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

在氮饥饿条件下，机会性真菌病原体白色念珠菌从单细胞酵母形式转变为菌丝生长模式。这种二型性也受其他环境信号的调节，影响了毒力相关性状的表达，对C.白色念珠菌引起感染。C.白色念珠菌具有两种铵渗透酶，CaMep1p和CaMep2p，其运输铵离子穿过细胞质膜，并且当限制浓度的铵是唯一的氮源时允许生长。除了作为一个铵转运蛋白，CaMep2p，但不是CaMep1p，也是氮饥饿条件下菌丝生长所必需的。本研究的目的是分析CaMep2p的表达和信号活性是如何调节的，并阐明CaMep2p的信号转导机制。了解C.为了在全基因组范围内研究白念珠菌对氮饥饿的耐受性，将通过转录谱分析来鉴定受CaMep2p控制的基因。最后，铵作为氮源和氮饥饿诱导的菌丝生长在体内不同宿主组织中的毒力的重要性将进行研究。这些研究将提供深入了解营养调控的形态发生的致病性的主要人类真菌病原体的相关性。

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.