Abstract
Various gram-negative pathogens express type IV secretion systems (T4SSs) which translocate bacterial virulence factors into host target cells to hijack cellular processes for their own benefit and causing disease. The pathology of Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric cancer in humans, strongly depends on a T4SS encoded by the cag pathogenicity island (cagPAI). This T4SS represents a pilus-like structure and a membrane-spanning complex. T4SS assembly is achieved by various protein–protein interactions and several pilus-associated components (CagL, CagI, CagY, and CagA) that allow docking to the host cell integrin member α5β1 followed by delivery of its major effector protein, CagA, across the host cell membrane. In addition, recent studies have shown that H. pylori exploits human CEACAM receptors via the adhesin HopQ, encoded outside of the cagPAI, for bacterial adherence and translocation of CagA. Here, we review the composition and assembly of the H. pylori T4SS and its fundamental role in the infection process. We discuss major CagA-dependent and CagA-independent signaling events by the T4SS in vitro and in animal models in vivo, which include the induction of cytoskeletal rearrangements, membrane dynamics, disturbance of cell polarity as well as transcriptional responses involved in inflammation, cell proliferation, and anti-apoptosis. The contribution of these signaling cascades to H. pylori colonization, and pathogenesis is reviewed.
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Acknowledgements
We thank Drs. Timothy Cover (Vanderbilt University, Nashville, USA), Hayley Newton (University of Melbourne, Australia), and Wolfgang Fischer (Pettenkofer Institute, Munich, Germany) for comments on the manuscript. We also thank Drs. Manfred Rohde (Helmholtz Centre for Infection Biology, Braunschweig, Germany) for the electron microscopic image in Fig. 2, Timothy Cover for the electron microscopic images in Fig. 3c/d, and Laurent Terradot (University of Lyon, France) for the CagA structure in Fig. 4. This work was supported by the German Science Foundation to S.B. (A04 in CRC-1181), to R.H. (B05 in CRC-914), and M.N. (A04 in CRC-854).
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Backert, S., Haas, R., Gerhard, M., Naumann, M. (2017). The Helicobacter pylori Type IV Secretion System Encoded by the cag Pathogenicity Island: Architecture, Function, and Signaling. In: Backert, S., Grohmann, E. (eds) Type IV Secretion in Gram-Negative and Gram-Positive Bacteria. Current Topics in Microbiology and Immunology, vol 413. Springer, Cham. https://doi.org/10.1007/978-3-319-75241-9_8
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