CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model.
ABSTRACT Helicobacter pylori causes various gastro-duodenal diseases, including gastric cancer. The CagA protein, an H. pylori virulence factor, induces morphological changes in host cells and may be associated with the development of peptic ulcer and gastric carcinoma. The present study has analysed the role of CagA protein in the pathogenesis of H. pylori infection in the Mongolian gerbil model. Mongolian gerbils were challenged with wild-type H. pylori strain TN2, which has a functional cag pathogenicity island or isogenic mutants with disrupted cagA (DeltacagA) or cagE (DeltacagE) genes. They were sacrificed at 7, 13, and 25 weeks after inoculation. Pathological changes of the gastric mucosa were determined and apoptosis was assessed by the TUNEL assay. Immunohistochemistry for PCNA, phospho-IkappaBalpha, and phospho-Erk was also performed. All of the bacterial strains colonized the gerbil stomach at similar densities; however, the DeltacagA mutant induced milder gastritis than did the wild type. The extent of apoptosis and lymphoid follicle formation in the epithelium appeared to depend on intact cagA. The DeltacagA mutant induced less phosphorylation of IkappaBalpha and Erk, and less expression of interferon-gamma and interleukin-1beta mRNA in the epithelium than did the wild type. It is concluded that CagA protein may be essential for the induction of severe gastritis in the Mongolian gerbil model.
Article: Helicobacter pylori with stronger intensity of CagA phosphorylation lead to an increased risk of gastric intestinal metaplasia and cancer[show abstract] [hide abstract]
ABSTRACT: Background: Nearly all Taiwanese H. pylori stains are cagA-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA) had an impact on the clinical diseases and histological outcomes in this area.
Article: Helicobacter pylori with stronger intensity of CagA phosphorylation lead to an increased risk of gastric intestinal metaplasia and cancer.[show abstract] [hide abstract]
ABSTRACT: Nearly all Taiwanese H. pylori stains are cagA-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA) had an impact on the clinical diseases and histological outcomes in this area. We enrolled 469 dyspeptic patients and prospectively obtained the gastric biopsy specimens and the H. pylori isolates. These patients were categorized according to the clinical diseases, such as duodenal ulcer, gastric ulcer, gastric cancer, and gastritis with or without intestinal metaplasia. Their gastric specimens were reviewed by the updated Sydney's system. Furthermore, a total of 146 patients were randomly selected from each clinical category for evaluation of their isolates' p-CagA intensity by in vitro AGS cells co-culture. The p-CagA was sparse in 30 (20.5%), weak in 59 (40.5%), and strong in 57 (39%) isolates. The isolates from the patients of gastric cancer or gastritis with intestinal metaplasia had stronger p-CagA intensity than those of gastritis without intestinal metaplasia (p ≤ 0.002). Moreover, the patients infected with isolates with strong or weak p-CagA intensity had a higher risk of gastric intestinal metaplasia (p < 0.05, odds ratio 3.09~15.26) than those infected with sparse p-CagA isolates. Infection with H. pylori stains with stronger p-CagA intensity may lead to an increased risk of gastric intestinal metaplasia and cancer.BMC Microbiology 01/2011; 11:121. · 3.04 Impact Factor
Article: Simultaneous Detection of Caga and Cage of Helicobacter pylori Strains Recovered from Iranian Patients with Different Gastroduodenal Diseases[show abstract] [hide abstract]
ABSTRACT: Background: To asses the status of two representative genes of cag PAI i.e cagA and cagE of Helicobacter pylori strains infecting Iranian patients suffered from various clinical outcomes using one-step PCR. Methods: A total of 120 H. pylori infected patients including non–ulcer dyspepsia, NUD (n=81), peptic ulcer disease, PUD (n=17), and gastric carcinoma, GC (n= 22) referred for endoscopy or gastric resection to AmirAlam Hospital or Cancer Institute from 2005 to 2008 were assessed. The status of cagA and cagE genes was determined by gene specific PCR. Results: 84.2% and 90.8% of the tested strains were positive for cagA and cage, respectively. 81.7% strains were positive for both cagA and cagE genes, whereas 8 (6.7%) were found double negative. The prevalence of cagA in GC patients (100%) was slightly higher than PUD patients (94.1%). All of GC cases were infected with cagA-positive strains. The same distribution pattern was indicated for cagE gene in GC and PUD patients. The cagA-positive strains were significantly associated with GC as compared with NUD (P< 0.05) but this association did not gain statistical significance when cagE gene was assessed. Conclusion: The concurrent detection of cagA/cagE genes allowed rapid and specific clarification of cag PAI status. The strains with cagA/cagE genotype are predominant in Iran regardless of clinical outcome and create a distinct cluster pattern from those in the West and similar to those of East Asian countries. The current study also demonstrated that cagE gene can be explored as a better indication of cag-PAI in Iranian H. pylori strains.Iranian J Publ Health. 01/2009; 38:98-105.