Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA

<p>Abstract</p> <p>Background</p> <p><it>homB </it>encodes a <it>Helicobacter pylori </it>outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD) and was shown to induce activation of interleukin-8 secretion <it>in vitro</it>, as well as contributing to bacterial adherence. Its 90%-similar gene, <it>homA</it>, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with <it>homB </it>and <it>homA</it>, as well as with the <it>H. pylori </it>virulence factors <it>cagA</it>, <it>babA </it>and <it>vacA</it>, in 415 <it>H. pylori </it>strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated.</p> <p>Results</p> <p>Both <it>homB </it>and <it>homA </it>genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD), <it>homB</it>, <it>cagA </it>and <it>vacA </it>s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively), and <it>homA </it>was closely correlated with NUD (p = 0.072). In East Asian strains (n = 138, 73 PUD and 65 NUD), <it>homB </it>was found more frequently than <it>homA</it>, and none of these genes was associated with the clinical outcome.</p> <p>Overall, <it>homB </it>was associated with the presence of <it>cagA </it>(p = 0.043) and <it>vacA </it>s1 (p < 0.001), whereas <it>homA </it>was found more frequently in <it>cagA</it>-negative (p = 0.062) and <it>vacA </it>s2 (p < 0.001) strains.</p> <p>Polymorphisms in <it>homB </it>and <it>homA </it>copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the <it>homB </it>two-copy genotype and PUD was also observed, emphasizing the role of <it>homB </it>in the virulence of the strain.</p> <p>Conclusion</p> <p>The global results suggest that <it>homB </it>and <it>homA </it>contribute to the determination of clinical outcome.</p

Allelic diversity and phylogeny of homB, a novel co-virulence marker of Helicobacter pylori

<p>Abstract</p> <p>Background</p> <p>The <it>homB </it>gene is a <it>Helicobacter pylori </it>disease-marker candidate, strongly associated with peptic ulcer disease, while <it>homA</it>, its paralogue gene with 90% sequence identity, is correlated with non-ulcer dyspepsia. The HomB encoded outer membrane protein was shown to contribute to the proinflammatory properties of <it>H. pylori </it>and also to be involved in bacterial adherence.</p> <p>This study investigated the distribution of <it>homB </it>and <it>homA </it>genes in 455 <it>H. pylori </it>strains from East Asian and Western countries, and carried out sequence comparison and phylogenetic analyses.</p> <p>Results</p> <p>Both <it>homB </it>and <it>homA </it>genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains.</p> <p>Analysis of <it>homB </it>and <it>homA </it>sequences revealed diversity regarding the number of copies and their genomic localization, with East Asian and Western strains presenting different genotypes. Moreover, <it>homB </it>and <it>homA </it>sequence analysis suggests regulation by phase variation. It also indicates possible recombination events, leading to gene duplication or <it>homB</it>/<it>homA </it>conversion which may as well be implicated in the regulation of these genes. Phylogenetic reconstruction of <it>homB </it>and <it>homA </it>revealed clustering according to the geographic origin of strains. Allelic diversity in the middle region of the genes was observed for both <it>homB </it>and <it>homA</it>, although there was no correlation between any allele and disease. For each gene, a dominant worldwide allele was detected, suggesting that <it>hom</it>B/<it>hom</it>A allelic variants were independent of the geographical origin of the strain. Moreover, all alleles were demonstrated to be expressed <it>in vivo</it>.</p> <p>Conclusion</p> <p>Overall, these results suggest that <it>homB </it>and <it>homA </it>genes are good candidates to be part of the pool of <it>H. pylori </it>OMPs implicated in host-bacteria interface and also contributing to the generation of antigenic variability, and thus involved in <it>H. pylori </it>persistence.</p

Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between <it>H. pylori </it>CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis.</p> <p>Results</p> <p>The number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR = 3.08, 95% CI = 1.74 to 5.45, p < 10^-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p = 0.04) and intestinal metaplasia (p = 0.007). Furthermore, patients infected by <it>cag</it>A strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer.</p> <p>Conclusions</p> <p>Our results demonstrate that infection with <it>H. pylori </it>strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer.</p> <p>Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.</p

Prevalência da infecção pelo Helicobacter pylori em Fortaleza, Ceará

The prevalence of Helicobacter pylori infection was assessed in a randomly selected sample of individuals from low-income community in Fortaleza, Northeastern Brazil. Overall, 384 out of 610 participants (62.9%) were H. pylori positive. A 47.5% infection rate was found in subjects aged six months to 10 years old, increased to 73.3% in subjects aged 11-20 years and then continued to increase with age reaching up to 87% in those over 60 years old. After this age group, the prevalence decreased slightly. The prevalence of infection increased significantly with age (pA prevalência da infecção pelo Helicobacter pylori foi avaliada em amostra randomizada de indivíduos de uma comunidade urbana de baixa renda em Fortaleza, Estado do Ceará. O H. pylori foi detectado em 384 (62.9%) dos 610 participantes. A taxa de infecção foi de 47.5% em indivíduos com seis meses a 10 anos de idade, aumentou para 73.3% entre indivíduos com 11 a 20 anos, e continuou a aumentar com a idade, atingindo 87% naqueles com aproximadamente 60 anos. Após essa idade, a prevalência diminuiu discretamente. A prevalência da infecção aumentou significantemente com a idade (

Increased serum gastrin in patients with different clinical forms of Chagas disease coinfected with Helicobacter pylori

Trypanosoma cruzi and Helicobacter pylori (HP) are pathogens that cause chronic diseases and have been associated with hypergastrinemia. The aim of this study was to evaluate the fasting gastrin levels in patients with different clinical forms of Chagas disease (CD), coinfected or not by HP. The enrolled individuals were outpatients attending at the university hospital. HP infection was assessed by serology and 13C-urea breath test. Fasting serum gastrin concentration was measured by chemiluminescence assay. Gastric endoscopic and histological features were also evaluated. Associations between CD and serum gastrin level were evaluated in a logistical model, adjusting for age, gender and HP status. A total of 113 patients were evaluated (45 with Chagas disease and 68 controls). In the multivariate analysis, increasing serum gastrin levels (OR= 1.02; 95% CI= 1.01-1.12), increasing age (OR= 1.05; 95% CI= 1.02 - 1.09) and HP-positive status (OR = 2.88; 95% CI = 1.10 - 7.51) remained independently associated with CD. The serum gastrin levels were significantly higher in the group of patients with the cardiodigestive form (P = 0.03) as well as with digestive form (P = &lt;0.001) of Chagas disease than in the controls. In conclusion, patients with cardiodigestive and digestive clinical forms of CD have increased basal serum gastrin levels in comparison with controls. Moreover, we also demonstrated that H. pylori coinfection contributes to the hypergastrinemia shown in CD

Clarithromycin-resistant H. pylori primary strains and virulence genotypes in the Northeastern region of Brazil

The increase of H. pylori resistance to clarithromycin is a concern. This study evaluated the prevalence of H. pylori’s primary resistance to clarithromycin and its association with virulence factors in adult dyspeptic patients and asymptomatic children. The gastric mucosa from patients (153 gastritis, 24 gastric cancer, 21 peptic ulcer) and gastric juice obtained by string test from 24 H. pylori and 23S rRNA positive asymptomatic children were included. The clarithromycin resistance was assessed by TaqMan RT-PCR 23S rRNA point mutations, A2142G and/or A2143G, and H. pylori virulence markers by PCR. Overall, the clarithromycin resistance was 14.4% (32/222), 14.2% in adults, and 12% in children, whereas origin, gender, and disease were not distinctive factors. The most prevalent point mutation was A2143G (62.5%). The point mutation was significantly less frequent in cagA-positive (11.4%) than in cagA-negative (23.6%) strains (p=0.03 OR = 0.4 95%CI = 0.19 - 0.91) as well as in cagE-positive (10.2%), cagE-negative (21.2%) (p=0.03 OR: 0.4 I.C:0.20-0.91). No difference was found in iceA or vacA alleles genotypes. Primary resistance to clarithromycin was lower than that reported in Southeast Brazil. The cagA and cagE positive H. pylori samples have few point mutations suggesting that individuals infected with virulent strains may be more susceptible to anti-H. pylori treatment

Low prevalence of H. pylori Infection in HIV-Positive Patients in the Northeast of Brazil

<p>Abstract</p> <p>Background</p> <p>This study conducted in Northeastern Brazil, evaluated the prevalence of <it>H. pylori </it>infection and the presence of gastritis in HIV-infected patients.</p> <p>Methods</p> <p>There were included 113 HIV-positive and 141 age-matched HIV-negative patients, who underwent upper gastrointestinal endoscopy for dyspeptic symptoms. <it>H. pylori </it>status was evaluated by urease test and histology.</p> <p>Results</p> <p>The prevalence of <it>H. pylori </it>infection was significantly lower (p < 0.001) in HIV-infected (37.2%) than in uninfected (75.2%) patients. There were no significant differences between <it>H. pylori </it>status and gender, age, HIV viral load, antiretroviral therapy and the use of antibiotics. A lower prevalence of <it>H. pylori </it>was observed among patients with T CD4 cell count below 200/mm³; however, it was not significant. Chronic active antral gastritis was observed in 87.6% of the HIV-infected patients and in 780.4% of the control group (p = 0.11). <it>H. pylori </it>infection was significantly associated with chronic active gastritis in the antrum in both groups, but it was not associated with corpus chronic active gastritis in the HIV-infected patients.</p> <p>Conclusion</p> <p>We demonstrated that the prevalence of <it>H. pylori </it>was significantly lower in HIV-positive patients compared with HIV-negative ones. However, corpus gastritis was frequently observed in the HIV-positive patients, pointing to different mechanisms than <it>H. pylori </it>infection in the genesis of the lesion.</p