Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates

Kidd, Mark; Lastovica, Albert J.; Atherton, John C.; Louw, J. A.

doi:10.1136/gut.49.1.11

Cited by 47 publications

(38 citation statements)

References 29 publications

(21 reference statements)

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“…Ahmadzadeh et al represented 13 different cagPAI genotyptes among 21 cagPAI positive H. pylori strains in Iran (34).This diversity is also high in different geographic populations (11,(35)(36)(37). Correlation between integrity of cagPAI, types of EPIYA motifs, and disease outcome was confirmed by several studies (24,(38)(39)(40)(41)(42). However, there are studies that reported contrary results (43)(44)(45).…”

Section: Discussionmentioning

confidence: 93%

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

Fazeli

Alebouyeh

Tavirani

et al. 2017

Arch Clin Infect Dis

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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.

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Section: Discussionmentioning

confidence: 93%

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

Fazeli

Alebouyeh

Tavirani

et al. 2017

Arch Clin Infect Dis

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“…USA, 60% [7] ; Spain, 66% [26] ; and England, 68% [27] ) but lower than that reported in some East Asian studies, which encountered over 90% of cagApositive isolates (Table 4) [25,28] . In addition, a highly significant correlation was observed between cagA status and vacAs1 and vacAs1m1 genotypes (Table 2), which is commonly linked to an increase in H pylori virulence [13,14,29,30] . An association was also observed between the presence of the cagA gene and the babA2-positive genotype, due to the fact that most cagApositive isolates carried the babA2 allele.…”

Section: Vaca Allelesmentioning

confidence: 97%

Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates

Torres¹,

Melián²,

Moreno³

et al. 2009

WJG

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and seven isolates (82.3%) were babA2 -positive. A significant correlation was observed between vacAs1m1 a n d c a g A a n d b e t w e e n va c A s 1 m 1 a n d b a b A 2 genotypes (P < 0.001 and P < 0.05, respectively) and between babA2 genotype and cagA status (P < 0.05); but, no correlation was observed between vacAs1 and babA2 genotypes. Eighty five (65.4%) and 73 (56.2%) strains were type 1 (vacAs1 -cagA -positive) and "triplepositive" (vacAs1 -cagA -babA2 -positive), respectively, and their presence was significantly associated with duodenal ulcer (P < 0.01 and P < 0.001, respectively). CONCLUSION:The distribution of the main virulence factors in the Cuban strains in this study resembled that of the Western-type strains, and the more virulent H pylori isolates were significantly associated with duodenal ulcer, ulcer disease being the worst pathology observed in the group studied.

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“…The cagPAI is a 40-kb region originally acquired horizontally and inserted into the glutamate racemase gene (1,15); it is present in about 50 to 60% of H. pylori isolates from Western countries and in Ͼ90% of isolates from East Asian countries. Some studies have shown that severe gastroduodenal diseases are associated with H. pylori strains that harbor an intact cagPAI (11,22,24,26,29,32,33), whereas other studies could not find a relationship (7,25).…”

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confidence: 98%

Heterogeneity in the Activity of MexicanHelicobacter pyloriStrains in Gastric Epithelial Cells and Its Association with Diversity in thecagAGene

et al. 2007

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Helicobacter pylori CagA is translocated into gastric epithelial cells by a type IV secretion system and interacts with the Src homology 2 phosphatase, altering cell morphology. Multiple EPIYA motifs in CagA are associated with increased activity in cells and with gastric cancer. The aim of this work was to study the heterogeneity in activity in cells of multiple H. pylori single colonies isolated from a single patient and its association with polymorphism in cagA. The presence of cagA, cagE, cagT, and cag10 was studied with 318 H. pylori isolates from the antra and corpora of 18 patients. AGS gastric epithelial cells were infected with 75 isolates, and interleukin-8 (IL-8) secretion, cytoskeletal changes, CagA translocation, and tyrosine phosphorylation were measured. The cagA 3-variable region was sequenced for 30 isolates to determine the number and types of EPIYA motifs. Isolates from an individual stomach were usually genetically related and had quantitatively similar phenotypic effects on cells (IL-8 induction and cytoskeletal changes). However, strains from different patients with similar CagA EPIYA motif patterns varied widely in these phenotypes. Among isolates with an EPIYA-ABC pattern, the phenotype was variable: IL-8 induction ranged from 200 to 1,200 pg/ml, and morphological changes occurred in 20 to 70% of cells. In several cases, cagA sequence diversity appeared to explain the lack of CagA activity, as isolates with an EPIYA-ACC pattern or a modified B motif had reduced cell activity. cag pathogenicity island-positive H. pylori isolates displayed a high level of heterogeneity in the capacity to induce IL-8 secretion and morphological changes; an absent or modified B motif was associated with low activity.

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Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates

Cited by 47 publications

References 29 publications

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

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

Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates

Heterogeneity in the Activity of MexicanHelicobacter pyloriStrains in Gastric Epithelial Cells and Its Association with Diversity in thecagAGene

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