Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins.
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.
Crowe
Jonathan D
JD
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Sievwright
Isla K
IK
Auld
Gillian C
GC
Moore
Norma R
NR
Gow
Neil A R
NA
Booth
Nuala A
NA
D015119:Aminocaproic Acid / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005341:Fibrinolysin / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005656:Fungal Proteins / Q000032:analysis* / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010958:Plasminogen / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000494:pharmacology
D005456:Fluorescent Dyes; D005656:Fungal Proteins; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D016650:Fluorescein-5-isothiocyanate; D015119:Aminocaproic Acid