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Microbial Toxins pp 247–265Cite as

Helicobacter pylori CagA: The Bacterial Oncoprotein

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Part of the book series: Toxinology ((TOXI))

Abstract

Helicobacter pylori infects the human stomach, causing atrophic gastritis, peptic ulcer, and gastric cancer. Among the virulence factors of H. pylori, the cag pathogenicity island (cag PAI) has been identified in the H. pylori genome, coding for several proteins that constitute a type IV secretion system (T4SS), whose main function is to inject bacterial factors into the host cell. In particular, CagA protein, encoded by cytotoxin-associated gene A (cagA) that is part of the cag PAI, is injected into the host cell in a T4SS-dependent manner. CagA, once into the cell, can be phosphorylated by host enzymes. Both phosphorylated and non-phosphorylated CagA initiate a series of intracellular events, which may dramatically interfere with cell morphology, motility, polarity, proliferation, and differentiation, leading to invasive phenotypes of host cells. Thereby, CagA has earned the definition of “bacterial oncoprotein.” Epidemiological studies in humans, as well as studies in animals infected with CagA-positive H. pylori strains, or in transgenic mice expressing CagA, indicated a clear link between CagA and the development of precancerous lesions and eventually gastric cancer. Although, besides CagA, other H. pylori factors have been linked to gastric cancer development, CagA appears to be the major agent responsible for the H. pylori-related carcinogenicity. The development of malignancy is also linked to host factors, such as proinflammatory genetic background. It might be expected that treatments or vaccines targeting CagA, even in the case they only partially affected the H. pylori burden, would decrease the risk of malignant outcome of the infection.

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Authors and Affiliations

  1. GSK Vaccines, Preclinical R&D, 53100, Siena, Italy

    Paolo Ruggiero

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  1. Paolo Ruggiero
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Correspondence to Paolo Ruggiero .

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Editors and Affiliations

  1. Biology Department, Wilson College, Chambersburg, Pennsylvania, USA

    Brad Stiles

  2. Department of Biochemistry, School of Medicine and Instituto Clodomiro Picado, Faculty of Microbiology, University of Costa Rica, San Pedro de Montes de Oca, Costa Rica

    Alberto Alape-Girón

  3. Department of Pathology and Microbiology, Université de Montréal, Saint-Hyacinthe, Québec, Canada

    J. Daniel Dubreuil

  4. College of Pharmacy, Roseman University of Health Sciences, Henderson, Nevada, USA

    Manas Mandal

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Ruggiero, P. (2018). Helicobacter pylori CagA: The Bacterial Oncoprotein. In: Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6449-1_22

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