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Review
. 2017 Oct 12;9(10):316.
doi: 10.3390/toxins9100316.

Helicobacter pylori Vacuolating Toxin and Gastric Cancer

Mark S McClain  1 , Amber C Beckett  2 , Timothy L Cover  3   4   5
Affiliations
Review

Helicobacter pylori Vacuolating Toxin and Gastric Cancer

Mark S McClain et al. Toxins (Basel). .

Abstract

Helicobacter pylori VacA is a channel-forming toxin unrelated to other known bacterial toxins. Most H. pylori strains contain a vacA gene, but there is marked variation among strains in VacA toxin activity. This variation is attributable to strain-specific variations in VacA amino acid sequences, as well as variations in the levels of VacA transcription and secretion. In this review, we discuss epidemiologic studies showing an association between specific vacA allelic types and gastric cancer, as well as studies that have used animal models to investigate VacA activities relevant to gastric cancer. We also discuss the mechanisms by which VacA-induced cellular alterations may contribute to the pathogenesis of gastric cancer.

Keywords: Helicobacter pylori; gastric cancer; pore-forming toxins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
vacA allelic diversity. Three main regions of vacA heterogeneity are recognized, designated as the signal or “s” region, the intermediate or “i” region, and the middle or “m” region. The sequences in each of these regions can be classified into two main families (s1 and s2; i1 and i2; m1 and m2). The figure illustrates the relationship of these regions to VacA p33 and p55 domains.
Figure 2
Figure 2
Sites of VacA action relevant to gastric cancer pathogenesis. H. pylori colonizes the mucus layer overlying foveolar/surface mucous epithelium and also enters gastric glands. (1) VacA causes multiple alterations in foveolar gastric epithelial cells. (2) Targeting of gastric stem cells by VacA may be a critical step in the pathogenesis of gastric cancer. (3) VacA inhibits acid secretion by parietal cells. Increased gastric pH allows other bacterial species to colonize the stomach. (4) VacA interferes with the function of multiple types of immune cells, potentially compromising their ability to function effectively in surveillance for malignant cells. (5) As a consequence of VacA targeting epithelial cells, tight junctions between gastric epithelial cells are disrupted. This potentially allows carcinogenic molecules to enter the gastric mucosa.
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