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 β1 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.
Highlights
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
There are two classical virulence determinants expressed by H. pylori, the CagA protein encoded by the cytotoxinassociated genes pathogenicity island and the vacuolating cytotoxin (VacA)
Studies of host-bacterial interactions using their fundamental adhesins and the virulence factors CagA and T4SS have provided us with many detailed insights in processes connected to H. pylori colonisation and pathogenesis
Summary
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. There are two classical virulence determinants expressed by H. pylori, the CagA protein encoded by the cytotoxinassociated genes pathogenicity island (cagPAI) and the. We discuss the structure and function of the T4SS, and how it makes contact with host cell surface factors to inject the CagA effector protein. Among clinical strains of H. pylori considerable diversity in the expression of OMPs exists This is thought to reflect a selective pressure for bacterial adhesion which may differ both across and within infected individuals over time. It has been shown that some of the classical adhesion molecules discussed below act in conjunction with factors from the cagPAI in order to highjack several host cell processes including altered transcription, cytoskeletal rearrangements, opening of cell-to-cell junctions, onset of inflammation and others as summarized in a simplified model (Figure 1A)
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