Diversity of the cagA gene of Helicobacter pylori strains from patients with gastroduodenal diseases in the Philippines (original) (raw)
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2019
Background: Helicobacter pylori is a Gram-negative bacillus that colonises only the mucus layer of the human stomach and is implicated in gastric diseases. Virulent H. pylori harbouring cag-pathogenicity island (cagPAI) which encodes genes for type IV secretion system (T4SS) and CagA protein is one of the major virulence determinants involved in disease development. We examined the entire cagPAI genes in 95 H. pylori isolates from a multiracial population and examined the intactness of cagPAI region with histopathological scores of the gastric mucosa. Results: 95.8% of H. pylori isolates were cagPAI-positive with 23.2% having an intact cagPAI, whereas 72.6% had a partial/rearranged cagPAI. In our study, cag2 and cag4 were found to be signi cantly higher in H. pylori isolated from Malays, whereas cag4 was
Journal of Clinical Microbiology, 2009
The pathogenesis of gastroduodenal diseases is related to the diversity of H elicobacter pylori strains. CagA-positive strains are more likely to cause gastric cancer than CagA-negative strains. Based on EPIYA (Glu-Pro-Ile-Tyr-Ala) motifs at the carboxyl terminus corresponding to phosphorylation sites, H. pylori CagA is divided into East Asian CagA and Western CagA. The former type prevails in East Asia and is more closely associated with gastric cancer. The present study used full sequences of the cagA gene and CagA protein of 22 H. pylori strains in gastric cancer and peptic ulcer patients from Southern Vietnam to make a comparison of genetic homology among Vietnamese strains and between them and other strains in East Asia. A phylogenetic tree was constructed based on full amino acid sequences of 22 Vietnamese strains in accordance with 54 references from around the world. The cagA gene was found in all Vietnamese H. pylori strains. Twenty-one of 22 (95.5%) strains belonged to the...
Helicobacter pylori virulence and the diversity of gastric cancer in Asia
Journal of Medical Microbiology, 2008
Infection with cagPAI positive strains of Helicobacter pylori is recognized as being associated with an increased risk of gastric cancer. This article reviews the current knowledge on the structures and pathological functions of cagPAI and the CagA protein, focusing especially on the molecular mechanism through which CagA may be involved in gastric carcinogenesis. The possible link between the geographical distribution of cagPAI and cagA variations and gastric cancer diversity in Asia is also discussed.
Cancer Epidemiology Biomarkers & Prevention, 2011
Background: Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis. Methods: We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain. Results: A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathologic analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif. Conclusions: CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk. Impact: These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not. Cancer Epidemiol Biomarkers Prev; 20(10); 2237-49. Ó2011 AACR.
Journal of Gastroenterology and Hepatology, 2010
Background and Aims: The 3′ region of the cagA gene, the most well-known virulence factor of Helicobacter pylori, contains Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Four segments flanking the EPIYA motifs, EPIYA-A, -B, -C, or -D, were reported to play important roles in H. pylori-related gastroduodenal pathogenesis. The aim was to determine the roles of EPIYA segments in gastroduodenal pathogenesis in an Iranian population.Methods: A total of 92 cagA-positive Iranian strains isolated from dyspepsia patients with non-ulcer dyspepsia (n = 77), peptic ulcer (n = 11) and gastric cancer (n = 4) were studied. The EPIYA motif genotyping was determined by polymerase chain reaction and sequencing.Results: A total of 86 (93.5%) strains had three copies of EPIYA (ABC type), three (3.3%) had four copies (ABCC type) and three (3.3%) had two copies (AB type). The alignment of the deduced protein sequences confirmed that there were no East Asian type EPIYA-D sequences (EPIYATIDFDEANQAG) in Iranian strains. When the prevalence of strains with multiple EPIYA-C segments in Iran was compared with previously published data, it was much lower than that in Colombia and Italy, but was higher than that of Iraq, and the patterns were parallel to the incidence of gastric cancer in these countries.Conclusion: The structure of the 3′ region of the cagA gene in Iranian strains was Western type. Although we could not find differences between EPIYA types and clinical outcomes, low prevalence of strains with multiple EPIYA-C segments might be reasons for low incidence of gastric cancer in Iran.
Microbial Pathogenesis, 2014
The association between gastric cancer and Helicobacter pylori has been well established. Among H. pylori virulence genes the most important determinant is the cytotoxin associated antigen gene (cagA) which is characterized by the presence of repeated EPIYA motifs at the C terminus of the protein. From the alignment and number of these EPIYA motifs, two major types of CagA protein have been identified. Aims: The aim of this study was to classify the CagA into eastern or western type and to determine the number and type of motifs present. Methods: The CagA subtyping was done by PCR and multiplex PCR for eastern/western classification and determination of EPIYA motifs respectively. Results: All the isolates studied were of the western type, with 70% of the isolates having more than one EPIYA-C motifs. No statistically significant association was found between the presence of CagA and more than one EPIYA-C motifs with the clinical outcome (differentiation status of the tumour).
Clinical and Vaccine Immunology, 2001
Nucleic acid amplification was performed for five loci in thecag pathogenicity island (PAI) of Helicobacter pylori (comprising cagA, the cagApromoter region, cagE, cagT, and the left end of cagII [LEC]), and gastric inflammation in patients was evaluated. Of 204 H. pylori isolates from Japanese patients (53 with peptic ulcer, 55 with gastric cancer, and 96 with chronic gastritis), 197 (96.6%) were positive for all five loci. Two isolates (1%) were negative for all five loci, and five isolates (2.4%) were positive for only cagA and LEC. These latter seven isolates were all from patients with mild chronic gastritis. Neutrophil infiltration in gastric mucosa was significantly milder in patients infected with partially or totally deleted-PAI strains than in those with intact-PAI strains. The cagE gene was a more accurate marker of an intact cag PAI than thecagA gene, and cagE seemed to be more useful in discriminating between H. pylori strains causing different rates of disease progress...
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.