SRA

Candida albicans is a member of the normal commensal flora with the ability to cause disease in susceptible individuals. Nutrient acquisition is of central importance for C. albicans to colonize and thrive in the host. We have previously assessed the role of amino acid utilization for growth and manipulation of pH, triggering the filamentation program and promoting immune evasion. While the role of amino acids has been largely studied, protein utilization has remained less well understood. We investigated the utilization of peptides as a source of carbon and to support the neutralization phenomena. We found that both transcription factors Stp1 and Stp2 are required for proper peptide utilization in a manner dependent of amino acid sensing signaling involving the SPS system. However, we found that Stp2 is the major contributor for this process. Epistasis experiments shown that Stp1 partially restores the ability to utilize peptides in the absence of amino acid signaling, whilst Stp2 is sufficient to fully restore this phenotype. Transcriptomic analysis revealed that the response to amino acids and peptides is very similar, but peptides represent a more difficult carbon source to utilize. It is known that the Stp1/Stp2 duet has divergent roles in C. albicans, however the specific set of genes controlled by each TF remained unclear. We showed that the Stp1 regulon is limited to two oligopeptide transporters (OPT1, OPT9), and iron-acquisition oxidoreductase (CFL2), a nucleoside transporter (NUP) and a leucine aminopeptidase (APE2), whereas Stp2 is responsible for the regulation of amino acid uptake and catabolic genes, in a manner dependent of amino acid sensing. Surprisingly, Stp2 affects expression of genes involved in the filamentation response (e.g. UME6, SFL2) that have been associated with host colonization. In a GI tract competition experiment, mutants lacking the amino acid sensor Ssy1 or the TF Stp2 exhibited decreased colonization, while an stp1?/? mutant showed increase colonization. Taken together, these results highlight the importance of peptide and amino acid utilization for colonization of the host, a prerequisite for disseminated disease. Overall design: Examination of wild-type and mutant C. albicans transcriptomes under different carbon source conditions.