HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jong, A. Y. Articles by Huang, S.-H. Search for Related Content PubMed PubMed Citation Articles by Jong, A. Y. Articles by Huang, S.-H. Agricola Articles by Jong, A. Y. Articles by Huang, S.-H.

Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells

Ambrose Y. Jong^1, , Steven H. M. Chen^1, , Monique F. Stins², Kwang Sik Kim², Tan-Lan Tuan³ and Sheng-He Huang⁴

¹Division 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

Correspondence Ambrose Y. Jong ajong{at}chla.usc.edu

Received August 28, 2002
Accepted December 6, 2002

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 ¹²⁵I-labelled plasminogen or plasmin in a dose-dependent manner. Plasmin(ogen)-specific inhibitors, such as -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.

Abbreviations: EACA, -aminocaproic acid; ECM, extracellular matrix; HBMEC, human brain microvascular endothelial cells; Ni-NTA, nickel nitrilotriacetic acid; SAP, secreted aspartyl proteinase; TEER, transendothelial electric resistance; tPA, tissue-type plasminogen activator.

This article has been cited by other articles:

				A. Lama, A. Kucknoor, V. Mundodi, and J. F. Alderete Glyceraldehyde-3-Phosphate Dehydrogenase Is a Surface-Associated, Fibronectin-Binding Protein of Trichomonas vaginalis Infect. Immun., July 1, 2009; 77(7): 2703 - 2711. [Abstract] [Full Text] [PDF]

				W. L. Chaffin Candida albicans Cell Wall Proteins Microbiol. Mol. Biol. Rev., September 1, 2008; 72(3): 495 - 544. [Abstract] [Full Text] [PDF]

				M. Esgleas, Y. Li, M. A. Hancock, J. Harel, J. D. Dubreuil, and M. Gottschalk Isolation and characterization of {alpha}-enolase, a novel fibronectin-binding protein from Streptococcus suis Microbiology, September 1, 2008; 154(9): 2668 - 2679. [Abstract] [Full Text] [PDF]

				C. Gancedo and C.-L. Flores Moonlighting Proteins in Yeasts Microbiol. Mol. Biol. Rev., March 1, 2008; 72(1): 197 - 210. [Abstract] [Full Text] [PDF]

				V. Mundodi, A. S. Kucknoor, and J. F. Alderete Immunogenic and Plasminogen-Binding Surface-Associated {alpha}-Enolase of Trichomonas vaginalis Infect. Immun., February 1, 2008; 76(2): 523 - 531. [Abstract] [Full Text] [PDF]

				A. Kunert, J. Losse, C. Gruszin, M. Huhn, K. Kaendler, S. Mikkat, D. Volke, R. Hoffmann, T. S. Jokiranta, H. Seeberger, et al. Immune Evasion of the Human Pathogen Pseudomonas aeruginosa: Elongation Factor Tuf Is a Factor H and Plasminogen Binding Protein J. Immunol., September 1, 2007; 179(5): 2979 - 2988. [Abstract] [Full Text] [PDF]

				J. Kolberg, A. Aase, S. Bergmann, T. K. Herstad, G. Rodal, R. Frank, M. Rohde, and S. Hammerschmidt Streptococcus pneumoniae enolase is important for plasminogen binding despite low abundance of enolase protein on the bacterial cell surface. Microbiology, May 1, 2006; 152(Pt 5): 1307 - 1317. [Abstract] [Full Text] [PDF]

				A. Pitarch, A. Jimenez, C. Nombela, and C. Gil Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses Mol. Cell. Proteomics, January 1, 2006; 5(1): 79 - 96. [Abstract] [Full Text] [PDF]