Virulence Factors of Helicobacter pylori Responsible for Gastric Diseases in Mongolian Gerbil

Abstract

Helicobacter pylori infection induces various gastroduodenal diseases. We examined the role of two genes, vacA and cagE, in the gastric pathogenesis induced by H. pylori using a long-term (62 wk) animal model. Reportedly, both genes are associated with the virulence of H. pylori: vacA encodes vacuolating cytotoxin, and cagE, with other genes in the cag pathogenicity islands, encodes a type IV secretion system. Mongolian gerbils were challenged in this study by a wild-type TN2 strain and its isogenic mutants of cagE or vacA. The wild-type and vacA mutants induced severe gastritis, whereas cagE mutants induced far milder changes. Gastric ulcer was induced at the highest rate (22/23) by the wild-type TN2, followed by the vacA mutant (19/28). No ulcer was found in the gerbils infected with the cagE mutant (0/27) or in controls (0/27). Intestinal metaplasia was also found in the gerbils infected with the wild-type (14/23) or vacA mutant (15/28). Gastric cancer developed in one gerbil with wild-type infection and in one with vacA mutant infection. In conclusion, the knocking out of the cagE gene deprived wild-type H. pylori of the pathogenicity for gastritis and gastric ulcer, suggesting that the secretion system encoded by cag pathogenicity island genes plays an essential role.

Pattern of Transcription Factor Activation in Helicobacter pylori–Infected Mongolian Gerbils

“…The WT strain TN2GF4 induced an antral-dominant gastritis, whereas the cagE mutants induced little inflammation. These results are in agreement with previous studies using the same strain 11 as well as with strain TN2, which shares the same origin 20,27 as TN2GF4 and strain 24 ATCC43504. These results differ from experiments using strain B128 as the parental strain.…”

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

“…The cagA gene is a marker for a large 40-kb locus containing .40 genes, termed the cag pathogenicity island (cag PAI), and the majority of these genes encode membrane-associated proteins with features similar to other bacterial secretion systems, particularly the type IV system epitomised by Bordetella pertussis toxin secretion [27][28][29]. A cagE mutant induced only mild inflammation in Mongolian gerbils, whereas the wild-type strain and vacA mutants induced more severe gastritis [30].…”

“…A cagE mutant induced only mild inflammation in Mongolian gerbils, whereas the wild-type strain and vacA mutants induced more severe gastritis [30]. Mutation of cagE abolishes the ability of H. pylori to induce the cytokine interleukin-8 (IL-8), a neutrophil chemotactic factor, in Kato-3 cells [27,29,31,32]. Adherence has been shown to play a role in the induction of H. pyloriassociated IL-8 secretion [33].…”

Association of Helicobacter pylori Vacuolating Toxin (VacA) with Lipid Rafts

“…In a mouse model, a VacA-producing strain exhibited an enhanced capacity to colonize the stomach compared with an isogenic vacA-mutant strain, particularly in co-infection experiments (6). Studies in mouse and gerbil models also have suggested that VacA contributes to gastric mucosal injury (7,8). Analyses of H. pylori isolates from humans have revealed that strains isolated from patients with peptic ulcer disease typically produce VacA proteins with detectable cytotoxic activity in vitro (encoded by vacA alleles belonging to the type s1 family), whereas strains isolated from patients with no history of peptic ulcer disease commonly produce VacA proteins that lack detectable cytotoxic activity in vitro (encoded by vacA alleles belonging to the type s2 family) (9 -14).…”