UCSF

Qsp1 is a peptide of unknown function secreted by the fungal meningitis pathogen Cryptococcus neoformans. We identified QSP1 as a target of three transcription factors required for virulence. Indeed, mutants lacking Qsp1 are attenuated for infection and growth within macrophages. Qsp1 signaling modulates the activities of secreted proteases and promotes cell wall function at high cell densities. Production of the peptide requires its release from a secreted precursor by a cell- associated protease, while sensing of Qsp1 requires an oligopeptide importer. The effects of cytoplasmic expression of Qsp1 indicate that it can function intracellularly. These features closely mirror the quorum sensing systems of gram-positive bacteria in which peptide precursors are exported, processed and then imported to bind cytoplasmic receptors. Despite these remarkable similarities, the components of the respective systems are not ancestrally related, implying convergent evolution. Our studies reveal a bacterial-like signaling system that promotes the virulence of a eukaryotic pathogen.