<i>Helicobacter suis</i> binding to carbohydrates on human and porcine gastric mucins and glycolipids occurs via two modes

<i>Helicobacter suis</i> colonizes the stomach of most pigs and is the most prevalent non-<i>Helicobacter pylori</i> Helicobacter species found in the human stomach. In the human host, <i>H. suis</i> contributes to the development of chronic gastritis, peptic ulcer disease and MALT lymphoma, whereas in pigs it is associated with gastritis, decreased growth and ulcers. Here, we demonstrate that the level of <i>H. pylori</i> and <i>H. suis</i> binding to human and pig gastric mucins varies between individuals with species dependent specificity. The binding optimum of <i>H. pylori</i> is at neutral pH whereas that of <i>H. suis</i> has an acidic pH optimum, and the mucins that <i>H. pylori</i> bind to are different than those that <i>H. suis</i> bind to. Mass spectrometric analysis of mucin <i>O</i>-glycans from the porcine mucin showed that individual variation in binding is reflected by a difference in glycosylation; of 109 oligosaccharide structures identified, only 14 were present in all examined samples. <i>H. suis</i> binding to mucins correlated with glycans containing sulfate, sialic acid and terminal galactose. Among the glycolipids present in pig stomach, binding to lactotetraosylceramide (Galβ3GlcNAcβ3Galβ4Glcβ1Cer) was identified, and adhesion to Galβ3GlcNAcβ3Galβ4Glc at both acidic and neutral pH was confirmed using other glycoconjugates. Together with that <i>H. suis</i> bound to DNA (used as a proxy for acidic charge), we conclude that <i>H. suis</i> has two binding modes: one to glycans terminating with Galβ3GlcNAc, and one to negatively charged structures. Identification of the glycan structures <i>H. suis</i> interacts with can contribute to development of therapeutic strategies alternative to antibiotics.