Four Modes of Adhesion are Used During Helicobacter pylori Binding to Human Mucins in the Oral and Gastric Niches

Abstract

Background: Helicobacter pylori causes peptic ulcer disease and gastric cancer, and the oral cavity is likely to serve as a reservoir for this pathogen. We investigated the binding of H. pylori to the mucins covering the mucosal surfaces in the niches along the oral to gastric infection route and during gastric disease and modeled the outcome of these interactions. Materials and Methods: A panel of seven H. pylori strains with defined binding properties was used to identify binding to human mucins from saliva, gastric juice, cardia, corpus, and antrum of healthy stomachs and of stomachs affected by gastritis at pH 7.4 and 3.0 using a microtiter-based method. Results: H. pylori binding to mucins differed substantially with the anatomic site, mucin type, pH, gastritis status, and H. pylori strain all having effect on binding. Mucins from saliva and gastric juice displayed the most diverse binding patterns, involving four modes of H. pylori adhesion and the MUC5B, MUC7, and MUC5AC mucins as well as the salivary agglutinin. Binding occurred via the blood-group antigen-binding adhesin (BabA), the sialic acid-binding adhesin (SabA), a charge/low pH-dependent mechanism, and a novel salivabinding adhesin. In the healthy gastric mucus layer only BabA and acid/ charge affect binding to the mucins, whereas in gastritis, the BabA/Le

Lack of Association of Common Polymorphisms in MUC1 Gene with H. pylori Infection and Non-cardia Gastric Cancer Risk in a Chinese Population

“…Upon infection, H. pylori primarily resides within the mucus layer, adhering to mucins, high molecular weight glycoproteins and major components of the protective layer across the upper mucous surfaces (Peek and Blaser, 2002;Lindén et al, 2008). Some works have documented the role of MUC1 in the H. pylori infection and gastric cancer risk.…”

Common Genetic Variations in the MUC5AC Gene are Not Related to Helicobacter pylori Serologic Status

“…pylori colonization of the stomach is initiated through pathogen binding to cell surface receptors expressing the sialyl-Lewis a (sLea), Lewis b (Leb), and sialyl-Lewis x (sLex) glycoconjugates (Lindén et al, 2008). The corresponding H. pylori adhesions, blood group antigen binding adhesion (BabA) and sialic acid binding adhesion (SabA), interact with these host receptors (Lindén et al, 2008).…”

“…Normal gastric mucosa shows cell type specific expression of secreted mucin MUC5AC in the surface epithelium (Wang et al, 2006;Lindén et al, 2010). Several studies have strongly suggested that MUC5AC forms the major receptor for H. pylori in the human stomach (Van de Bovenkamp et al, 2003;Lindén et al, 2008), and the infection of H. pylori can alter the expression of MUC5AC (Kocer et al, 2004).…”

Transfection of the Helicobacter�pylori CagA gene alters MUC5AC expression in human gastric cancer cells

“…Adhesion to the gastric mucosa is important in the life cycle of H. pylori (4). As MUC5AC is an important receptor for gastric mucosa adhesion (5-7), efficient colonization of the stomach requires high expression of MUC5AC by gastric epithelial cells (8,9). Previous studies have demonstrated that the stomach epithelium reacts to H. pylori infection by activating pro-inflammatory signaling pathways (10), thereby activating innate defense mechanisms against H. pylori, which may include the downregulation of MUC5AC expression in the human gastric mucosa (2,6,11,12).…”