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Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans
Author(s) -
Cox Gary M.,
McDade Henry C.,
Chen Sharon C. A.,
Tucker Stephanie C.,
Gottfredsson Magnus,
Wright Lesley C.,
Sorrell Tania C.,
Leidich Steven D.,
Casadevall Arturo,
Ghannoum Mahmoud A.,
Perfect John R.
Publication year - 2001
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2001.02236.x
Subject(s) - cryptococcus neoformans , biology , virulence , virulence factor , lysophospholipase , phospholipase , microbiology and biotechnology , extracellular , mutant , enzyme , phospholipase c , fungal protein , gene , biochemistry
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 .