Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori
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Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori Steffen Backert1*†, Marguerite Clyne2† and Nicole Tegtmeyer1†
Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin b1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed. Keywords: Helicobacter pylori, adherence, adhesin, integrin, receptor, signalling, type IV secretion
Introduction H. pylori colonises the stomach of about half of the human world population, which is associated with chronic, often asymptomatic gastritis in all infected individuals. Depending on various criteria, more severe gastric diseases including peptic ulcer disease can occur in up to 10-15% of infected persons [1-3]. H. pylori infections are commonly diagnosed with a strong inflammatory response, but the bacteria evolved numerous mechanisms during evolution to avoid recognition and clearance by the host defence machineries, and if not treated with antibiotics, they can persist for life. H. pylori-induced gastritis is the strongest singular risk factor for developing cancers of the stomach; however, only a small proportion of infected individuals develop * Correspondence: [email protected] † Contributed equally 1 University College Dublin, School of Biomolecular and Biomedical Sciences, Science Center West, Belfield Campus, Dublin-4, Ireland Full list of author information is available at the end of the article
malignancy such as mucosa-associated lymphoid tissue (MALT) lymphoma and even gastric adenocarcinoma [1-3]. Gastric adenocarcinoma constitutes the second leading cause of cancer-associated death worldwide, and about 700,000 people die from this malignancy annually [3]. The clinical outcome of infection wi
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