<em>Helicobacter pylori</em> SabA Adhesin in Persistent Infection and Chronic Inflammation
Abstract
Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis × glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis × antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid–binding adhesin (SabA) was isolated with the “retagging” method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.
Helicobacter pylori persistently infects the gastric mucosa of more than half of all people worldwide, causes peptic ulcer disease, and is an early risk factor for gastric cancer (1). Many H. pylori strains express adhesin proteins that bind to specific host-cell macromolecule receptors (2). This adherence may be advantageous to H. pylori by helping to stabilize it against mucosal shedding into the gastric lumen and ensuring good access to nourishing exudate from gastric epithelium that has been damaged by the infection. The best defined H. pylori adhesin-receptor interaction found to date is that between the Leb blood group antigen binding adhesin, BabA, a member of a family of H. pylori outer membrane proteins, and the H, Lewis b (Leb), and related ABO antigens (3-5). These fucose-containing blood group antigens are found on red blood cells and in the gastrointestinal mucosa (6). Blood group–O individuals suffer disproportionately from peptic ulcer disease, suggesting that bacterial adherence to the H and Leb antigens affects the severity of infection (7). Additional H. pylori–host macromolecule interactions that do not involve Leb-type antigens have also been reported (8).
H. pylori is a genetically diverse species, with strains differing markedly in virulence. Strains from persons with overt disease generally carry the cag-pathogenicity island (cag-PAI) (9, 10), which mediates translocation of CagA into host cells, where it is tyrosine phosphorylated and affects host cell signaling (11). Leb antigen binding is most prevalent among cag strains from persons with overt disease (4, 12). Separate studies using transgenic mice that express the normally absent Leb antigen suggest that H. pylori adherence exacerbates inflammatory responses in this model (13). Taken together, these results point to the pivotal role of H. pylori adherence in development of severe disease.
Footnotes
Supporting Online Material
www.sciencemag.org/cgi/content/full/297/5581/573/DC1
Materials and Methods
References and Notes
References
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