Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans

Gary M. Cox, Henry C. McDade, Sharon C.A. Chen, Stephanie C. Tucker, Magnus Gottfredsson, Lesley C. Wright, Tania C. Sorrell, Steven D. Eidich, Arturo Casadevall, Mahmoud A. Ghannoum, John R. Perfect

Research output: Contribution to journalArticle

Abstract

The human pathogenic fungus Cryptococcus neoformans secretes a phospholipase enzyme that demonstrates phospholipase B (PLB), lysophospholipase hydrolase and lysophospholipase transacylase activities. This enzyme has been postulated to be a cryptococcal virulence factor. We cloned a phospholipase-encoding gene (PLB1) from C. neoformans and constructed plb1 mutants using targeted gene disruption. All three enzyme activities were markedly reduced in the mutants compared with the wild-type parent. The plb1 strains did not have any defects in the known cryptococcal virulence phenotypes of growth at 37°C, capsule formation, laccase activity and urease activity. The plb1 strains were reconstituted using the wild-type locus and this resulted in restoration of all extracellular PLB activities, in vivo testing demonstrated that the plb1 strain was significantly less virulent than the control strains in both the mouse inhalational model and the rabbit meningitis model. We also found that the plb1 strain exhibited a growth defect in a macrophage-like cell line. These data demonstrate that secretory phospholipase is a virulence factor for C. neoformans.

Original languageEnglish (US)
Pages (from-to)166-175
Number of pages10
JournalMolecular Microbiology
Volume39
Issue number1
DOIs
StatePublished - Jan 30 2001
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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  • Cite this

    Cox, G. M., McDade, H. C., Chen, S. C. A., Tucker, S. C., Gottfredsson, M., Wright, L. C., Sorrell, T. C., Eidich, S. D., Casadevall, A., Ghannoum, M. A., & Perfect, J. R. (2001). Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans. Molecular Microbiology, 39(1), 166-175. https://doi.org/10.1046/j.1365-2958.2001.02236.x