Projects per year
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 language | English |
---|---|
Pages (from-to) | 40494-40508 |
Number of pages | 15 |
Journal | Journal of Biological Chemistry |
Volume | 286 |
Issue number | 47 |
DOIs | |
Publication status | Published - 25 Nov 2011 |
Keywords
- EPITHELIAL-CELLS
- TRITRICHOMONAS-FETUS
- LEISHMANIA-MAJOR
- LIPOPHOSPHOGLYCAN
- SACCHARIDES
- PROTEINS
- STRAINS
- PATHOGENICITY
- EUKARYOTES
- EXPRESSION
Fingerprint
Dive into the research topics of 'Chemical structure of Trichomonas vaginalis surface lipoglycan: a role for short galactose (beta 1-4/3) N-acetylglucosamine repeats in host cell interaction'. Together they form a unique fingerprint.Projects
- 2 Finished
-
Aref#d: 20731. The Biosynthesis of Glycoproteins in Trypanosoma Brucei: Basic and Translational Research
1/10/08 → 31/05/14
Project: Research
-
Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)
Fairlamb, A., Ferguson, M. & Frearson, J.
1/01/08 → 31/12/12
Project: Research