Human gastric glycosphingolipids recognized by Helicobacter pylori vacuolating cytotoxin VacA |
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| Authors: | Roche Niamh Ilver Dag Angström Jonas Barone Silvia Telford John L Teneberg Susann |
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| Institution: | 1. Hubei Provincial Center for Disease Control and Prevention, Wuhan, The People''s Republic of China;4. Swiss Tropical and Public Health Institute, Basel, Switzerland;5. University of Basel, Basel, Switzerland;7. WHO Collaborating Centre for Tropical Diseases, Shanghai, The People''s Republic of China;8. Key Laboratory of Parasite and Vector Biology, MOH, Shanghai, The People''s Republic of China;1. GNS Science, Wairakei Research Centre, Private Bag 2000, Taupo 3330, New Zealand;2. Volcanic Risk Solutions, Institute of Agriculture and Environment, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand;1. Department of Bromatology, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland;2. Department of Food and Food Supplements, National Food and Nutrition Institute, Powsińska 61/63, 02-903 Warsaw, Poland |
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| Abstract: | Many bacterial toxins utilize cell surface glycoconjugate receptors for attachment to target cells. In the present study the potential carbohydrate binding of Helicobacter pylori vacuolating cytotoxin VacA was investigated by binding to human gastric glycosphingolipids on thin-layer chromatograms. Thereby a distinct binding of the toxin to two compounds in the non-acid glycosphingolipid fraction was detected. The VacA-binding glycosphingolipids were isolated and characterized by mass spectrometry and proton NMR as galactosylceramide (Galbeta1Cer) and galabiosylceramide (Galalpha4Galbeta1Cer). Comparison of the binding preferences of the protein to reference glycosphingolipids from other sources showed an additional recognition of glucosylceramide (Glcbeta1Cer), lactosylceramide (Galbeta4Glcbeta1Cer) and globotriaosylceramide (Galalpha4Galbeta4Glcbeta1Cer). No binding to the glycosphingolipids recognized by the VacA holotoxin was obtained with a mutant toxin with deletion of the 37 kDa fragment of VacA (P58 molecule). Collectively our data show that the VacA cytotoxin is a glycosphingolipid binding protein, where the 37 kDa moiety is required for carbohydrate recognition. The ability to bind to short chain glycosphingolipids will position the toxin close to the cell membrane, which may facilitate toxin internalization. |
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