Editors' ChoiceQuorum Sensing

A quorum of fungi

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Science Signaling  14 Jun 2016:
Vol. 9, Issue 432, pp. ec137
DOI: 10.1126/scisignal.aag3255

Bacterial quorum-sensing systems control group behaviors, such as virulence, that depend on population density. Secreted quorum factors, which may be small molecules or peptides, stimulate group behaviors only after accumulating in the environment, ensuring that the bacteria do not waste energy on transcriptional and metabolic programs that are unlikely to benefit them. Homer et al. identified a quorum-sensing system that controls virulence in the pathogenic fungus Cryptococcus neoformans through the 11–amino acid peptide Qsp1 (quorum sensing–like peptide 1). After intranasal infection of mice, mutant C. neoformas lacking Qsp1 (qsp1Δ cells) showed decreased virulence and elicited an immune response distinct from that induced by wild-type (WT) C. neoformans. In culture, qsp1Δ cells formed dry, wrinkled colonies, whereas WT cells formed smooth, shiny colonies. Treating qsp1Δ cells with synthetic Qsp1 or placing them near WT cells converted the mutant colonies to the smooth phenotype. The abundance or activity of known virulence factors was altered in qsp1Δ cells compared with those in WT cells, and transcriptomic analysis indicated that many genes that were differentially expressed in qsp1Δ cells were involved in cell wall biosynthesis. At high cell density, qsp1Δ cells had thinner cell walls than WT cells and were more susceptible to stresses that compromise the cell wall. Qsp1 was produced extracellularly by proteolytic cleavage of the secreted 24–amino acid precursor proQsp1. A genetic screen identified Pqp1 as the secreted protease that processes proQsp1 and Opt1 as the oligopeptide transporter through which Qsp1 enters cells. An engineered form of Qsp1 that was produced intracellularly rescued the dry-colony and cell-wall phenotypes of the qsp1Δ cells, confirming that Qsp1 acted intracellularly. The receptor for Qsp1 has yet to be identified; however, the transcription factor Liv3 was required for most of the transcriptional responses to Qsp1, and liv3Δ mutants formed dry colonies. These results demonstrate that at least one species of fungus uses a quorum-sensing system to control virulence (see commentary by May).

C. M. Homer, D. K. Summers, A. I. Goranov, S. C. Clarke, D. L. Wiesner, J. K. Diedrich, J. J. Moresco, D. Toffaletti, R. Upadhya, I. Caradonna, S. Petnic, V. Pessino, C. A. Cuomo, J. K. Lodge, J. Perfect, J. R. Yates III, K. Nielsen, C. S. Craik,
H. D. Madhani, Intracellular action of a secreted peptide required for fungal virulence. Cell Host Microbe 19, 849–864 (2016). [PubMed]

R. C. May, Custom-made quorum sensing for a eukaryote. Dev. Cell 37, 391–392 (2016). [PubMed]

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