and sensing of glucose probably indirectly influence morphogenesis. It is known that the switch between the various morphogenetic forms is critical for virulence and dissemination in in vivo models. Hence our interest focuses on the relationship and mode of action between glucose, glucose senors and/or transporters and the downstream effectors that are virulence, biofilm formation, or adhesion. We are focusing on 3 distinct trans-membrane proteins, namely Gpr1, Hgt4 and Hgt12. We have shown that Gpr1 is involved in invasive growth and virulence, but it is not involved in hyphal growth per se. Hgt4 has been characterized as a high affinity glucose sensor (Brown et al., 2006), while Hgt12 is certainly a high affinity glucose transporter. Neither of these three proteins is essential for growth on glucose. Even at low sugar concentrations, strains carrying deletion in one of these receptors can grow. However, it seems that deletion of Gpr1 or Hgt4 leads to defect in glucose-induced filamentation. Establishing the glucose signaling network and consecutive influence on fungal virulent development has interesting potential applications in finding new drug targets.