Candida Albicans Binds Human Plasminogen: Identification of Eight Plasminogen-Binding Proteins

Mol Microbiol. 2003 Mar;47(6):1637-51. doi: 10.1046/j.1365-2958.2003.03390.x.

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 epsilon ACA, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminocaproic Acid / pharmacology
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Candida albicans / drug effects
  • Candida albicans / metabolism*
  • Cell Wall / metabolism
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Fibrinolysin / metabolism
  • Fluorescein-5-isothiocyanate / metabolism
  • Fluorescent Dyes / metabolism
  • Fungal Proteins / analysis*
  • Fungal Proteins / metabolism*
  • Humans
  • Mass Spectrometry / methods
  • Plasminogen / metabolism*
  • Plasminogen / pharmacology
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Tissue Plasminogen Activator / antagonists & inhibitors
  • Tissue Plasminogen Activator / pharmacology

Substances

  • Fluorescent Dyes
  • Fungal Proteins
  • Plasminogen
  • Tissue Plasminogen Activator
  • Fibrinolysin
  • Fluorescein-5-isothiocyanate
  • Aminocaproic Acid