Pylori Virulence Genes Research Articles

Distinct Diversity ofvacA,cagA, andcagEGenes ofHelicobacter pyloriAssociated with Peptic Ulcer in Japan

Colonization of the stomach mucosa by Helicobacter pylori is a major cause of acute and chronic gastric pathologies in humans. Several H. pylori virulence genes that may play a role in its pathogenicity have been identified. The most important determinants are vacA and cagA in the cag pathogenicity island (cagPAI) genes. In the present study, to consider the association of molecular genetics between vacA and the cagPAI regarding clinical outcome, we selected H. pylori strains with various genotypes of vacA in Japan and sequenced full-length vacA, cagA, and cagE genes. Sequencing of vacA and cagA genes revealed variable size, whereas the cagE gene was well conserved among strains. Each of the phylogenetic trees based on the deduced amino acid sequences of VacA, CagA, and CagE indicated that all three proteins were divided into two major groups, a Western group and an East Asian group, and the distributions of isolates exhibited similar patterns among the three proteins. The strains with s2 and s1a/m1a vacA genotypes and the Western-type 3' region cagA genotype were classified into the Western group, and the strains with the s1c/m1b vacA genotype and the East Asian-type 3' cagA genotype were included in the East Asian group. In addition, the prevalence of infection with the Western group strain was significantly higher in patients with peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22) (chi2 = 12.64, P = 0.00057). These data suggest that the molecular genetics of vacA and cagPAI are associated and that the Western group with vacA and cagPAI genes is associated with peptic ulcer disease.

The plasticity region locus JHP947 is a pathogenicity marker found in Helicobacter pylori-associated gastric intestinal metaplasia

Helicobacter pylori (H. pylori) and Intestinal Metaplasia (IM) are each associated with an increased risk of gastric cancer. The H. pylori genome contains genes that are located in a zone called the “plasticity region “ (45 kb in strain J99 and 68 kb in strain 26695). This region is highly variable. We evaluated the status of certain loci (JHP940, JHP947 and HP986) as well as H. pylori virulence genes (cagA, and vacA) by polymerase chain reaction (PCR). A total of 40 gastric biopsies (antrum & corpus) were obtained. Eighteen samples from 12 patients were classified according to disease group as gastritis (G) and 22 samples from 19 patients as intestinal metaplasia based on histopathology findings. The results demonstrated that the jhp947 locus was completely linked with the presence of the cag pathogenicity island and was also significantly associated with the percancerous lesion IM when compared with gastritis. There is no association between jhp940 or HP986 and IM. Therefore, the jhp947 locus may be considered as a new H. pylori marker for disease outcome independent of the virulence genes.

Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome

The aim of this study was to evaluate whether there was any correlation between Helicobacter pylori-associated diseases and (1) H. pylori virulence genes or (2) IL-1B, IL-1RN, IFN-G, TNF-A, IL-10 genetic polymorphisms. Patients with non-cardia gastric cancer (NCGC, n = 129) or benign gastroduodenal diseases ( n = 792) were studied. IL-1RN intron 2 VNTR polymorphism (PCR), IL-1B −31 C/T (RFLP), the SNPs of IFN-G (+874 A/T), TNF-A (−1031 C/T, −857 C/T, −376 A/G, −308 A/G, −238 A/G), IL-10 (−1082 A/G, −819 C/T, −592 A/C) (Taqman chemistry) were studied. cagA, s1 and m1 vacA, were PCR amplified. Duodenal ulcer was more frequent in TNF-A −857 TT and in IL-1RN 1,2 subjects. TNF-A −857 TT genotype was also correlated with gastric ulcer. IL-10 −819 TT genotype was associated with intestinal metaplasia and NCGC. Antral inflammation was associated with TNF-A −1031 TT, while corpus activity with IL-10 −819 CC. H. pylori infection was associated with TNF-A −308 AG genotype, while IFN-G +874 AA genotype was associated with cagA. In conclusion, among host genetic factors contributing to H. pylori disease outcome, IFN-G +874 AA genotype favors cagA positive infections, TNF-A −857 TT duodenal ulcer while IL-10 −819 TT intestinal metaplasia and NCGC.

H. pylori Infection: Bacterial Virulence Factors and Cytokine Gene Polymorphisms as Determinants of Infection Outcome

ABSTRACTThe gram negative bacterium H. pylori infects the human stomach worldwide, invariably causing mucosal inflammation. In the majority of cases, H. pylori-associated gastritis remains the only clinical manifestation of the infection, which might cause, otherwise, peptic ulcer, gastric adenocarcinoma, or MALToma. The balance between the bacterial virulence machinery and the host response to the infection determines the different clinical outcomes. The main bacterial virulence factors comprise adhesins (BabA, SabA), the vacuolating cytotoxin VacA, and the products of cag pathogenicity island. The pattern of cytokine production in response to the infection is one of the main host determinants involved in limiting the infection outcome to gastritis or in favoring peptic ulcer or cancer onset. The polymorphisms of some cytokine genes (IL-1β, IL-1RN, TNF-α, IFN-γ) have been correlated with H. pylori-associated gastric adenocarcinoma or peptic ulcer, possibly because they influence the amount of cytokine production in response to H. pylori infection. This review focuses on the role of H. pylori virulence genes and on host cytokines' genes polymorphisms in determining clinical outcome to H. pylori infection.

Intracellular and interstitial expression of Helicobacter pylori virulence genes in gastric precancerous intestinal metaplasia and adenocarcinoma.

Gastric intestinal metaplasia (IM) and gastric cancer are associated with Helicobacter pylori, but the bacterium often is undetectable in these lesions. To unravel this apparent paradox, IM, H. pylori presence, and the expression of H. pylori virulence genes were quantified concurrently using histologic testing, in situ hybridization, and immunohistochemistry. H. pylori was detected inside metaplastic, dysplastic, and neoplastic epithelial cells, and cagA and babA2 expression was colocalized. Importantly, expression of cagA was significantly higher in patients with IM and adenocarcinoma than in control subjects. The preneoplastic "acidic" MUC2 mucin was detected only in the presence of H. pylori, and MUC2 expression was higher in patients with IM, dysplasia, and cancer. These novel findings are compatible with the hypothesis that all stages of gastric carcinogenesis are fostered by persistent intracellular expression of H. pylori virulence genes, especially cagA inside MUC2-producing precancerous gastric cells and pleomorphic cancer cells.

Virulence genes in Helicobacter pylori strains from West Bengal residents with overt H. pylori-associated disease and healthy volunteers.

We compared putative molecular markers of virulence (vacA, cagA, and iceA) of Helicobacter pylori strains isolated from 52 adult duodenal ulcer patients from West Bengal, India, with those of H. pylori strains isolated from 48 adult healthy volunteers from the same region. On the basis of genotyping by PCR, we conclude that the H. pylori strains isolated from the two study groups were indistinguishable and that there are geographic variations in the association of certain putative H. pylori virulence genes with clinical status.

Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia.

Helicobacter pylori infection outcome might depend on genotypic polymorphisms of both the bacterium and the host. We ascertained: (1) the functionality of H. pylori oipA gene; (2) the polymorphism of the hostinterleukin (IL-1beta) gene (-31 C/T) and of the IL-1RN gene (intron 2 VNTR); (3) the association between the above genes and the histological and pathological outcome of H. pylori infection. One hundred and sixty-five H. pylori positive and 137 H. pylori negative subjects (23 gastric adenocarcinoma, 58 peptic ulcer, 221 gastritis) were studied. oipA was sequenced, IL-1beta was RFLP analysed. Antral and body mucosal biopsies were histologically evaluated. Functional oipA genes were correlated with cagA gene; both genes were significantly associated with gastritis activity, peptic ulcer and gastric adenocarcinoma. In these patients heterozygousIL-1RN 1/2 and IL-1beta C/T genotypes were more frequent than in gastritis patients. Intestinal metaplasia was associated with cagA, functional oipA and IL-1RN 2 allele. In conclusion, peptic ulcer and the preneoplastic intestinal metaplasia are associated with H. pylori virulence genes and with IL-1RN 2 host allele. An interplay between bacterial virulence factors and cytokines genotypes, is probably the main route causing H. pylori infection to lead to benign mild disease, benign severe disease or preneoplastic lesions.

In situ expression of H. pylori virulence genes and of MUC2 and MUC5AC apomucins in the normal, precancerous and cancerous human stomach

In situ expression of H. pylori virulence genes and of MUC2 and MUC5AC apomucins in the normal, precancerous and cancerous human stomach

In situ expression of H. pylori virulence genes and of MUC2 and MUC5AC apomucins in the normal, precancerous and cancerous human stomach

In situ expression of H. pylori virulence genes and of MUC2 and MUC5AC apomucins in the normal, precancerous and cancerous human stomach

Genotypic, clinical, and demographic characteristics of children infected with Helicobacter pylori.

Helicobacter pylori isolates vary between geographic regions. Certain H. pylori genotypes may be associated with disease outcome. Thirty-eight children underwent diagnostic upper endoscopy at four medical centers and were retrospectively analyzed to determine if H. pylori virulence genes were associated with endoscopic disease severity, histologic parameters, and host demographics. The H. pylori virulence genotype was analyzed by a reverse hybridization line probe assay and type-specific PCR. Endoscopic ulcers or erosions were found in 17 (45%) patients, with 13 (34%) of these patients having antral nodularity. Histological gastritis, of varying severity, was present in all children. Four patients harbored more than one H. pylori strain: one subject had both cagA(+) and cagA-negative strains, while three patients harbored either two different cagA-negative strains (two children) or two cagA(+) strains (one child). There were 28 (74%) cagA(+) isolates; 19 were associated with the vacA s1b genotype, 7 were associated with the vacA s1a genotype, 1 was associated with the vacA s1c genotype, and 1 was associated with the s2 genotype. Of 14 cagA-negative isolates, 6 were vacA s2 genotype, 4 were vacA s1b, 3 were vacA s1a, and 1 was vacA s1c. Nine of ten (90%) Hispanics had similar H. pylori strains (vacA s1b,m1), and all Asian-Canadian children were infected by strains with vacA s1c genotype. No correlation between H. pylori strain and endoscopic or histopathologic abnormalities was found. This study provides a baseline framework of North American children and their H. pylori strains, serving as a powerful epidemiological tool for prospective investigations to better understand the transmission and evolution of diverse disease outcomes.

Identification of Helicobacter pylori virulence genes by insertion mutagenesis

Identification of Helicobacter pylori virulence genes by insertion mutagenesis