Candida albicans is the major fungal pathogen of humans. It is commonly found on the surfaces of oral and gastrointestinal mucosa in healthy individuals. However, in the immunocompromised patients, C. albicans is responsible for a number of severe systemic infections. One of the critical factors affecting microbial growth, persistence and virulence within the host is the ability of C. albicans to sense and respond to different environmental conditions, such as the nitrogen source. In a previous study, we found that a small GTPase Rhb1 functions as a positive regulator of the Tor1 kinase, which is the central component of the TOR (target of rapamycin) signaling pathway in response to ammonium availability. In this study, the main focus is to understand the role of Rhb1 and TOR in gene regulation for amino acid and protein assimilation. It is found that Rhb1 is involved in regulating the expression of amino acid permease gene GAP2 and secreted aspartyl protease gene SAP2, which is important for cell growth and virulence, respectively. Moreover, Rhb1-regulated Gap2 is specifically required for cell to utilize aromatic and some aliphatic amino acids as the nitrogen source. These processes of gene regulation for amino acid and protein assimilation were through the Tor1 kinase and its downstream transcriptional factors, Gat1, Stp1 and Stp2. Besides, the TOR signaling not only controls SAP2 but also affects expression of other members of the SAP family. Together, these results highlight the importance of Rhb1-TOR signaling pathway, nitrogen and their relevance to C. albicans virulence.

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