Helicobacter pylori exotoxins and gastroduodenal diseases associated with cytotoxic strain infection.
This paper describes the characteristics of exotoxins produced by Helicobacter pylori, and in particular the vacuolating toxin (VacA) and the cytotoxin-associated protein (CagA). The possible association between infection by strains of certain phenotypic or genomic types and the seriousness of gastroduodenal diseases is discussed. Helicobacter pylori induces various morphological changes in cells in vitro, but only infection by strains which induce cytovacuolation has been studied at present. In its native form, VacA is a protein aggregate made of subunits with a mass of 95 kDa. In vitro it stimulates a cellular v-type ATPase present on the endosomes and creates an acidic environment inside the vacuoles. It also alters in vitro a K(+)-dependent phosphatase activity and could impair the flux of sodium through the cells. Purified VacA causes ulceration in mice; experimental infection in mice with strains which also express the CagA protein causes gastric erosions, vacuolation and epithelial and stromal polymorphonuclear (PMN) cell infiltration. In vivo vacuolation can be observed in gastric cells from patients infected with type I (VacA-CagA positive) H. pylori. CagA is a protein of 128-140 kDa molecular weight, noncytotoxic and highly immunogenic. It is coexpressed in approximately 70% of cytotoxin-producing strains. In CagA positive strain infection, increased levels of interleukin-8 (IL-8) are secreted by the colonized gastric mucosa. Patients infected by cytotoxic strains and/or patients with anti-CagA antibodies are more likely to have active gastritis, and are more likely to develop peptic ulcer or gastric cancer. The different outcomes of infection could be determined by host factors, diet, or by the age at which infection is acquired.
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Institute of Internal Medicine, University of Siena, Policlinico Le Scotte, Italy.
D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D003603:Cytotoxins / Q000138:chemical synthesis / Q000502:physiology*; D005770:Gastrointestinal Neoplasms / Q000382:microbiology*; D016481:Helicobacter Infections; D016480:Helicobacter pylori / Q000737:chemistry* / Q000145:classification / Q000472:pathogenicity; D051379:Mice; D010437:Peptic Ulcer / Q000382:microbiology*; D013045:Species Specificity; D014617:Vacuoles / Q000502:physiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori