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Cell Host Microbe DOI:10.1016/j.chom.2016.05.001

Intracellular Action of a Secreted Peptide Required for Fungal Virulence.

Publication TypeJournal Article
Year of Publication2016
AuthorsHomer, 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
JournalCell Host Microbe
Date Published2016 Jun 08

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.


Alternate JournalCell Host Microbe
PubMed ID27212659
PubMed Central IDPMC5186401
Grant ListP41 GM103533 / GM / NIGMS NIH HHS / United States
R01 AI073896 / AI / NIAID NIH HHS / United States
R21 AI122352 / AI / NIAID NIH HHS / United States
R01 AI096869 / AI / NIAID NIH HHS / United States
T32 GM008284 / GM / NIGMS NIH HHS / United States
T32 GM007618 / GM / NIGMS NIH HHS / United States
P41 RR011823 / RR / NCRR NIH HHS / United States
F30 HL120496 / HL / NHLBI NIH HHS / United States
R01 AI100272 / AI / NIAID NIH HHS / United States
R01 AG027463 / AG / NIA NIH HHS / United States
R01 AI080275 / AI / NIAID NIH HHS / United States