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

Intracellular Action of a Secreted Peptide Required for Fungal Virulence.

Author information

1
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
4
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
5
Department of Medicine, Duke University, Durham, NC 27710, USA.
6
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
8
Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
9
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: hitenmadhani@gmail.com.

Abstract

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.

PMID:
27212659
PMCID:
PMC5186401
DOI:
10.1016/j.chom.2016.05.001
[Indexed for MEDLINE]
Free PMC Article

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