FEBS advanced lecture course on Human Fungal pathogens edition:1 location:La Colle sur Loup, France date:21-28 May 2005
The ability of the fungal opportunistic pathogen Candida albicans to switch between yeast, pseudohyphal, and hyphal forms is believed to be an important component of its virulence. Morphological changes of C. albicans can be triggered in vitro by a wide variety of factors. The signal transduction pathways that are triggered by these factors have been studied extensively but the mechanisms of sensing for the different triggers are less understood compared to the situation in S. cerevisiae.
Amino acid rich media (e.g., Lee’s medium) are known to induce the morphological transitions in C. albicans. However, the molecular bases for amino acid-mediated morphogenesis are still obscure. We have used various combinations of LEE’s medium and found that methionine is required for hypha induction in the wild type strain. Similar results were obtained in synthetic medium containing low concentrations of glucose (SLD): whereas in absence of methionine C. albicans forms smooth colonies on top of the agar, addition of 16,7 µM (2,5 mg/L) of methionine results in agar invasion and hypha formation in the wild type strain, despite the presence of large concentrations of ammonium in the medium.
Recently the plasma-membrane amino acid sensor Csy1, regulating gene expression of an amino acid permease family, was described. However, it has been shown that methionine does not activate Csy1 in C. albicans. As a possible candidate for a methionine sensor we considered the G-protein coupled receptor Gpr1 which is an upstream component of the cAMP-PKA pathway (see poster J. Serneels). Deletion of GPR1 causes strong defects in true mycelium formation during growth on hypha-inducing media and abolishes ability to invade agar in the presence of methionine though its uptake is not affected in this strain. To investigate further whether the methionine-induced morphogenesis is the result of transport or sensor activation in response to an external signal we constructed a MUP1 deletion strain. MUP1 encodes a high affinity methionine permease. This strain was not able to form mycelium in presence of lower range of methionine concentration (2,5-20 mg/L) but still could invade agar if methionine concentration is >40 mg/L. We will discuss possible mechanisms of methionine-induced morphogenesis in C. albicans.