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Roles of the cagPAI and CagA on Gastroduodenal Diseases

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Helicobacter pylori Research

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Abstract

Helicobacter pylori is a highly successful human-specific Gram-negative bacterium. Infections with this pathogen in the stomach can induce pathologies ranging from chronic gastritis, peptic ulcers, to gastric cancer. Highly virulent H. pylori isolates harbor the cytotoxin-associated genes (cag) pathogenicity island, which encodes a typical type IV secretion system (T4SS). This T4SS constitutes a syringe-like pilus structure for the translocation of virulence factors such as the CagA effector protein into gastric epithelial and immune cells. This is achieved by a number of T4SS proteins such as CagL, CagI, CagY, and CagA, which can interact with the host cell integrin member α5β1 followed by transport of CagA across the host cell membrane. After delivery, CagA undergoes phosphorylation by oncogenic tyrosine kinases and mimics a host factor for the activation or inactivation of multiple intracellular signaling cascades. Here we review the current status in the characterization of phosphorylation-dependent and phosphorylation-independent signaling events by CagA and the CagA-independent T4SS activities in vivo and in vitro, which include the induction of membrane dynamics, actin-cytoskeletal rearrangements, disruption of cell-to-cell junctions, as well as pro-inflammatory, proliferative and anti-apoptotic nuclear responses. The contribution of these signaling pathways to pathogenesis during H. pylori infection is discussed.

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Authors and Affiliations

  1. Division of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nuremberg, Staudtstr. 5, D-91058, Erlangen, Germany

    Steffen Backert, Judith Lind, Carmen Isabell Asche & Nicole Tegtmeyer

  2. Department of Biomedical Sciences, University of Padua, Viale G. Colombo 3, 35131, Padova, Italy

    Giuseppe Zanotti

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  1. Steffen Backert
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  2. Giuseppe Zanotti
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  3. Judith Lind
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  4. Carmen Isabell Asche
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  5. Nicole Tegtmeyer
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Correspondence to Steffen Backert .

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  1. Division of Microbiology;Dept of Biology, Friedrich Alexander Univ;Erlangen-Nuremb, Erlangen, Bayern, Germany

    Steffen Backert

  2. Dept of Medicine-Gastroenteology, Baylor College of Medicine, Houston, USA

    Yoshio Yamaoka

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Backert, S., Zanotti, G., Lind, J., Asche, C.I., Tegtmeyer, N. (2016). Roles of the cagPAI and CagA on Gastroduodenal Diseases. In: Backert, S., Yamaoka, Y. (eds) Helicobacter pylori Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55936-8_4

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