Phospholipase Activity in Cryptococcus neoformans: A New Virulence Factor?

Chen, Wen; Müller, Michael; Zhou, Jin Zhong; Wright, Lesley C.; Sorrell, Tania C.

doi:10.1093/infdis/175.2.414

Cited by 155 publications

(125 citation statements)

References 20 publications

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“…No other phospholipase or lipase activities were identified. Analysis of four cryptococcal strains with various levels of phospholipase activity revealed a correlation between phospholipase activity and virulence in BALB\c mice [22]. We also showed that phospholipid components of lung surfactant and cellular membranes were targets for C. neoformans phospholipases in their natural state [24].…”

Section: Introductionmentioning

confidence: 67%

“…neoformans, BL-1, from the culture collection at Westmead Hospital was studied. Extracellular phospholipase production by this isolate has been previously identified [22,23]. Working cultures were stored at 4 mC on SDA.…”

Section: Organism and Enzyme Preparationmentioning

confidence: 99%

“…Enzyme activities were measured as described previously [22,23] in a final volume of 0.25 ml, using 1-2 µg of total protein, at 37 mC. For the determination of PLB activity, carrier DPPC (final concentration 400 µM) and 1,2-di[1-"%C]palmitoyl PC (20 000 d.p.m.)…”

Section: Radiometric Assaymentioning

confidence: 99%

“…We previously reported extracellular phospholipase production in a large number of C. neoformans isolates and identified the enzyme activities in one clinical isolate (strain BL-1) as LPL, LPTA and PLB by applying radiometric analysis using TLC and NMR spectroscopy [22,23]. No other phospholipase or lipase activities were identified.…”

Section: Introductionmentioning

confidence: 99%

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Purification and characterization of secretory phospholipase B, lysophospholipase and lysophospholipase/transacylase from a virulent strain of the pathogenic fungus Cryptococcus neoformans

Chen

Wright

GOLDING³

et al. 2000

Biochemical Journal

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Infection caused by the fungus Cryptococcus neoformans is potentially fatal. A highly active extracellular phospholipase, demonstrating phospholipase B (PLB), lysophospholipase (LPL) and lysophospholipase\transacylase (LPTA) activities, was purified to homogeneity from C. neoformans using (NH % ) # SO % fractionation, and hydrophobic-interaction, anion-exchange and gel-filtration chromatography. All three enzyme activities copurified as a single protein with an apparent molecular mass of 70-90 kDa by SDS\PAGE and 160-180 kDa by gel filtration. The ratio of the three activities remained constant after each purification step. The amino acid composition, as well as the sequences of the N-terminus and of five internal peptide fragments were novel. The protein was an acidic glycoprotein containing Nlinked carbohydrate moieties, with pI values of 5.5 and 3.5. The apparent V max values for PLB and LPL activities were 12.3 and 870 µmol\min per mg of protein respectively ; the corresponding

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Section: Introductionmentioning

confidence: 67%

Section: Organism and Enzyme Preparationmentioning

confidence: 99%

Section: Radiometric Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Purification and characterization of secretory phospholipase B, lysophospholipase and lysophospholipase/transacylase from a virulent strain of the pathogenic fungus Cryptococcus neoformans

Chen

Wright

GOLDING³

et al. 2000

Biochemical Journal

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“…The secreted enzyme, phospholipase B (Plb1), 2 is an established cryptococcal virulence determinant (1). It facilitates invasion of host lung tissue (2), most likely by hydrolyzing phospholipids in mammalian cell membranes and pulmonary surfactant (3)(4)(5)(6) and is essential for hematogenous dissemination of infection (2). In the cryptococcal cell, Plb1 is localized in specialized membrane domains known as rafts (7).…”

mentioning

confidence: 99%

Cell Wall-linked Cryptococcal Phospholipase B1 Is a Source of Secreted Enzyme and a Determinant of Cell Wall Integrity

Siafakas

Sorrell

Wright

et al. 2007

Journal of Biological Chemistry

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Phospholipase B (Plb1) is secreted by pathogenic fungi and is a proven virulence determinant in Cryptococcus neoformans. Cell-associated Plb1 is presumptively involved in fungal membrane biogenesis and remodelling. We have also identified it in cryptococcal cell walls. Motif scanning programs predict that Plb1 is attached to cryptococcal membranes via a glycosylphosphatidylinositol (GPI) anchor, which could regulate Plb1 export and secretion. A functional GPI anchor was identified in cellassociated Plb1 by (G)PI-specific phospholipase C (PLC)-induced release of Plb1 from strain H99 membrane rafts and inhibition of GPI anchor synthesis by YW3548, which prevented Plb1 secretion and transport to membranes and cell walls. Plb1 containing ␤-1,6-linked glucan was released from H99 (wildtype strain) cell walls by ␤-1,3 glucanase, consistent with covalent attachment of Plb1 via ␤-1,6-linked glucans to ␤-1,3-linked glucan in the central scaffold of the wall. Naturally secreted Plb1 also contained ␤-1,6-linked glucan, confirming that it originated from the cell wall. Plb1 maintains cell wall integrity because a H99 deletion mutant, ⌬PLB1, exhibited a morphological defect and was more susceptible than H99 to cell wall disruption by SDS and Congo red. Growth of ⌬PLB1 was unaffected by caffeine, excluding an effect of Plb1 on cell wall biogenesis-related signaling pathways. Environmental (heat) stress caused Plb1 accumulation in cell walls, with loss from membranes and reduced secretion, further supporting the importance of Plb1 in cell wall integrity. This is the first demonstration that Plb1 contributes to fungal survival by maintaining cell wall integrity and that the cell wall is a source of secreted enzyme.

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Heteronuclear NMR studies of metabolites produced byCryptococcus neoformans in culture media: Identification of possible virulence factors

et al. 1999

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Phospholipase Activity in Cryptococcus neoformans: A New Virulence Factor?

Cited by 155 publications

References 20 publications

Purification and characterization of secretory phospholipase B, lysophospholipase and lysophospholipase/transacylase from a virulent strain of the pathogenic fungus Cryptococcus neoformans

Purification and characterization of secretory phospholipase B, lysophospholipase and lysophospholipase/transacylase from a virulent strain of the pathogenic fungus Cryptococcus neoformans

Cell Wall-linked Cryptococcal Phospholipase B1 Is a Source of Secreted Enzyme and a Determinant of Cell Wall Integrity

Heteronuclear NMR studies of metabolites produced byCryptococcus neoformans in culture media: Identification of possible virulence factors

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