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Intracellular Action of a Secreted Peptide Required for Fungal Virulence.

Publication ,  Journal Article
Homer, CM; Summers, DK; Goranov, AI; Clarke, SC; Wiesner, DL; Diedrich, JK; Moresco, JJ; Toffaletti, D; Upadhya, R; Caradonna, I; Petnic, S ...
Published in: Cell Host Microbe
June 8, 2016

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.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

June 8, 2016

Volume

19

Issue

6

Start / End Page

849 / 864

Location

United States

Related Subject Headings

  • Virulence Factors
  • Transcription Factors
  • Rabbits
  • Quorum Sensing
  • Peptide Hydrolases
  • Mutation
  • Mice, Inbred C57BL
  • Mice
  • Meningitis
  • Membrane Transport Proteins
 

Citation

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Homer, C. M., Summers, D. K., Goranov, A. I., Clarke, S. C., Wiesner, D. L., Diedrich, J. K., … Madhani, H. D. (2016). Intracellular Action of a Secreted Peptide Required for Fungal Virulence. Cell Host Microbe, 19(6), 849–864. https://doi.org/10.1016/j.chom.2016.05.001
Homer, Christina M., Diana K. Summers, Alexi I. Goranov, Starlynn C. Clarke, Darin L. Wiesner, Jolene K. Diedrich, James J. Moresco, et al. “Intracellular Action of a Secreted Peptide Required for Fungal Virulence.Cell Host Microbe 19, no. 6 (June 8, 2016): 849–64. https://doi.org/10.1016/j.chom.2016.05.001.
Homer CM, Summers DK, Goranov AI, Clarke SC, Wiesner DL, Diedrich JK, et al. Intracellular Action of a Secreted Peptide Required for Fungal Virulence. Cell Host Microbe. 2016 Jun 8;19(6):849–64.
Homer, Christina M., et al. “Intracellular Action of a Secreted Peptide Required for Fungal Virulence.Cell Host Microbe, vol. 19, no. 6, June 2016, pp. 849–64. Pubmed, doi:10.1016/j.chom.2016.05.001.
Homer CM, Summers DK, Goranov AI, Clarke SC, Wiesner DL, Diedrich JK, Moresco JJ, Toffaletti D, Upadhya R, Caradonna I, Petnic S, Pessino V, Cuomo CA, Lodge JK, Perfect J, Yates JR, Nielsen K, Craik CS, Madhani HD. Intracellular Action of a Secreted Peptide Required for Fungal Virulence. Cell Host Microbe. 2016 Jun 8;19(6):849–864.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

June 8, 2016

Volume

19

Issue

6

Start / End Page

849 / 864

Location

United States

Related Subject Headings

  • Virulence Factors
  • Transcription Factors
  • Rabbits
  • Quorum Sensing
  • Peptide Hydrolases
  • Mutation
  • Mice, Inbred C57BL
  • Mice
  • Meningitis
  • Membrane Transport Proteins