Functional Cytotoxin Associated Gene A in Helicobacter pylori Strains and Its Association with Integrity of Cag-pathogenicity Island and Histopathological Changes of Gastric Tissue

Abstract

Objectives: Existence of cytotoxin associated gene A (cagA) is considered as a marker for detection of an oncogenic Helicobacter pylori strain. Expression of cagA in the strains with incomplete delivery system (partial CagPAI) could convert them to less virulent strains.This study was aimed to analyze expression of cagA in H. pylori strains presenting diverse cagPAI and its effect on histopathological changes of the gastric tissue. Methods: Clinical strains of H. pylori and related histopathological data were obtained to examine the presence of 12 cagPAI segments by PCR. Expression of cagA was analyzed by RT-PCR as well as Immunoblotting on RNA and protein extracts of the cagPAIpositive strains, respectively. In situe expression of CagA-positive strains was determined in a gastric epithelial cell line. Results: Intact cagPAI was detected among 33% (4/12) of H. pylori strains. Out of 7 diverse cagPAI genotypes in these strains, expression of cagA was confirmed in 2 strains with complete cagPAI at both RNA and protein levels. Occurrence of intestinal metaplasia and severe active gastritis were mainly detected in the strains with complete cagPAI genotype. No association was detected between EPIYA types of the strains and expression of cagA. Conclusions: These results collectively showed high diversity of cagA and cagPAI among the H. pylori strains. These diversities may provide some reasons to explain distinct disease severity caused by different H. pylori strains in the gastric tissue.

Investigate the influence of a CagA-negative Helicobacter pylori strain, GD13, on nonhomologous end joining-mediated repair of proximal DNA double-strand breaks in GCV6 cells

“…Notably, the 26695 strain promoted significantly more IL-8 than did the GD13 strain. Our data are consistent with those of previous studies showing that CagA is a determining factor in the induction of IL-8 release and that CagA induces IL-8 in fibroblasts via a pathway similar to that in AGS cells 21,22 . Our data also showed that NHEJmediated repair of DSBs decreased in cells infected with the 26695 strain but remained at a similar level in cells infected with the GD13 strain.…”

Functional Analysis of cag Pathogenicity Island Diversity in Helicobacter pylori Isolated from Multi-Ethnic Patients in Malaysia

“…The majority of the strains in our study showed partially deleted cagPAI genotype (61.9%), a similar to those of previous studies (Ahmadzadeh et al 2015;Alfizah et al 2013;Hanafiah et al 2020). As explained in a previous study (Hanafiah et al 2020), the lack of intactness in the cagPAI within these strains was due to different gene detection method having been used in the other study (Fazeli et al 2017). As in other studies, cagPAI might not be conserved as deletions within islands can occur, and socio-demographic and geographical factors also play essential roles in the variation of cagPAI diversity in H. pylori (Olbermann et al 2010;Ta et al 2012).…”

Investigation of Campylobacter concisus gastric epithelial pathogenicity using AGS cells

“…H. pylori strain 26695, a human gastric pathogen, was used as a positive control in this study (Ashktorab et al, 2008;Fazeli et al, 2016). H. pylori strain 26695 was cultured on HBA plates at 37 o C under microaerobic conditions generated using CampyGen 2.5L Atmosphere Generation System (Thermo Fisher Scientific) for 48 h before being used in experiments.…”