Dal81 Regulates Expression of Arginine Metabolism Genes in Candida parapsilosis

Abstract

Fungi can use a wide variety of nitrogen sources. In the absence of preferred sources such as ammonium, glutamate, and glutamine, secondary sources, including most other amino acids, are used. Expression of the nitrogen utilization pathways is very strongly controlled at the transcriptional level. Here, we investigated the regulation of nitrogen utilization in the pathogenic yeast <i>Candida parapsilosis</i>. We found that the functions of many regulators are conserved with respect to <i>Saccharomyces cerevisiae</i> and other fungi. For example, the core GATA activators <i>GAT1</i> and <i>GLN3</i> have a conserved role in nitrogen catabolite repression (NCR). There is one ortholog of <i>GZF3</i> and <i>DAL80</i>, which represses expression of genes in preferred nitrogen sources. The regulators <i>PUT3</i> and <i>UGA3</i> are required for metabolism of proline and γ-aminobutyric acid (GABA), respectively. However, the role of the Dal81 transcription factor is distinctly different. In <i>S. cerevisiae</i>, Dal81 is a positive regulator of acquisition of nitrogen from GABA, allantoin, urea, and leucine, and it is required for maximal induction of expression of the relevant pathway genes. In <i>C. parapsilosis</i>, induction of GABA genes is independent of Dal81, and deleting <i>DAL81</i> has no effect on acquisition of nitrogen from GABA or allantoin. Instead, Dal81 represses arginine synthesis during growth under preferred nitrogen conditions. <b>IMPORTANCE</b> Utilization of nitrogen by fungi is controlled by nitrogen catabolite repression (NCR). Expression of many genes is switched off during growth on nonpreferred nitrogen sources. Gene expression is regulated through a combination of activation and repression. Nitrogen regulation has been studied best in the model yeast <i>Saccharomyces cerevisiae</i>. We found that although many nitrogen regulators have a conserved function in <i>Saccharomyces</i> species, some do not. The Dal81 transcriptional regulator has distinctly different functions in <i>S. cerevisiae</i> and <i>C. parapsilosis</i>. In the former, it regulates utilization of nitrogen from GABA and allantoin, whereas in the latter, it regulates expression of arginine synthesis genes. Our findings make an important contribution to our understanding of nitrogen regulation in a human-pathogenic fungus.