Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins

Jonathan David Crowe, I. K. Sievwright, G. C. Auld, Norma Ross Moore, Neil Andrew Robert Gow, Nuala Ann Booth

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Several microbial pathogens augment their invasive potential by binding and activating human plasminogen to generate the proteolytic enzyme plasmin. Yeast cells and cell wall proteins (CWP) of the human pathogenic fungus Candida albicans bound plasminogen with a K-d of 70 +/- 11 nM and 112 +/- 20 nM respectively. Bound plasminogen could be activated to plasmin by mammalian plasminogen activators; no C. albicans plasminogen activator was detected. Binding of plasminogen to CWP and whole cells was inhibited by epsilonACA, indicating that binding was predominantly to lysine residues. Candida albicans mutant strains defective in protein glycosylation did not show altered plasminogen binding, suggesting that binding was not mediated via a surface lectin. Binding was sensitive to digestion by basic carboxypeptidase, implicating C-terminal lysine residues in binding. Proteomic analysis identified eight major plasminogen-binding proteins in isolated CWP. Five of these (phosphoglycerate mutase, alcohol dehydrogenase, thioredoxin peroxidase, catalase, transcription elongation factor) had C-terminal lysine residues and three (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and fructose bisphosphate aldolase) did not. Activation of plasminogen could potentially increase the capacity of this pathogenic fungus for tissue invasion and necrosis. Although surface-bound plasmin(ogen) degraded fibrin, no direct evidence for a role in invasion of endothelial matrix or in penetration and damage of endothelial cells was found.

Original languageEnglish
Pages (from-to)1637-1651
Number of pages14
JournalMolecular Microbiology
Volume47
Issue number6
DOIs
Publication statusPublished - Mar 2003

Keywords

  • EXTRACELLULAR-MATRIX PROTEINS
  • SECRETED ASPARTYL PROTEINASES
  • CELL-WALL PROTEINS
  • ACTIVATOR T-PA
  • SACCHAROMYCES-CEREVISIAE
  • GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
  • STREPTOCOCCUS-PNEUMONIAE
  • POLYACRYLAMIDE GELS
  • ENDOTHELIAL-CELLS
  • MASS-SPECTROMETRY

Cite this

Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. / Crowe, Jonathan David; Sievwright, I. K.; Auld, G. C.; Moore, Norma Ross; Gow, Neil Andrew Robert; Booth, Nuala Ann.

In: Molecular Microbiology, Vol. 47, No. 6, 03.2003, p. 1637-1651.

Research output: Contribution to journalArticle

Crowe, Jonathan David ; Sievwright, I. K. ; Auld, G. C. ; Moore, Norma Ross ; Gow, Neil Andrew Robert ; Booth, Nuala Ann. / Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. In: Molecular Microbiology. 2003 ; Vol. 47, No. 6. pp. 1637-1651.
@article{1ee9aa58888a4617a570f8ce33c4bfcf,
title = "Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins",
abstract = "Several microbial pathogens augment their invasive potential by binding and activating human plasminogen to generate the proteolytic enzyme plasmin. Yeast cells and cell wall proteins (CWP) of the human pathogenic fungus Candida albicans bound plasminogen with a K-d of 70 +/- 11 nM and 112 +/- 20 nM respectively. Bound plasminogen could be activated to plasmin by mammalian plasminogen activators; no C. albicans plasminogen activator was detected. Binding of plasminogen to CWP and whole cells was inhibited by epsilonACA, indicating that binding was predominantly to lysine residues. Candida albicans mutant strains defective in protein glycosylation did not show altered plasminogen binding, suggesting that binding was not mediated via a surface lectin. Binding was sensitive to digestion by basic carboxypeptidase, implicating C-terminal lysine residues in binding. Proteomic analysis identified eight major plasminogen-binding proteins in isolated CWP. Five of these (phosphoglycerate mutase, alcohol dehydrogenase, thioredoxin peroxidase, catalase, transcription elongation factor) had C-terminal lysine residues and three (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and fructose bisphosphate aldolase) did not. Activation of plasminogen could potentially increase the capacity of this pathogenic fungus for tissue invasion and necrosis. Although surface-bound plasmin(ogen) degraded fibrin, no direct evidence for a role in invasion of endothelial matrix or in penetration and damage of endothelial cells was found.",
keywords = "EXTRACELLULAR-MATRIX PROTEINS, SECRETED ASPARTYL PROTEINASES, CELL-WALL PROTEINS, ACTIVATOR T-PA, SACCHAROMYCES-CEREVISIAE, GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, STREPTOCOCCUS-PNEUMONIAE, POLYACRYLAMIDE GELS, ENDOTHELIAL-CELLS, MASS-SPECTROMETRY",
author = "Crowe, {Jonathan David} and Sievwright, {I. K.} and Auld, {G. C.} and Moore, {Norma Ross} and Gow, {Neil Andrew Robert} and Booth, {Nuala Ann}",
year = "2003",
month = "3",
doi = "10.1046/j.1365-2958.2003.03390.x",
language = "English",
volume = "47",
pages = "1637--1651",
journal = "Molecular Microbiology",
issn = "0950-382X",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins

AU - Crowe, Jonathan David

AU - Sievwright, I. K.

AU - Auld, G. C.

AU - Moore, Norma Ross

AU - Gow, Neil Andrew Robert

AU - Booth, Nuala Ann

PY - 2003/3

Y1 - 2003/3

N2 - Several microbial pathogens augment their invasive potential by binding and activating human plasminogen to generate the proteolytic enzyme plasmin. Yeast cells and cell wall proteins (CWP) of the human pathogenic fungus Candida albicans bound plasminogen with a K-d of 70 +/- 11 nM and 112 +/- 20 nM respectively. Bound plasminogen could be activated to plasmin by mammalian plasminogen activators; no C. albicans plasminogen activator was detected. Binding of plasminogen to CWP and whole cells was inhibited by epsilonACA, indicating that binding was predominantly to lysine residues. Candida albicans mutant strains defective in protein glycosylation did not show altered plasminogen binding, suggesting that binding was not mediated via a surface lectin. Binding was sensitive to digestion by basic carboxypeptidase, implicating C-terminal lysine residues in binding. Proteomic analysis identified eight major plasminogen-binding proteins in isolated CWP. Five of these (phosphoglycerate mutase, alcohol dehydrogenase, thioredoxin peroxidase, catalase, transcription elongation factor) had C-terminal lysine residues and three (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and fructose bisphosphate aldolase) did not. Activation of plasminogen could potentially increase the capacity of this pathogenic fungus for tissue invasion and necrosis. Although surface-bound plasmin(ogen) degraded fibrin, no direct evidence for a role in invasion of endothelial matrix or in penetration and damage of endothelial cells was found.

AB - Several microbial pathogens augment their invasive potential by binding and activating human plasminogen to generate the proteolytic enzyme plasmin. Yeast cells and cell wall proteins (CWP) of the human pathogenic fungus Candida albicans bound plasminogen with a K-d of 70 +/- 11 nM and 112 +/- 20 nM respectively. Bound plasminogen could be activated to plasmin by mammalian plasminogen activators; no C. albicans plasminogen activator was detected. Binding of plasminogen to CWP and whole cells was inhibited by epsilonACA, indicating that binding was predominantly to lysine residues. Candida albicans mutant strains defective in protein glycosylation did not show altered plasminogen binding, suggesting that binding was not mediated via a surface lectin. Binding was sensitive to digestion by basic carboxypeptidase, implicating C-terminal lysine residues in binding. Proteomic analysis identified eight major plasminogen-binding proteins in isolated CWP. Five of these (phosphoglycerate mutase, alcohol dehydrogenase, thioredoxin peroxidase, catalase, transcription elongation factor) had C-terminal lysine residues and three (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and fructose bisphosphate aldolase) did not. Activation of plasminogen could potentially increase the capacity of this pathogenic fungus for tissue invasion and necrosis. Although surface-bound plasmin(ogen) degraded fibrin, no direct evidence for a role in invasion of endothelial matrix or in penetration and damage of endothelial cells was found.

KW - EXTRACELLULAR-MATRIX PROTEINS

KW - SECRETED ASPARTYL PROTEINASES

KW - CELL-WALL PROTEINS

KW - ACTIVATOR T-PA

KW - SACCHAROMYCES-CEREVISIAE

KW - GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE

KW - STREPTOCOCCUS-PNEUMONIAE

KW - POLYACRYLAMIDE GELS

KW - ENDOTHELIAL-CELLS

KW - MASS-SPECTROMETRY

U2 - 10.1046/j.1365-2958.2003.03390.x

DO - 10.1046/j.1365-2958.2003.03390.x

M3 - Article

VL - 47

SP - 1637

EP - 1651

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 6

ER -