Chemical structure of Trichomonas vaginalis surface lipoglycan

a role for short galactose (beta 1-4/3) N-acetylglucosamine repeats in host cell interaction

Christopher M. Ryan, Angela Mehlert, Julia M. Richardson, Michael A. J. Ferguson, Patricia J. Johnson

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    The extracellular parasite Trichomonas vaginalis contains a surface glycoconjugate that appears to mediate parasite-host cell interaction via binding to human galectin-1. This glycoconjugate also elicits cytokine production from human vaginal epithelial cells, implicating its role in modulation of host immune responses. We have analyzed the structure of this glycoconjugate, previously described to contain the sugars rhamnose (Rha), N-acetylglucosamine (GlcNAc), galactose (Gal), xylose (Xyl), N-acetylgalactosamine (GalNAc), and glucose (Glc), using gas chromatograph mass spectrometry (GC-MS), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF), electrospray MS/MS, and nuclear magnetic resonance (NMR), combined with chemical and enzymatic digestions. Our data reveal a complex structure, named T. vaginalis lipoglycan (TvLG), that differs markedly from Leishmania lipophosphoglycan and Entamoeba lipopeptidophosphoglycan and is devoid of phosphosaccharide repeats. TvLG is composed of an alpha 1-3 linked polyrhamnose core, where Rha residues are substituted at the 2-position with either beta-Xyl or chains of, on average, five N-acetyllactosamine (-3Gal beta 1-4GlcNAc beta 1-) (LacNAc) units and occasionally lacto-N-biose (-3Gal beta 1-3GlcNAc beta 1-) (LNB). These chains are themselves periodically substituted at the Gal residues with Xyl-Rha. These structural analyses led us to test the role of the poly-LacNAc/LNB chains in parasite binding to host cells. We found that reduction of poly-LacNAc/LNB chains decreased the ability of TvLG to compete parasite binding to host cells. In summary, our data provide a new model for the structure of TvLG, composed of a polyrhamnose backbone with branches of Xyl and poly-LacNAc/LNB. Furthermore, the poly-LacNAc side chains are shown to be involved in parasite-host cell interaction.

    Original languageEnglish
    Pages (from-to)40494-40508
    Number of pages15
    JournalJournal of Biological Chemistry
    Volume286
    Issue number47
    DOIs
    Publication statusPublished - 25 Nov 2011

    Keywords

    • EPITHELIAL-CELLS
    • TRITRICHOMONAS-FETUS
    • LEISHMANIA-MAJOR
    • LIPOPHOSPHOGLYCAN
    • SACCHARIDES
    • PROTEINS
    • STRAINS
    • PATHOGENICITY
    • EUKARYOTES
    • EXPRESSION

    Cite this

    @article{2477cd47fc8e4fddb4dd3a43c8b31392,
    title = "Chemical structure of Trichomonas vaginalis surface lipoglycan: a role for short galactose (beta 1-4/3) N-acetylglucosamine repeats in host cell interaction",
    abstract = "The extracellular parasite Trichomonas vaginalis contains a surface glycoconjugate that appears to mediate parasite-host cell interaction via binding to human galectin-1. This glycoconjugate also elicits cytokine production from human vaginal epithelial cells, implicating its role in modulation of host immune responses. We have analyzed the structure of this glycoconjugate, previously described to contain the sugars rhamnose (Rha), N-acetylglucosamine (GlcNAc), galactose (Gal), xylose (Xyl), N-acetylgalactosamine (GalNAc), and glucose (Glc), using gas chromatograph mass spectrometry (GC-MS), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF), electrospray MS/MS, and nuclear magnetic resonance (NMR), combined with chemical and enzymatic digestions. Our data reveal a complex structure, named T. vaginalis lipoglycan (TvLG), that differs markedly from Leishmania lipophosphoglycan and Entamoeba lipopeptidophosphoglycan and is devoid of phosphosaccharide repeats. TvLG is composed of an alpha 1-3 linked polyrhamnose core, where Rha residues are substituted at the 2-position with either beta-Xyl or chains of, on average, five N-acetyllactosamine (-3Gal beta 1-4GlcNAc beta 1-) (LacNAc) units and occasionally lacto-N-biose (-3Gal beta 1-3GlcNAc beta 1-) (LNB). These chains are themselves periodically substituted at the Gal residues with Xyl-Rha. These structural analyses led us to test the role of the poly-LacNAc/LNB chains in parasite binding to host cells. We found that reduction of poly-LacNAc/LNB chains decreased the ability of TvLG to compete parasite binding to host cells. In summary, our data provide a new model for the structure of TvLG, composed of a polyrhamnose backbone with branches of Xyl and poly-LacNAc/LNB. Furthermore, the poly-LacNAc side chains are shown to be involved in parasite-host cell interaction.",
    keywords = "EPITHELIAL-CELLS, TRITRICHOMONAS-FETUS, LEISHMANIA-MAJOR, LIPOPHOSPHOGLYCAN, SACCHARIDES, PROTEINS, STRAINS, PATHOGENICITY, EUKARYOTES, EXPRESSION",
    author = "Ryan, {Christopher M.} and Angela Mehlert and Richardson, {Julia M.} and Ferguson, {Michael A. J.} and Johnson, {Patricia J.}",
    year = "2011",
    month = "11",
    day = "25",
    doi = "10.1074/jbc.M111.280578",
    language = "English",
    volume = "286",
    pages = "40494--40508",
    journal = "Journal of Biological Chemistry",
    issn = "0021-9258",
    publisher = "American Society for Biochemistry and Molecular Biology",
    number = "47",

    }

    Chemical structure of Trichomonas vaginalis surface lipoglycan : a role for short galactose (beta 1-4/3) N-acetylglucosamine repeats in host cell interaction. / Ryan, Christopher M.; Mehlert, Angela; Richardson, Julia M.; Ferguson, Michael A. J.; Johnson, Patricia J.

    In: Journal of Biological Chemistry, Vol. 286, No. 47, 25.11.2011, p. 40494-40508.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Chemical structure of Trichomonas vaginalis surface lipoglycan

    T2 - a role for short galactose (beta 1-4/3) N-acetylglucosamine repeats in host cell interaction

    AU - Ryan, Christopher M.

    AU - Mehlert, Angela

    AU - Richardson, Julia M.

    AU - Ferguson, Michael A. J.

    AU - Johnson, Patricia J.

    PY - 2011/11/25

    Y1 - 2011/11/25

    N2 - The extracellular parasite Trichomonas vaginalis contains a surface glycoconjugate that appears to mediate parasite-host cell interaction via binding to human galectin-1. This glycoconjugate also elicits cytokine production from human vaginal epithelial cells, implicating its role in modulation of host immune responses. We have analyzed the structure of this glycoconjugate, previously described to contain the sugars rhamnose (Rha), N-acetylglucosamine (GlcNAc), galactose (Gal), xylose (Xyl), N-acetylgalactosamine (GalNAc), and glucose (Glc), using gas chromatograph mass spectrometry (GC-MS), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF), electrospray MS/MS, and nuclear magnetic resonance (NMR), combined with chemical and enzymatic digestions. Our data reveal a complex structure, named T. vaginalis lipoglycan (TvLG), that differs markedly from Leishmania lipophosphoglycan and Entamoeba lipopeptidophosphoglycan and is devoid of phosphosaccharide repeats. TvLG is composed of an alpha 1-3 linked polyrhamnose core, where Rha residues are substituted at the 2-position with either beta-Xyl or chains of, on average, five N-acetyllactosamine (-3Gal beta 1-4GlcNAc beta 1-) (LacNAc) units and occasionally lacto-N-biose (-3Gal beta 1-3GlcNAc beta 1-) (LNB). These chains are themselves periodically substituted at the Gal residues with Xyl-Rha. These structural analyses led us to test the role of the poly-LacNAc/LNB chains in parasite binding to host cells. We found that reduction of poly-LacNAc/LNB chains decreased the ability of TvLG to compete parasite binding to host cells. In summary, our data provide a new model for the structure of TvLG, composed of a polyrhamnose backbone with branches of Xyl and poly-LacNAc/LNB. Furthermore, the poly-LacNAc side chains are shown to be involved in parasite-host cell interaction.

    AB - The extracellular parasite Trichomonas vaginalis contains a surface glycoconjugate that appears to mediate parasite-host cell interaction via binding to human galectin-1. This glycoconjugate also elicits cytokine production from human vaginal epithelial cells, implicating its role in modulation of host immune responses. We have analyzed the structure of this glycoconjugate, previously described to contain the sugars rhamnose (Rha), N-acetylglucosamine (GlcNAc), galactose (Gal), xylose (Xyl), N-acetylgalactosamine (GalNAc), and glucose (Glc), using gas chromatograph mass spectrometry (GC-MS), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF), electrospray MS/MS, and nuclear magnetic resonance (NMR), combined with chemical and enzymatic digestions. Our data reveal a complex structure, named T. vaginalis lipoglycan (TvLG), that differs markedly from Leishmania lipophosphoglycan and Entamoeba lipopeptidophosphoglycan and is devoid of phosphosaccharide repeats. TvLG is composed of an alpha 1-3 linked polyrhamnose core, where Rha residues are substituted at the 2-position with either beta-Xyl or chains of, on average, five N-acetyllactosamine (-3Gal beta 1-4GlcNAc beta 1-) (LacNAc) units and occasionally lacto-N-biose (-3Gal beta 1-3GlcNAc beta 1-) (LNB). These chains are themselves periodically substituted at the Gal residues with Xyl-Rha. These structural analyses led us to test the role of the poly-LacNAc/LNB chains in parasite binding to host cells. We found that reduction of poly-LacNAc/LNB chains decreased the ability of TvLG to compete parasite binding to host cells. In summary, our data provide a new model for the structure of TvLG, composed of a polyrhamnose backbone with branches of Xyl and poly-LacNAc/LNB. Furthermore, the poly-LacNAc side chains are shown to be involved in parasite-host cell interaction.

    KW - EPITHELIAL-CELLS

    KW - TRITRICHOMONAS-FETUS

    KW - LEISHMANIA-MAJOR

    KW - LIPOPHOSPHOGLYCAN

    KW - SACCHARIDES

    KW - PROTEINS

    KW - STRAINS

    KW - PATHOGENICITY

    KW - EUKARYOTES

    KW - EXPRESSION

    U2 - 10.1074/jbc.M111.280578

    DO - 10.1074/jbc.M111.280578

    M3 - Article

    VL - 286

    SP - 40494

    EP - 40508

    JO - Journal of Biological Chemistry

    JF - Journal of Biological Chemistry

    SN - 0021-9258

    IS - 47

    ER -