The role of the transcription factor Stp2 in Candida albicans virulence

The fungal pathogen Candida albicans colonizes a variety of host niches, which confront the fungus with various environmental conditions, including different nutrients. To persist in the host C. albicans has developed a remarkable metabolic flexibility. Utilization of amino acids, an abundant host nutrient, is initiated by sensing and uptake via amino acid permeases. When amino acids serve as the sole carbon source, the fungal cell extrudes ammonium as a by-product of their metabolism in order to prevent cytotoxicity. This leads to alkalinisation of the environmental pH and triggering of hyphal morphogenesis, which, for example, contributes to fungal escape from the macrophage phagosomes.

The transcription factor Stp2 regulates the expression of general amino acids permeases and ammonium transporters, and is essential for growth on amino acids and pH modulation. Further, Stp2 has been connected to processes such as hyphal morphogenesis and heat shock response, suggesting a more global role in C. albicans virulence than expected. Therefore, in order to elucidate the role of Stp2, we have performed a transcriptional profiling of stp2∆ cells grown in amino acid-rich conditions and compared those to the wild-type strain SC5314. Our results confirm the role of Stp2 in regulation of amino acid metabolism and demonstrate a more global role for this transcription factor, as we observe differential regulation of genes involved in stress responses and hyphal growth. Since it remains elusive if the effect of Stp2 is direct or indirect, we plan to utilize ChIP-Sequencing to determine the genomic occupancy of Stp2 and to identify the exact binding motif. Altogether, our work should contribute to our understanding about the implications of metabolic adaptation to virulence.