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Helicobacter pylori pp 49–66Cite as

Helicobacter pylori VacA Exhibits Pleiotropic Actions in Host Cells

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Abstract

Helicobacter pylori vacuolating cytotoxin (VacA) is a major virulence factor, with pleiotropic actions on target cells including induction of vacuole formation, mitochondrial dysfunction leading to apoptosis, modulation of signal transduction pathways associated with autophagy, inhibition of T cell proliferation, and production of inflammatory cytokines. Numerous epidemiological studies have indicated that the allelic diversity within four variable regions of the vacA gene might be associated with cell type-specific binding as well as specific clinical outcomes in H. pylori infection. VacA binds to receptors such as receptor protein tyrosine phosphatases (RPTPα and RPTPβ), low-density lipoprotein receptor-related protein-1 (LRP1), fibronectin, CD18, and sphingomyelin to facilitate its action, suggesting the involvement of these receptors in the pathogenesis of H. pylori infection. RPTPβ contributes to ulceration in gastric epithelial cells and LRP1 is involved in the induction of autophagy. Interestingly, it has been suggested that CagA is degraded by VacA-induced autophagy and that the interaction between these two molecules is associated with the pathogenesis of gastric diseases. Therefore, better understanding of the mechanism of VacA toxicity may provide valuable information regarding appropriate medical care for gastroduodenal diseases caused by H. pylori infection.

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Acknowledgments

MN was supported by Takeda Science Foundation. TH and KY were supported by the Cooperative Research Grant of the Institute of Tropical Medicine, Nagasaki University, 2012 and 2014. JM was supported by the Intramural Research Program, National Institutes of Health, and National Heart, Lung, and Blood Institute. KY was also supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Improvement of Research Environment for Young Researchers from the Japan Science and Technology Agency.

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Authors and Affiliations

  1. Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan

    Masayuki Nakano & Toshiya Hirayama

  2. Cardiovascular and Pulmonary Branch, NHLBI, NIH, Bethesda, MD, USA

    Joel Moss

  3. Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Kinnosuke Yahiro

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  1. Masayuki Nakano
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  2. Toshiya Hirayama
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  3. Joel Moss
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  4. Kinnosuke Yahiro
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Correspondence to Masayuki Nakano .

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  1. Medical Education Center, Keio University School of Medicine, Tokyo, Japan

    Hidekazu Suzuki

  2. The Royal Perth Hospital, The University of Western Australia and, Western Australia, West Australia, Australia

    Robin Warren

  3. The Royal Perth Hospital, The University of Western Australia and, Western Australia, Australia

    Barry Marshall

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Nakano, M., Hirayama, T., Moss, J., Yahiro, K. (2016). Helicobacter pylori VacA Exhibits Pleiotropic Actions in Host Cells. In: Suzuki, H., Warren, R., Marshall, B. (eds) Helicobacter pylori. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55705-0_4

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  • DOI: https://doi.org/10.1007/978-4-431-55705-0_4

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