Intracellular Action of a Secreted Peptide Required for Fungal Virulence

Cell Host Microbe. 2016 Jun 8;19(6):849-64. doi: 10.1016/j.chom.2016.05.001. Epub 2016 May 19.


Quorum sensing (QS) is a bacterial communication mechanism in which secreted signaling molecules impact population function and gene expression. QS-like phenomena have been reported in eukaryotes with largely unknown contributing molecules, functions, and mechanisms. We identify Qsp1, a secreted peptide, as a central signaling molecule that regulates virulence in the fungal pathogen Cryptococcus neoformans. QSP1 is a direct target of three transcription factors required for virulence, and qsp1Δ mutants exhibit attenuated infection, slowed tissue accumulation, and greater control by primary macrophages. Qsp1 mediates autoregulatory signaling that modulates secreted protease activity and promotes cell wall function at high cell densities. Peptide production requires release from a secreted precursor, proQsp1, by a cell-associated protease, Pqp1. Qsp1 sensing requires an oligopeptide transporter, Opt1, and remarkably, cytoplasmic expression of mature Qsp1 complements multiple phenotypes of qsp1Δ. Thus, C. neoformans produces an autoregulatory peptide that matures extracellularly but functions intracellularly to regulate virulence.

MeSH terms

  • Animals
  • Cell Wall / physiology
  • Cryptococcosis / metabolism
  • Cryptococcosis / microbiology*
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / metabolism*
  • Cryptococcus neoformans / pathogenicity*
  • Disease Models, Animal
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Macrophages / metabolism
  • Melanins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Meningitis / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Peptide Hydrolases / metabolism
  • Quorum Sensing
  • Rabbits
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*


  • Fungal Proteins
  • Intercellular Signaling Peptides and Proteins
  • Melanins
  • Membrane Transport Proteins
  • Transcription Factors
  • Virulence Factors
  • peptide permease
  • Peptide Hydrolases