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Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients
Khansa Ben Mansour, Chédlia Fendri, Meriem Zribi, Afef Masmoudi, Mounir Labbene, Azza Fillali, Nabil Ben Mami, Taoufik Najjar, Ahmed Meherzi, Tahar Sfar, Christophe Burucoa
Annals of Clinical Microbiology and Antimicrobials , 2010, DOI: 10.1186/1476-0711-9-10
Abstract: H. pylori was cultured from endoscopic biopsies obtained from 281 Tunisian patients. The vacA alleles, cagA, iceA and oipA genotypes were determined by PCR.The vacA s1m1, s1m2 and s2m2 were respectively found in 10.7%, 12.5% and 45.6% of strains. The s2m1 genotype was not detected in our study. The cagA was found in 61.6% of isolates. The iceA1 and the iceA2 genotypes were respectively isolated in 60.2% and in 16% of strains. The oipA genotype was detected in 90.8% of strains. Considering the vacA and iceA genotypes, the presence of multiple H. pylori strains in a single biopsy specimen was found respectively in 31.4% and 23.8%. The comparison between strains isolated from antrum and fundus showed that Tunisian patients were infected with two or more strains of different cagA, vacA, iceA and oipA genotypes and the discordance was respectively in 9.6%, 4.6%, 8.9% and 8.5% of strains.Our results showed that in 46% (131 strains among 281), the H. pylori strains were highly virulent in relation of the three or four virulent factors they could carry. These finding were described before in the literature. Tunisian patients were colonized by one or multiple strains of H. pylori in the same time in relation of presence of vacA m1/m2 and iceA1/iceA2 in the same biopsy. The discordance between strains isolated from antrum and fundus was high, and it is in favour of multicolonization.Helicobacter pylori (H. pylori) is one of the most common bacterial pathogens of humans and has a worldwide distribution. Infection by H. pylori is associated with the development of chronic gastritis, gastric or duodenal ulcer, gastric cancer and MALT-lymphoma [1]. Different virulence genes have been described in H. pylori infection such as cagA, vacA, iceA and oipA genes. The cytotoxin-associated gene (cagA) is frequently associated with cytotoxin production and the induction of interleukin 8 (IL8) by gastric epithelial cells [2]. Several studies have suggested that cagA is a useful marker for t
Helicobacter pylori cagA and vacA genotypes in Cuban and Venezuelan populations
Ortiz-Princz, Diana;Guariglia-Oropeza, Verónica;ávila, Maira;Correnti, María;Perrone, Marianella;Gutierrez, Beatriz;Torres, Javier;Megraud, Francis;Cavazza, María Eugenia;
Memórias do Instituto Oswaldo Cruz , 2010, DOI: 10.1590/S0074-02762010000300016
Abstract: the aim of this study was to determine the presence of helicobacter pylori cytotoxin-associated gene (caga)/vacuolating cytotoxin gene (vaca) among patients with chronic gastritis in cuba and venezuela. gastric antrum biopsies were taken for culture, dna extraction and pcr analysis. amplification of vaca and caga segments was performed using two regions of caga: 349 bp were amplified with the f1/b1 primers and the remaining 335 bp were amplified with the b7629/b7628 primers. the va1-f/va1-r set of primers was used to amplify the 259-bp (s1) or 286-bp (s2) product and the vag-r/vag-f set of primers was used to amplify the 567-bp (m1) or 642-bp (m2) regions of vaca. caga was detected in 87% of the antral samples from cuban patients and 80.3% of those from venezuelan patients. all possible combinations of vaca regions were found, with the exception of s2/m1. the predominant combination found in both countries was s1/m1. the percentage of caga+ strains was increased by the use of a second set of primers and a greater number of strains was amplified with the b7629/b7628 primers in the cuban patients (p = 0.0001). there was no significant difference between the presence of the allelic variants of vaca and caga in both populations. the predominant genotype was caga+/s1m1 in both countries. the results support the necessary investigation of isolates circulating among the human population in each region.
Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases
Cavalcante, Meyssa Quezado de Figueiredo;Silva, Cicero Igor Sim?es;Braga-Neto, Manuel Bonfim;Fialho, Andréa Bessa Campelo;Nunes Fialho, André;Barbosa, Alzira Maria C;Cruz, Francisco Will Saraiva;Rocha, Gifone A;Queiroz, Dulciene Maria Magalh?es de;Braga, Lucia Libanez Bessa Campelo;
Memórias do Instituto Oswaldo Cruz , 2012, DOI: 10.1590/S0074-02762012000400021
Abstract: helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. in this study, we evaluated the helicobacter pylori vaca and caga genotypes in patients from a brazilian region where there is a high prevalence of gastric cancer. polymerase chain reaction (pcr) was used to investigate vaca mosaicism and caga status in the gastric mucosa of 134 h. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. the s1m1 variant was the predominant vaca genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with h. pylori infection [p = 0.03, odds ratio (or) = 5.72, 95% confidence interval (ci) = 1.15-38.60]. furthermore, all of the s1 alleles were s1b. mixed vaca m1/m2 strains were found more frequently in patients with gastric cancer and a caga-positive status was significantly associated with gastric cancer (p = 0.016, or = 10.36, 95% ci = 1.35-217.31). patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent h. pylori strains compared to gastritis patients (41/61, 67.2%). in conclusion, in the northeastern of brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent h. pylori strains, carrying the caga gene and s1m1 vaca alleles, predominates and is correlated with more severe h. pylori-associated diseases.
High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer  [PDF]
Yolanda López-Vidal, Sergio Ponce-de-León, Gonzalo Castillo-Rojas, Rafael Barreto-Zú?iga, Aldo Torre-Delgadillo
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003849
Abstract: Background Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. Methodology/Principal Findings Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. Conclusion/Significance High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.
Prevalence of Helicobacter pylori vacA, cagA, dupA and oipA Genotypes in Patients with Gastric Disease  [PDF]
Mayara Luciana Sallas, Jessica Lima Melchiades, Luanna Munhoz Zabaglia, Juliana Ribeiro do Prado Moreno, Wilson Aparecido Orcini, Elizabeth Suchi Chen, Marilia de Arruda Cardoso Smith, Spencer Luiz Marques Pay?o, Lucas Trevizani Rasmussen
Advances in Microbiology (AiM) , 2017, DOI: 10.4236/aim.2017.71001
Abstract: Gastric diseases such as chronic gastritis and gastric cancer are most commonly caused by virulence factors of Helicobacter pylori (H. pylori), such as the vacA, cagA, dupA and oipA genes. Therefore, this study investigated the prevalence and the combination of these virulence factors from patients with gastric diseases. The endoscopic biopsies were obtained from 516 patients with gastric symptoms, 101 of which were from patients with normal gastric tissue, 365 of which were from patients with chronic gastritis, and 50 of which were from patients with gastric cancer. H. pylori and the virulence factors were detected by PCR. The oipA gene exhibited an increased risk for chronic gastritis (p = 0.0296), and the vacA gene demonstrated a risk for gastric cancer from chronic gastritis (p = 0.0002). Based on the combination of the virulence factors, cagA, vacA, dupA and oipA genes exhibited a high prevalence in patients with chronic gastritis and gastric cancer. The cagA+/dupA+ genotype demonstrated a significant correlation in patients with normal gastric mucosa (p = 0.0278). In the chronic gastritis group, a significant association was observed between the cagA+ and the vacA s1m1 genotypes (p < 0.0001), the cagA+/dupA+ genotypes (p = 0.0183), the dupA+/oipA+ genotypes (p < 0.0001), and the dupA+/vacA s1m1 genotypes (p = 0.0008) genotypes. This study revealed a high prevalence of the combination of cagA, vacA, dupA, and oipA genes, which contributed to the risk of developing gastroduodenal diseases. Furthermore, this is the first study to reveal a high prevalence of the oipA gene in H. pylori isolates in Brazil.
Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden
Anneli Karlsson, Anna Ryberg, Marjan Nosouhi Dehnoei, Kurt Borch, Hans-Jurg Monstein
BMC Microbiology , 2012, DOI: 10.1186/1471-2180-12-129
Abstract: Variations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/d regions were analysed in 155?H. pylori-positive gastric biopsies from 71 individuals using PCR and sequencing. Analysis of a possible association between cagA and vacA genotypes and gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the same biopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs was associated with atrophy in the gastric mucosa. No statistically significant relation between vacA genotypes and gastroduodenal pathogenesis was observed.The results of this study indicate that cagA genotypes may be important determinants in the development of gastroduodenal sequelae of H. pylori infection. In contrast to other studies, vacA genotypes were not related to disease progression or outcome. In order to fully understand the relations between cagA, vacA and gastroduodenal pathogenesis, the mechanisms by which CagA and VacA act and interact need to be further investigated.
Determination of the Status of Helicobacter pylori sabA Gene in Relation to Clinical Findings  [cached]
Hossein Goudarzi,Hanieh Rezaee,Mitra Rafizadeh,Afsoon Taghavi
Journal of Medical Bacteriology , 2012,
Abstract: Background: Many Helicobacter pylori strains express adhesin proteins that bind to specific host-cell macromolecule receptors, like sialic acid binding adhesion (sabA). SabA-expressing strains have been associated with gastric cancer and negatively associated with duodenal ulcers. The aim of this study was to determine the status of sabA gene of H. pylori and its association with the clinical diseases in Iranian dyspeptic pateints. Methods: Eighty six biopsy block samples that were positive for H. pylori according Geimsa staining were included in this study. Genomic DNA was extracted from paraffin-embedded gastric biopsies obtained from dyspeptic patients. The identity of Helicobacter genus was determined through amplification of 16S rRNA which followed by sabA PCR using the gene-specific primers. The prevalence of sabA gene in three clinical groups including gastritis, gastric ulcer, and gastric atrophy was determined. The association of sabA gene and clinical outcomes was assessed statistically using Chi-square test. A p-value less than <0.05 was considered statistically significant. Results: Total of 86 patients was included in this study. Seventeen cases out of 86 (23.6%) were yielded a positive result for sabA gene. The prevalence of sabA gene was 28.6% in both dyspeptic and Gastric atrophy patients as compared with peptic ulcers (19.2%). Conclusion: For a first time the frequency of sabA gene using PCR methods was reported. The current study demonstrated that the sabA gene status was not associated with clinical diseases. In limited number of studied samples, higher frequency of sabA gene among dyspeptic and atrophic patients was found.
Determination of the Status of Helicobacter Pylori SabA Gene in Relation to Clinical Findings  [cached]
Hossein Goudarzi,Hanieh Rezaee,Mitra Rafizadeh,Afsoon Taghavi
Journal of Medical Bacteriology , 2012,
Abstract: Background: Many Helicobacter pylori strains express adhesin proteins that bind to specific host-cell macromolecule receptors, like sialic acid binding adhesion (sabA). SabA-expressing strains have been associated with gastric cancer and negatively associated with duodenal ulcers. The aim of this study was to determine the status of sabA gene of H. pylori and its association with the clinical diseases in Iranian dyspeptic pateints.Methods: Eighty six biopsy block samples that were positive for H. pylori according Geimsa staining were included in this study. Genomic DNA was extracted from paraffin-embedded gastric biopsies obtained from dyspeptic patients.The identity of Helicobacter genus was determined through amplification of 16S rRNA which followed by sabA PCR using the gene-specific primers. The prevalence of sabA gene in three clinical groups including gastritis, gastric ulcer, and gastric atrophy was determined. The association of sabA gene and clinical outcomes was assessed statistically using Chi-square test. A p-value less than <0.05 was considered statistically significant.Results: Total of 86 patients was included in this study. Seventeen cases out of 86 (23.6%) were yielded a positive result for sabA gene. The prevalence of sabA gene was 28.6% in both dyspeptic and Gastric atrophy patients as compared with peptic ulcers (19.2%).Conclusion: For a first time the frequency of sabA gene using PCR methods was reported. The current study demonstrated that the sabA gene status was not associated with clinical diseases. In limited number of studied samples, higher frequency of sabA gene among dyspeptic and atrophic patients was found.
MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy  [PDF]
Sara K. Lindén ,Yong H. Sheng,Alison L. Every,Kim M. Miles,Emma C. Skoog,Timothy H. J. Florin,Philip Sutton,Michael A. McGuckin
PLOS Pathogens , 2009, DOI: 10.1371/journal.ppat.1000617
Abstract: The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the α- and β-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy.
Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis  [cached]
Sahara Shu,Sugimoto Mitsushige,Vilaichone Ratha-Korn,Mahachai Varocha
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-223
Abstract: Background Infection with cagA-positive, cagA EPIYA motif ABD type, and vacA s1, m1, and i1 genotype strains of Helicobacter pylori is associated with an exacerbated inflammatory response and increased risk of gastroduodenal diseases. However, it is unclear whether the prevalence and virulence factor genotypes found in Southeast Asia are similar to those in Western countries. Here, we examined the cagA status and prevalence of cagA EPIYA motifs and vacA genotypes among H. pylori strains found in Southeast Asia and examined their association with gastroduodenal disease. Methods To determine the cagA status, cagA EPIYA motifs, and vacA genotypes of H. pylori, we conducted meta-analyses of 13 previous reports for 1,281 H. pylori strains detected from several Southeast Asian countries. Results The respective frequencies of cagA-positive and vacA s1, m1, and i1 genotypes among examined subjects were 93% (1,056/1,133), 98% (1,010/1,033), 58% (581/1,009), and 96% (248/259), respectively. Stratification showed significant variation in the frequencies of cagA status and vacA genotypes among countries and the individual races residing within each respective country. The frequency of the vacA m-region genotype in patients infected with East Asian-type strains differed significantly between the northern and southern areas of Vietnam (p < 0.001). Infection with vacA m1 type or cagA-positive strains was associated with an increased risk of peptic ulcer disease (odds ratio: 1.46, 95%CI: 1.01-2.12, p = 0.046 and 2.83, 1.50-5.34, p = 0.001, respectively) in the examined Southeast Asian populations. Conclusions Both Western- and East Asian-type strains of H. pylori are found in Southeast Asia and are predominantly cagA-positive and vacA s1 type. In Southeast Asia, patients infected with vacA m1 type or cagA-positive strains have an increased risk of peptic ulcer disease. Thus, testing for this genotype and the presence of cagA may have clinical usefulness.
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