Christina Homer (University of California, San Francisco)
Infection by many bacteria requires coordination through secreted signaling molecules, but whether this is true for fungal pathogens remains unknown. Using the pathogenic fungus Cryptococcus neoformans, we defined the first peptide-based quorum-sensing system that promotes virulence in a eukaryotic pathogen. QSP1 is a gene encoding a secreted peptide that accumulates as cell density increases. Strikingly, mouse infections reveal that C. neoformans lacking the QSP1 gene have attenuated virulence. Qsp1 signaling modulates multiple cellular functions. Production of the peptide requires its release from a secreted precursor by a cell-associated protease, while sensing of Qsp1 requires an oligopeptide importer. These features closely mirror the quorum sensing signaling systems of certain bacteria in which peptide precursors are exported, processed and then imported to bind cytoplasmic receptors. Despite these remarkable similarities, these systems are not ancestrally related, implying convergent evolution and selection for these types of signaling systems.