The role of ammonium permeases in control of dimorphism and in pathogenicity of Candida albicans

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Under nitrogen starvation conditions the opportunistic fungal pathogen Candida albicans switches from the unicellular yeast form to a hyphal growth mode. This dimorphism, which is also regulated by other environmental signals, affects the expression of virulence-associated traits and is important for the capacity of C. albicans to cause infections. C. albicans possesses two ammonium permeases, CaMep1p and CaMep2p, that transport ammonium ions across the cytoplasmic membrane and allow growth when limiting concentrations of ammonium are the sole nitrogen source. In addition to being an ammonium transporter, CaMep2p, but not CaMep1p, is also essential for hyphal growth under nitrogen starvation conditions. The aim of this research project is to analyze how the expression and signaling activity of CaMep2p are regulated and to elucidate the mechanism of signal transduction by CaMep2p. To understand the CaMep2p-dependent response of C. albicans to nitrogen starvation on a genome-wide scale, the genes which are controlled by CaMep2p will be identified by transcription profiling. Finally, the importance of ammonium as a nitrogen source and of nitrogen starvation-induced hyphal growth for virulence in different host tissues in vivo will be investigated. These studies will provide insights into the relevance of nutrient regulation of morphogenesis for the pathogenicity of a major human fungal pathogen.