Quorum-sensing-like peptide 1 (Qsp1) has been implicated as part of such a system in C. neoformans; QSP1 is predicted to encode a peptide precursor that contains a signal sequence and a pro-peptide (proQsp1). However, the specific role of Qsp1 remained unknown. Homer et al. now show that the expression of Qsp1 is regulated by key transcription factors that are involved in virulence (Gat201, Gat204 and Liv3), and that Qsp1 accumulates at high levels in cell culture supernatants. The authors also found that cells that lacked Qsp1 (qsp1Δ) were attenuated in a mouse inhalation model and that, in contrast to the wild-type, these mutants accumulated more slowly in primary macrophages. Together, these findings suggest that Qsp1 is a virulence factor in C. neoformans.
The authors also observed that qsp1Δ mutants formed dry colonies that were morphologically distinct from wild-type colonies. Interestingly, the addition of synthetic Qsp1 led to the formation of mutant colonies that resembled those that were formed by wild-type cells. The authors ruled out that the mutant colony phenotype was due to a lack of capsule, in fact they showed that mutants had enlarged capsules. Moreover, in saturated cultures, the authors observed that qsp1Δ cells are hypomelanized, and that this defect could partially be rescued through the addition of synthetic Qsp1. High-coverage RNA-sequencing revealed that, whereas wild-type or mutant cells that were grown in log-phase had similar gene expression profiles, numerous genes were differentially expressed in cells that were grown at saturating culture conditions. These findings suggest that the effect of Qsp1 is density dependent. Qsp1-regulated genes were enriched for genes that are involved in cell wall biogenesis and regulation. Indeed, mutant cells had thinner cell walls and lacked the distinct structural features of the cell wall that are found in wild-type cells. Together, these findings suggest that Qsp1 regulates growth and promotes cell wall function in a manner that is dependent on cell density.
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