Coordinate genomic association of transcription factors controlled by an imported quorum sensing peptide in Cryptococcus neoformans
Qsp1 is secreted quorum sensing peptide required for virulence of the fungal meningitis pathogen Cryptococcus neoformans. Qsp1 functions to control cell wall integrity in vegetatively growing cells and also functions in mating. We found that rather than acting on a cell surface receptor, Qsp1 is imported to act intracellularly via the predicted oligopeptide transporter Opt1. We also demonstrate that a transcription factor network is a target of Qsp1. Qsp1 controls the genomic associations of three transcription factors to genes whose outputs are regulated by Qsp1. One of these transcription factors, Cqs2, is also required for Qsp1’s action in mating, indicating that it might be a shared proximal target of Qsp1. Consistent with this hypothesis deletion of CQS2 impacts the binding of other network transcription factors specifically to Qsp1-regulated genes. These genetic and genomic studies illuminate mechanisms by which an imported peptide acts to modulate eukaryotic gene expression.