Helicobacter pylori cagA+ Strains and Dissociation of Gastric Epithelial Cell Proliferation From Apoptosis (original) (raw)
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Basrah Journal of Surgery, 2010
This study aimed to learn the incidence of Helicobacter pylori infection in patients with various gastroduodenal endoscopic lesions and the frequency of virulence H.pylori associated genes CagA and VacA in these patients. One hundred seventy six patients (96 males and 80 females) attending endoscopy units for various dyspeptic symptoms were studied. Antral biopsies were obtained to detect H.pylori by rapid urease test, culturing and histopathologic examination. Twenty five patients with positive H.pylori isolates who were found to be mannose resistant, were tested for cytotoxic associated (CagA) and vacuolating cytotoxin A (VacA) genes. Among studied patients, positive H.pylori detected by rapid urease test, culturing and histopathologic examination (from 50 patients only) were 113 (63%), 127 (71%) and 25 (50%) respectively. Out of 25 patients with positive H.pylori isolates who were found to be mannose resistant, positive genes of either CagA or VacA were detected in 18 (72%) patients with positive isolates, while positivity of both genes were detected in 13(52%) patients with positive isolates. Five (45.4%) and 5 (45.4%) out of patients with duodenal ulcers and gastritis respectively were positive for both (CagA) and (VacA) genes. In conclusion, the highest detection rate of H.pylori infection was by bacterial culture. A correlation between CagA and VacA genes and endoscopic lesions of duodenal ulcers and gastritis was found.
Archives of Clinical Infectious Diseases, 2017
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.
2005
Helicobacter pylori has been strongly associated with gastritis, gastric and duodenal ulcers, and it is a risk factor for gastric cancer. Two major virulence factors of H. pylori have been described: the cytotoxin-associated gene product (cagA) and the vacuolating toxin (vacA). Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to determine if there is a significant correlation between different H. pylori virulence genes (cagA and vacA) in 68 patients, from Saudi Arabia, and gastric clinical outcomes. H. pylor was recognized in cultures of gastric biopsies. vacA and cagA genes were detected by polymerase chain reaction (PCR). The cagA gene was obtained with 42 isolates (61.8%). The vacA sand m-region genotypes were determined in all strains studied. Three genotypes were found: s1/m1 (28%), s1/m2 (40%) and s2/m2 (26%). The s2/m1 genotype was not found in this study. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (P < 0.05). The study showed a significant correlation between the vacA s1/m2 genotype and gastritis cases, and a significant correlation between vacA s1/m1 genotype and peptic ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacA s1/m1 genotype of H. pylori strains. In conclusion, H. pylori strains of vacA type s1 and the combination of s1/m1 were associated with peptic ulceration and the presence of cagA gene.
Helicobactor pylori (H. pylori) has been strongly associated with gastritis, peptic ulcer and is linked to an increased risk of gastric cancer. The cytotoxin-associated gene product (cagA) and the vacuolating cytotoxin (vacA) have been implicated as two major virulence factors of H. pylori. Since there is an increasing evidence that genetic variability of H. pylori may have clinical importance, we aimed to evaluate different vacA genotypes and reveal its relationship with endoscopic and transmission electron microscopy (TEM) findings among H. pylori infected Egyptian patients. Forty H. pylori infected patients possessing vacA gene who underwent upper endoscopic examination were considered to be infected with H. pylori when rapid urease test and detection of 16S rRNA in gastric biopsy recorded positive. Both vacA and cagA genotypes were detected by polymerase chain reaction (PCR). The TEM was performed to assess the ultra-structure of the gastric mucosa. Four vacA genotypes were identified, the most prominent was the s2/m2 allele combination (52.5%) followed by s1/m1 (27.5%), s1/m2 (17.5%) and s2/m1 genotype was found just in one H. pylori strain (2.5%). There were significant correlations between vacA s2/m2 and gastritis (65.2%), and vacA s1/m1 and peptic ulceration (57%). The cagA gene was associated with 38% of vacA genotypes and 60% of which were significantly associated with vacA s1/m1 genotype with the development of severe gastritis reaching up to gastric ulcer. The TEM revealed H. pylori spiral and coccoid forms, cytoplasmic vacuolar degeneration caused by vacA, swollen mitochondria and dilated rough endoplasmic reticulum. In Egypt where prevalence of H. pylori infection is high, genotyping of H. pylori virulence factors can help to predict patients who are at a high risk of related gastroduodenal diseases. Although H. pylori with vacA s2/m2 genotype is mostly related to low level of virulent strains yet, significant crosstalk between H. pylori strains harboring both vacA s1/m1 and cagA gene provides crucial insights into virulence of high level.
Sao Paulo Medical Journal, 2005
CONTEXT AND OBJECTIVE: The virulence of Helicobacter pylori (HP) in gastroduodenal disease is related to pathogenicity islands (cagPAI) present in some strains. Infection with cagPAI induces IL-8 secretion, increases epithelial cell proliferation and may be important in carcinogenesis. Our objective was to detect HP and the cagA gene (cagPAI marker) by polymerase chain reaction (PCR) and to correlate these results to histological findings, epithelial cell proliferation and apoptosis. DESIGN AND SETTING: Retrospective, at the Surgical and Molecular Pathology Laboratory, Hospital Sírio-Libanês. METHODS: DNA samples isolated from 164 gastric biopsies were used for HP detection by PCR. cagPAI+ was identified in HP+ cases by cagA gene amplification. All cases were submitted to immunohistochemistry to evaluate cell proliferation, and TUNEL to detect apoptosis. Statistical analysis was performed to compare results. RESULTS: HP was detected in 67.7% of the patients, with good correlation be...
Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike
Gastric carcinoma (GC) develops in only 1%-3% of Helicobacter pylori (H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta (IL-1β) group and tumour necrosis factor-alpha (TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability (MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes (such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.
Biomedical and Pharmacology Journal, 2017
Helicobacter pylori infection (H. pylori) is associated with gastric carcinoma and various of gastrointestinal disease. The prevalence of H. pylori infection in Indonesia is still controversial. There is no data about H. pylori Bali isolates and the Cag A virulence factor from patients with dyspepsia in Bali. H. pylori Bali isolates provided from Laboratorium of Microbiology, Biomedical Research Unit, West Nusatenggara General Hospital, which have been isolated from gastric antral biopsies collected from 3 gastric ulcer Balinese patients. This research revealed that all of three H. pylori Bali isolates examined positive for CagA (Cytotoxin associated antigen A) gene. Based on the result of the gel electrophoresis, a 640 bp single band observed similar in each sample. All H. pylori Bali isolates have EPIYA-ABD motif with unique motifs EPIYT on second EPIYA sequence. Three of H. pylori Bali isolates named as BLI 01, BLI 02 and BLI 03 that have a CagA genes. All the H. pylori Bali isolates have an unique EPIYT motifs (substitution A to T) in CagA genes. The degree of gastric inflammation is more severe in the 4 th week of the study. There was a significant difference of gastric inflammation degree in all of three groups of mice. H. pylori BLI 03 isolate with positive CagA gene, have a greatest degree of inflammation.