title: Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells.
abstract: Infection by the human opportunistic fungal pathogen Candida albicans has been increasing over recent years. In an attempt to understand the molecular mechanism of Candida invasion across host tissues, the relationship of C. albicans enolase to human plasminogen/plasmin was investigated. C. albicans enolase is a cell-surface protein and an immunodominant antigen in infected patients' sera. Plasminogen is an abundant plasma protein. Several lines of evidence support the binding of C. albicans enolase to human plasminogen. Firstly, it was found that various Candida strains were able to bind to plasminogen and its active form, plasmin. Secondly, recombinant Candida enolase was retained in a nickel-chelating affinity column matrix that can bind (125)I-labelled plasminogen or plasmin in a dose-dependent manner. Plasmin(ogen)-specific inhibitors, such as epsilon -aminocaproic acid and aprotinin, can effectively block plasmin-binding activity. Thirdly, as with many plasminogen receptors, binding of Candida enolase to plasmin(ogen) is lysine-dependent, whereas little inhibition occurred with arginine, aspartate and glutamate. Fourthly, immobilized enolase enhanced plasminogen's affinity for streptokinase at least tenfold, as demonstrated by its activation of plasmin activity. To elucidate the biological significance of this result, it was demonstrated that the plasmin(ogen)-bound Candida cells were able to induce fibrinolysis activity in a matrix-gel assay. Furthermore, plasmin-bound Candida cells had an increased ability to cross an in vitro blood-brain barrier system. The results given here indicate that Candida enolase is a plasminogen- and plasmin-binding protein and that the interaction of C. albicans enolase with the plasminogen system may contribute to invasion of the tissue barrier.
authors.affiliation: Division of Hematology-Oncology, Mailstop 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA 2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3,4Division of Infectious Diseases3 and Department of Surgery4, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Ambrose Y
authors.initials: AY
authors.lastname: Jong
authors.affiliation: Division of Hematology-Oncology, Mailstop 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA 2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3,4Division of Infectious Diseases3 and Department of Surgery4, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Steven H M
authors.initials: SHM
authors.lastname: Chen
authors.affiliation: Division of Hematology-Oncology, Mailstop 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA 2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3,4Division of Infectious Diseases3 and Department of Surgery4, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Monique F
authors.initials: MF
authors.lastname: Stins
authors.affiliation: Division of Hematology-Oncology, Mailstop 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA 2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3,4Division of Infectious Diseases3 and Department of Surgery4, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Mailstop 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA 2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3,4Division of Infectious Diseases3 and Department of Surgery4, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Tan-Lan
authors.initials: TL
authors.lastname: Tuan
authors.affiliation: Division of Hematology-Oncology, Mailstop 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA 2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3,4Division of Infectious Diseases3 and Department of Surgery4, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
mesh_terms: D001808:Blood Vessels / Q000166:cytology; D001921:Brain / Q000098:blood supply*; D002176:Candida albicans / Q000201:enzymology* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology*; D004800:Enzymes, Immobilized; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D005782:Gels / Q000378:metabolism; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000302:isolation & purification / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D013300:Streptokinase / Q000378:metabolism
chemical_list: D004800:Enzymes, Immobilized; D005782:Gels; D010958:Plasminogen; D013300:Streptokinase; D005341:Fibrinolysin; D010751:Phosphopyruvate Hydratase