Author:

Keywords:

Candida albicans, morohogenesis

Abstract:

C. albicans is a human fungal pathogen. It lives commensally in most people and only causes infection when the immune system is compromised. The virulence of C. albicans depends on many different factors, but mostly on the yeast to hyphae transition. Not a specific morphology, but the capacity to switch between the different morphologies is crucial for virulence. Yeast cells are optimally placed to spread the infection, while hyphae can penetrate into the tissues and escape from macrophages. Many environmental cues like temperature, pH and specific amino acids affect this switch. One amino acid known to induce this switch is methionine. Its importance in virulence can be derived from the upregulation of nearly all methionine biosynthesis genes in certain infection associated conditions: upon internalization in macrophages and during biofilm formation. We investigate how methionine is sensed and how signalling is transduced in C. albicans. The GPCR Gpr1 and the high affinity methionine permease Mup1 were found to function in this process, as a deletion in either one of these genes causes a clear defect in methionine-induced morphogenesis. We proved that next to Gpr1 input, transport and metabolism of methionine are necessary for morphogenesis. This need for a dual input to activate the cAMP-PKA-pathway; GPCR-signalling and metabolism, is possibly similar to the mechanism for glucose in S. cerevisiae. Where both sensing and phosphorylation of glucose are needed to activate PKA.