Author:

Abstract:

The fungal pathogen Candida albicans can thrive in divergent microenvironments and change its cell morphology depending on the environmental conditions from budding yeast to hypha. This fungus appears to integrate numerous types of external signals to assess whether conditions are the most favourable for growth in particular cellular morphology. The ability of dimorphic pathogenic fungi to switch morphological states seems to be the important virulence determinant as mutant strains lacking this ability often have reduced virulence or are avirulent. Genes controlling morphogenesis have therefore been the focus of many investigations, as they have a great potential as target for antifungal drugs. Another fundamental aspect remains to be elucidated is how the yeast cells sense particular environmental factors. Studies of the switch from yeast to pseudohyphal growth in the model organism Saccharomyces cerevisiae revealed involvement of MAPK and cAMP-PKA cascades in this process, one of which is controlled by nutrient sensor Gpr1 – G-protein coupled receptor. In the yeast C. albicans was shown importance of analogous signalling cascades for the yeast morphogenesis. But despite of the extensive studies and growing number of the identified components involved in morphological switching, its actual mechanism, especially the early stages of sensing and signal transduction, is not fully understood. C. albicans contains a GPR1 homologue in its genome. We have shown that deletion of the CaGPR1 causes a strong defect of true mycelium formation during the growth on solid hypha-inducing media under different conditions. This defect could be suppressed by overexpression of TPK1, TPK2 but not EFG1, HST7 genes which role in yeast-to-hypha transition has been demonstrated. The presence of endogenous cAMP also rescues the wild type morphology during embedded growth at 37oC. Deletion of GPR1 has influenced neither growth rate and cell morphology in liquid media, nor susceptibility to antifungal agents and stress sensitivity. Interestingly that pathogenicity of gpr1Δ/gpr1Δ mutant during systemic infection in mouse model has been affected only slightly (20% survivors), but on the background of tps2Δ/tps2Δ mutation, which alone has resulted in 50% survivors, was fully blocked. We will consider the role of Gpr1p in the morphology differentiation in C. albicans.