Helicobacter pylori is a bacterium that colonizes the stomach of a majority of the global human population causing common gastric diseases like ulcers and cancer. It has an unusually complex pattern of binding to various host glycoconjugates including interaction with sialylated, sulfated, and fucosylated sequences. The present study describes an additional binding epitope comprising the neolacto internal sequence of GlcNAcβ3-Galβ4GlcNAcβ. The binding was detected on TLC plates as an interaction with a seven-sugar ganglioside of rabbit thymus. The glycolipid was purified and characterized as Neu5Gcα3Galβ4GlcNAcβ3Galβ4GlcNAcβ3-Galβ4Glcβ1Cer with less than 10% of the fraction carrying a repeated lacto (type-1) core chain, Galβ3Glc-NAcβ3Galβ3GlcNAcβ. After stepwise chemical and enzymatic degradation and structural analysis of products the strongest binder was found to be the pentaglycosylceramide GlcNAcβ3Galβ4GlcNAcβ3Galβ4Glcβ1-Cer, whereas the hexa- and tetraglycosylceramides were less active, and the trihexosylceramide was inactive. Further studies revealed that the terminal GlcNAcβ of the pentaglycosylceramide may be exchanged for either GalNAcβ3, GalNAcα3, or Galα3 without loss of the activity. Calculated minimum energy conformers of these four isoreceptors show a substantial topographical similarity suggesting that this binding is a result of a molecular mimicry. Although the glycoconjugate composition of human gastric epithelial cells is not known in detail it is proposed that repeating N-acetyllactosamine units of glycoconjugates may serve as bacterial attachment sites in the stomach.
This work was supported by Swedish Research Council Grant 06X-12628, the Swedish Cancer Foundation, Wilhelm and Martina Lundgrens Research Foundation, the Swedish Medical Society, the Adlerbertska Research Foundation, Ingabritt and Arne Lundberg Foundation, and Symbicom Ltd. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
