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Candida albicans binds human plasminogen: identification of eight plasminogen‐binding proteins
Author(s) -
Crowe Jonathan D.,
Sievwright Isla K.,
Auld Gillian C.,
Moore Norma R.,
Gow Neil A. R.,
Booth Nuala A.
Publication year - 2003
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.1365-2958.2003.03390.x
Subject(s) - plasmin , biology , biochemistry , candida albicans , phosphoglycerate mutase , plasminogen activator , microbiology and biotechnology , carboxypeptidase , binding site , enzyme , glycolysis , endocrinology
Summary 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 ɛACA, 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.