Abstract
Vacuolating cytotoxin A (VacA) is a secreted pore-forming toxin and one of the major virulence factors of Helicobacter pylori (H. pylori), which actively supports the persistence and survival of the bacteria in the special ecological niche of the human stomach. H. pylori genomes harbor different allelic forms of the vacA gene, which translate into functionally distinct VacA toxin types. VacA internalizes into various cell types via membrane or specific receptor interactions finally forming acidic endocytic VacA-containing vacuoles (VCVs). In this review, we focus on different characteristics of VacA, its interaction with host cells, the formation and protein content of VCVs and their intracellular transport into human T cells, which finally leads to the immunosuppressive phenotype of VacA. Immunomodulatory activities of VacA on human T cells are discussed with a focus on T-cell proliferation and calcium signaling.
Highlights
The human bacterial pathogen Helicobacter pylori (H. pylori), first cultured and identified in 1982, still infects more than 50% of the world’s population [1]
Several independent groups reported that Vacuolating cytotoxin A (VacA) tested in vivo caused a marked decrease in IL-2 secretion in the human Jurkat T-cell line, which was artificially stimulated by phorbol myristate acetate (PMA) [9,27,28]
We have learned much about the structure and function of the vacuolating toxin of H. pylori over the last quarter of a century
Summary
The human bacterial pathogen Helicobacter pylori (H. pylori), first cultured and identified in 1982, still infects more than 50% of the world’s population [1]. H. pylori contributes to the development of diseases such as gastritis, duodenal and gastric ulcers, and gastric cancer, earning it a place on the WHO list of class 1 carcinogens, even though only a minority of infected individuals develop clinical symptoms [2] It holds an impressive inventory of virulence factors, which enable the bacteria to persist in the human stomach and cause lifelong infections. The p33 N-terminal region contains a short residue sequence essential for vacuolating activities [14], and the p55 C-terminal region is important for the toxins’ target binding abilities. Both fragments are needed for internalization and vacuolation [15]. Bacterial mutants missing a 21 amino acid stretch (∆6-27aa) of this 32 amino acid region produce a VacA toxin that is incapable of causing vacuolation [14,16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
