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  1. Novel CagA ELISA exhibits enhanced sensitivity of Helicobacter pylori CagA antibody

    PubMed Central

    Matsuo, Yuichi; Kido, Yasutoshi; Akada, Junko; Shiota, Seiji; Binh, Tran Thanh; Trang, Tran Thi Huyen; Dung, Ho D Q; Tung, Pham Huu; Tri, Tran Dinh; Thuan, Ngo P Minh; Tam, Le Quang; Nam, Bui Chi; Khien, Vu Van; Yamaoka, Yoshio

    2017-01-01

    AIM To develop a novel Helicobacter pylori (H. pylori) CagA antibody enzyme-linked immunosorbent assay (ELISA) suitable for detecting serum anti-CagA antibodies with high sensitivity. METHODS Recombinant East Asian-type CagA protein was purified and immobilized for ELISA. Serum samples from 217 Vietnamese individuals (110 H. pylori-infected and 107 uninfected individuals) were applied. Conventional ELISA from Western-type CagA and our East Asian-type CagA ELISA were evaluated by comparing 38 subjects with the Western-type genotype and 72 subjects with the East Asian-type cagA genotype. Histological scores of the gastric mucosa were determined using the updated Sydney System to examine the relationship with anti-CagA antibody titers. RESULTS Recombinant 70-100 kDa fragments were immobilized on the ELISA plate. In ROC analysis, the area under the curve of our East Asian-type CagA ELISA was comparable to that of conventional CagA ELISA. The sensitivity of the two ELISAs differed depending on the cagA genotype. The sensitivity of East Asian-type CagA ELISA was higher for subjects infected with East Asian-type cagA H. pylori (P < 0.001), and the sensitivity of the conventional CagA ELISA tended to be higher for subjects infected with Western cagA H. pylori (P = 0.056). The titer of anti-CagA antibody tended to correlate with monocyte infiltration scores (r = 0.25, P = 0.058) and was inversely correlated with H. pylori density (r = -0.26, P = 0.043). CONCLUSION The novel ELISA is useful to detect anti-CagA antibodies in East Asian countries, and the titer may be a marker for predicting chronic gastritis. PMID:28104980

  2. Helicobacter pylori cagA Promoter Region Sequences Influence CagA Expression and Interleukin 8 Secretion.

    PubMed

    Ferreira, Rui M; Pinto-Ribeiro, Ines; Wen, Xiaogang; Marcos-Pinto, Ricardo; Dinis-Ribeiro, Mário; Carneiro, Fátima; Figueiredo, Ceu

    2016-02-15

    Heterogeneity at the Helicobacter pylori cagA gene promoter region has been linked to variation in CagA expression and gastric histopathology. Here, we characterized the cagA promoter and expression in 46 H. pylori strains from Portugal. Our results confirm the relationship between cagA promoter region variation and protein expression originally observed in strains from Colombia. We observed that individuals with intestinal metaplasia were all infected with H. pylori strains containing a specific cagA motif. Additionally, we provided novel functional evidence that strain-specific sequences in the cagA promoter region and CagA expression levels influence interleukin 8 secretion by the host gastric epithelial cells.

  3. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection.

    PubMed Central

    Parsonnet, J; Friedman, G D; Orentreich, N; Vogelman, H

    1997-01-01

    BACKGROUND AND AIMS: It is not known why some people with Helicobacter pylori infection develop gastric cancer whereas others do not. Whether the CagA phenotype of H pylori infection affected risk for cancer independently of other posited risk factors was evaluated. SUBJECTS: 242 persons who participated in a previous nested case-control study of gastric cancer. 179 (90 cases and 89 controls) were infected with H pylori as determined by enzyme linked immunosorbent assay (ELISA) in serum and 63 (13 cases and 50 controls) were uninfected. METHODS: Serum samples from cases and controls, obtained a mean of 14.2 years before diagnosis of cancer in the cases, were tested by ELISA for IgG antibodies against the CagA gene product of H pylori. They had previously been tested for pepsinogen I. Using logistic regression analysis, risk for cancer was compared among infected persons with CagA antibodies, infected persons without CagA antibodies, and uninfected persons. RESULTS: Subjects infected with H pylori who had CagA antibodies were 5.8-fold more likely than uninfected subjects to develop gastric cancer (95% confidence interval (95% CI) = 2.6-13.0). This was true for both intestinal (odds ratio (OR) 5.1, 95% CI = 2.1-12.2) and diffuse type (OR 10.1, 95% CI = 2.2-47.4) cancers. By contrast, H pylori infected subjects without CagA antibodies were only slightly, and not significantly, at increased risk for cancer (OR 2.2, 95% CI = 0.9-5.4) and any possible association was restricted to diffuse type carcinoma (OR 9.0, 95% CI = 1.2-65.8). Pepsinogen 1 < 50 ng/ml significantly increased risk for both cancer types in H pylori infected persons and lessened the magnitude of association between CagA and cancer. Educational attainment, cigarette smoking, and ABO blood group were not associated with malignancy. CONCLUSIONS: When compared with uninfected subjects, persons infected with CagA positive H pylori are at considerably increased risk of gastric cancer. CagA negative H pylori

  4. Fragmentation of CagA Reduces Hummingbird Phenotype Induction by Helicobactor pylori.

    PubMed

    Chang, Chih-Chi; Kuo, Wein-Shung; Chen, Ying-Chieh; Perng, Chin-Lin; Lin, Hwai-Jeng; Ou, Yueh-Hsing

    2016-01-01

    Infection with Helicobacter pylori (H. pylori) has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.

  5. Dynamic Expansion and Contraction of cagA Copy Number in Helicobacter pylori Impact Development of Gastric Disease

    PubMed Central

    Su, Hanfu; Blum, Faith C.; Bae, Sarang; Choi, Yun Hui; Kim, Aeryun; Hong, Youngmin A.; Kim, Jinmoon; Kim, Ji-Hye; Gunawardhana, Niluka; Jeon, Yeong-Eui; Yoo, Yun-Jung; Merrell, D. Scott

    2017-01-01

    ABSTRACT Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori. Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8) induction. Sequence analysis of the repeat region revealed three cagA homologous areas (CHAs) within the cagA repeats. Of these, CHA-ud flanked each of the cagA copies and is likely important for the dynamic variation of cagA copy numbers. Analysis of a large panel of clinical isolates showed that 7.5% of H. pylori strains isolated in the United States harbored multiple cagA repeats, while none of the tested Korean isolates carried more than one copy of cagA. Finally, H. pylori strains carrying multiple cagA copies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction of cagA copy numbers may serve as a novel mechanism by which H. pylori modulates gastric disease development. PMID:28223454

  6. Regulation of Helicobacter pylori cagA expression in response to salt.

    PubMed

    Loh, John T; Torres, Victor J; Cover, Timothy L

    2007-05-15

    Helicobacter pylori infection and a high dietary salt intake are risk factors for the development of gastric adenocarcinoma. In this study, we tested the hypothesis that high salt concentrations might alter gene expression in H. pylori. Transcriptional profiling experiments indicated that the expression of multiple H. pylori genes, including cagA, was regulated in response to the concentrations of sodium chloride present in the bacterial culture medium. Increased expression of cagA in response to high salt conditions was confirmed by the use of transcriptional reporter strains and by immunoblotting. H. pylori CagA is translocated into gastric epithelial cells via a type IV secretion pathway, and on entry into target cells, CagA undergoes tyrosine phosphorylation and causes multiple cellular alterations. Coculture of gastric epithelial cells with H. pylori grown under high salt conditions resulted in increased tyrosine-phosphorylated CagA and increased secretion of interleukin-8 by the epithelial cells compared with coculture of the cells with H. pylori grown under low salt conditions. Up-regulation of H. pylori cagA expression in response to high salt concentrations may be a factor that contributes to the development of gastric adenocarcinoma.

  7. Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA

    PubMed Central

    Shimoda, Asako; Ueda, Koji; Nishiumi, Shin; Murata-Kamiya, Naoko; Mukai, Sada-atsu; Sawada, Shin-ichi; Azuma, Takeshi; Hatakeyama, Masanori; Akiyoshi, Kazunari

    2016-01-01

    CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA-positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA-positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA-positive H. pylori infection. PMID:26739388

  8. Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility.

    PubMed

    Poppe, M; Feller, S M; Römer, G; Wessler, S

    2007-05-24

    Helicobacter pylori induces a strong motogenic response in infected gastric epithelial host cells, which is enhanced by translocation of the pathogenic factor cytotoxin-associated gene A (CagA) into host cells via a specialized type IV secretion system. Once injected into the cytosol CagA is rapidly tyrosine phosphorylated by Src family kinases followed by Src inactivation. Hence, it remained unknown why CagA is constantly phosphorylated in sustained H. pylori infections to induce cell migration, whereas other substrates of Src kinases are dephosphorylated. Here, we identify the non-receptor tyrosine kinase c-Abl as a crucial mediator of H. pylori-induced migration and novel CagA kinase in epithelial cells. Upon H. pylori infection c-Abl directly interacts with CagA and localizes in focal adhesion complexes and membrane ruffles, which are highly dynamic cytoskeletal structures necessary for cell motility. Selective inhibition of c-Abl kinase activity by STI571 or shRNA abrogates sustained CagA phosphorylation and epithelial cell migration, indicating a pivotal role of c-Abl in H. pylori infection and pathogenicity. These results implicate c-Abl as a novel molecular target for therapeutic intervention in H. pylori-related gastric diseases.

  9. Helicobacter pylori CagA Inhibits PAR1-MARK Family Kinases by Mimicking Host Substrates

    SciTech Connect

    Nesic, D.; Miller, M; Quinkert, Z; Stein, M; Chait, B; Stebbins, C

    2010-01-01

    The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

  10. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    NASA Astrophysics Data System (ADS)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  11. Functional association between the Helicobacter pylori virulence factors VacA and CagA.

    PubMed

    Argent, Richard H; Thomas, Rachael J; Letley, Darren P; Rittig, Michael G; Hardie, Kim R; Atherton, John C

    2008-02-01

    The Helicobacter pylori virulence factors CagA and VacA are implicated in the development of gastroduodenal diseases. Most strains possessing CagA also possess the more virulent vacuolating form of VacA. This study assessed the significance of possession of both virulence factors in terms of their effect on gastric epithelial cells, using a set of minimally passaged, isogenic VacA, CagA and CagE mutants in H. pylori strains 60190 and 84-183. The cagA and cagE mutants were found to significantly increase VacA-induced vacuolation of epithelial cells, and the vacA mutants significantly increased CagA-induced cellular elongations, compared with wild-type strains, indicating that CagA reduces vacuolation and VacA reduces hummingbird formation. Although epithelial cells incubated with the wild-type H. pylori strains may display both vacuolation and hummingbird formation, it was found that (i) hummingbird length was significantly reduced in vacuolated cells compared with those without vacuolation; (ii) the number of vacuoles was significantly reduced in vacuolated cells with hummingbird formation compared with those without hummingbirds; and (iii) cells displaying extensive vacuolation did not subsequently form hummingbirds and vice versa. VacA did not affect the phosphorylation of CagA. These data show that VacA and CagA downregulate each other's effects on epithelial cells, potentially allowing H. pylori interaction with cells whilst avoiding excessive cellular damage.

  12. Helicobacter pylori CagA induced interleukin-8 secretion in gastric epithelial cells

    PubMed Central

    Fazeli, Zeinab; Alebouyeh, Masoud; Rezaei Tavirani, Mostafa; Azimirad, Masoumeh; Yadegar, Abbas

    2016-01-01

    Aim: Since, contradictory data have been reported about the effect of diverse variants of H. pylori virulence factors on IL-8 induction, we aimed to analyze the effect of this diversity on levels of IL-8 secretion in AGS cell line. Background: Helicobacter pylori colonizes the human stomach and induces the activation of inflammatory cytokines, including interleukin (IL)-8, in the gastric mucosa. This induction promotes neutrophil and monocyte recruitment that causes gastric tissue damage. Methods: To determine whether different strains of H. pylori and their CagA variants have possible roles on IL-8 induction, polarized AGS cell line was infected with CagA+ H. pylori strains carrying different EPIYA motifs (ABCCC and ABC) and CagA- strain for 24 hours. Difference in stimulation of IL-8 was measured by ELISA. Results: IL-8 secretion was elevated in the treated cells with CagA encoding strains compared with the negative one. Furthermore, a noticeably increased level of IL-8 induction was measured by the CagA-EPIYA type ABCCC encoding strain in compare to that carried EPIYA type ABC Conclusion: Results of this study provide new evidence about different effects of H. pylori strains and possible roles of their CagA variants on IL-8 induction. It seems that not only carriage of cagA and its expression, but also diversity in EPIYA motif be involved in IL-8 induction in the gastric epithelial cells. PMID:28224027

  13. Attenuation of Helicobacter pylori CagA x SHP-2 signaling by interaction between CagA and C-terminal Src kinase.

    PubMed

    Tsutsumi, Ryouhei; Higashi, Hideaki; Higuchi, Megumi; Okada, Masato; Hatakeyama, Masanori

    2003-02-07

    Helicobacter pylori (H. pylori) is a causative agent of gastric diseases ranging from gastritis to cancer. The CagA protein is the product of the cagA gene carried among virulent H. pylori strains and is associated with severe disease outcomes, most notably gastric carcinoma. CagA is injected from the attached H. pylori into gastric epithelial cells and undergoes tyrosine phosphorylation. The phosphorylated CagA binds and activates SHP-2 phosphatase and thereby induces a growth factor-like morphological change termed the "hummingbird phenotype." In this work, we demonstrate that CagA is also capable of interacting with C-terminal Src kinase (Csk). As is the case with SHP-2, Csk selectively binds tyrosine-phosphorylated CagA via its SH2 domain. Upon complex formation, CagA stimulates Csk, which in turn inactivates the Src family of protein-tyrosine kinases. Because Src family kinases are responsible for CagA phosphorylation, an essential prerequisite of CagA.SHP-2 complex formation and subsequent induction of the hummingbird phenotype, our results indicate that CagA-Csk interaction down-regulates CagA.SHP-2 signaling by both competitively inhibiting CagA.SHP-2 complex formation and reducing levels of CagA phosphorylation. We further demonstrate that CagA.SHP-2 signaling eventually induces apoptosis in AGS cells. Our results thus indicate that CagA-Csk interaction prevents excess cell damage caused by deregulated activation of SHP-2. Attenuation of CagA activity by Csk may enable cagA-positive H. pylori to persistently infect the human stomach for decades while avoiding excess CagA toxicity to the host.

  14. Prevalence of cagA EPIYA motifs in Helicobacter pylori among dyspeptic patients in northeast Thailand.

    PubMed

    Chomvarin, Chariya; Phusri, Karnchanawadee; Sawadpanich, Kookwan; Mairiang, Pisaln; Namwat, Wises; Wongkham, Chaisiri; Hahnvajanawong, Chariya

    2012-01-01

    The aims of this study were to determine the prevalence of cagA type in Helicobacter pylori isolated from dyspeptic patients in northeastern Thailand and to determine whether the pattern of cagA EPIYA motifs were associated with clinical outcomes. One hundred and forty-seven H. pylori-infected dyspeptic patients were enrolled, of whom 68 had non-ulcer dyspepsia (NUD), 57 peptic ulcer disease (PUD), 18 gastric cancer (GCA), and 4 other gastroduodenal diseases. PCR and DNA sequence analysis were used to determine the cagA genotype and the pattern of EPIYA motifs. cagA-positive H. pylori were identified in 138 (94%) of H. pylori-infected dyspeptic patients of whom 75 (54%) were of the Western-type, 44 (32%) the East Asian type and 19 (14%) of the other types. The Western type is significantly found in PUD patients (p = 0.0175). The majority of cagA EPIYA was EPIYA-ABC (43%) and EPIYA-ABD (28%). There is no significant correlation between the increase in number of EPIYA-C motifs and clinical outcomes. Thus, the most frequent cagA type found among northeastern Thai dyspeptic patients was the Western cagA type, which is significantly associated with PUD indicating a possible predictive parameter for clinical outcome.

  15. Helicobacter pylori CagA: analysis of sequence diversity in relation to phosphorylation motifs and implications for the role of CagA as a virulence factor.

    PubMed

    Evans, D J; Evans, D G

    2001-09-01

    CagA is transported into host target cells and subsequently phosphorylated. Clearly this is a mechanism by which Helicobacter pylori could take control of one or more host cell signal transduction pathways. Presumably the end result of this interaction favors survival of H. pylori, irrespective of eventual damage to the host cell. CagA is noted for its amino acid (AA) sequence diversity, both within and outside the variable region of the molecule. The primary purpose of this review is to examine how variation in the type and number of CagA phosphorylation sites might determine the outcome of infection by different strains of H. pylori. The answer to this question could help to explain the widely disparate results obtained when H. pylori CagA status has been compared to type and severity of disease outcome in different populations, that is in different countries. Analysis of all available CagA sequences revealed that CagA contains both tyrosine phosphorylation motifs (TPMs) and cyclic-AMP-dependent phosphorylation motifs (CPMs). There are two potential CPMs near the N-terminus of CagA and at least two in the repeat region; these are not all equally well conserved. We also defined a 48-residue AA sequence, which includes the N-terminal TPM at tyrosine (Y)-122, which distinguishes between Eastern (Hong Kong-Taiwan-Japan-Thailand) H. pylori isolates and those from the West (Europe-Africa-the Americas-Australia). All 28 of the Eastern type CagA proteins have a functional N-terminal TPM whereas 11 of 47 (23.4%) of the Western type contain an inactive motif, with threonine (T) replacing the critical aspartic acid (D) residue. Only 13 of 24 (54%) known CagA sequences have an active TPM in the repeat region and only one has two TPMs in this region. The potential TPM near the C-terminus of CagA is not likely to be important since only 3 of 24 (12.5%) sequences were found to be intact. Protein database searches revealed that the AA sequence immediately following the TPM at Y

  16. Diversity of the cagA gene of Helicobacter pylori strains from patients with gastroduodenal diseases in the Philippines.

    PubMed

    Cortes, Maria Celeste C; Yamakawa, Akiyo; Casingal, Cristine R; Fajardo, Lindsay Sydney N; Juan, Ma Luisa G; De Guzman, Blanquita B; Bondoc, Edgardo M; Mahachai, Varocha; Yamazaki, Yukinao; Yoshida, Masaru; Kutsumi, Hiromu; Natividad, Filipinas F; Azuma, Takeshi

    2010-10-01

    Helicobacter pylori CagA protein is considered a major virulence factor associated with gastric cancer. There are two major types of CagA proteins: the Western and East Asian CagA. The East Asian CagA-positive H. pylori infection is more closely associated with gastric cancer. The prevalence of gastric cancer is quite low in the Philippines, although Philippine populations are considered to originate from an East Asia source. This study investigates the characteristics of the cagA gene and CagA protein in Philippine H. pylori strains and compares them with previously characterized reference strains worldwide. The full-length cagA gene was sequenced from 19 Philippine isolates and phylogenetic relationships between the Philippine and 40 reference strains were analyzed. All Philippine strains examined were cagA positive, and 73.7% (14/19) strains were Western CagA-positive. The phylogenetic tree based on the deduced amino acid sequence of CagA indicated that the Philippine strains were classified into the two major groups of CagA protein: the Western and the East Asian group. These findings suggest that the modern Western influence may have resulted in more Western type H. pylori strains in the Philippines. Therefore, H. pylori-infected Filipinos can be considered to be at a low risk of developing gastric cancer.

  17. What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases

    PubMed Central

    da Costa, Débora Menezes; Pereira, Eliane dos Santos; Rabenhorst, Silvia Helena Barem

    2015-01-01

    Helicobacter pylori (H. pylori) infection is present in more than half the world’s population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma. The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cagA and vacA genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cagA-negative. Several other virulence genes have been searched for, but these genes remain less well known that cagA and vacA. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and iceA based on the relevance shown in several studies in the literature. PMID:26457016

  18. Clinical relevance of Helicobacter pylori vacA and cagA genotypes in gastric carcinoma.

    PubMed

    Ferreira, Rui M; Machado, José C; Figueiredo, Ceu

    2014-12-01

    Helicobacter pylori infection is the major etiological factor of gastric carcinoma. This disease is the result of a long, multistep, and multifactorial process, which occurs only in a small proportion of patients infected with H. pylori. Gastric carcinoma development is influenced by host genetic susceptibility factors, environmental factors, and H. pylori virulence. H. pylori is genetically highly variable, and variability that affects H. pylori virulence factors may be useful to identify strains with different degrees of pathogenicity. This review will focus on VacA and CagA that have polymorphic regions that impact their functional properties. The characterization of H. pylori vacA and cagA-associated could be useful for identifying patients at highest risk of disease, who could be offered H. pylori eradication therapy and who could be included in programs of more intensive surveillance in an attempt to reduce gastric carcinoma incidence.

  19. Geographic differences and the role of cagA gene in gastroduodenal diseases associated with Helicobacter pylori infection.

    PubMed

    Valmaseda Pérez, T; Gisbert, J P; Pajares García, J M

    2001-07-01

    Helicobacter pylori (H. pylori) is the major causal agent of gastritis, peptic ulcer and gastric cancer. Several bacterium genes seem to be involved in the pathogenicity mechanism. One of them, the cagA gene, has been extensively studied and characterized. In this article we have carried out a study of characteristics and genetic variability of cagA gene in different geographic areas of the world. At the same time, we have summarized several studies that evaluate possible relation of cagA with gastroduodenal diseases associated by H. pylori infection. In our study we found that the presence of the cagA gene has been confirmed in more than 60% H. pylori strains distributed throughout the world. The prevalence of cagA genotype is of 65.4% in gastritis patients, 84.2% in patients with peptic ulcer and 86.5% in those with gastric cancer. It shows a high genetic variability of cagA associated with gastroduodenal diseases that could serve as a virulence marker in H. pylori infected subjects. However, the high prevalence of H. pylori cagA positive strains in some geographic areas does not confirm the strong association between cagA and virulence of strains as described in other countries. Nowadays, cagA gene is considered as a marker for the presence of cag pathogenicity island (cag-PAI) in H. pylori genoma. This region contains several genes that has been involved with the production of cytokines that results in an increased inflammation of host gastric mucosa, but its function is unknown. Probably, others bacterium factors, such as susceptibility host and environmental cofactors could influence in the risk of developing different gastroduodenal diseases associated with H. pylori infection.

  20. The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression.

    PubMed

    J Lang, Ben; J Gorrell, Rebecca; Tafreshi, Mona; Hatakeyama, Masanori; Kwok, Terry; T Price, John

    2016-05-01

    Bacterial infections typically elicit a strong Heat Shock Response (HSR) in host cells. However, the gastric pathogen Helicobacter pylori has the unique ability to repress this response, the mechanism of which has yet to be elucidated. This study sought to characterize the underlying mechanisms by which H. pylori down-modulates host HSP expression upon infection. Examination of isogenic mutant strains of H. pylori defective in components of the type IV secretion system (T4SS), identified the secretion substrate, CagA, to be essential for down-modulation of the HSPs HSPH1 (HSP105), HSPA1A (HSP72), and HSPD1 (HSP60) upon infection of the AGS gastric adenocarcinoma cell line. Ectopic expression of CagA by transient transfection was insufficient to repress HSP expression in AGS or HEK293T cells, suggesting that additional H. pylori factors are required for HSP repression. RT-qPCR analysis of HSP gene expression in AGS cells infected with wild-type H. pylori or isogenic cagA-deletion mutant found no significant change to account for reduced HSP levels. In summary, this study identified CagA to be an essential bacterial factor for H. pylori-mediated suppression of host HSP expression. The novel finding that HSPH1 is down-modulated by H. pylori further highlights the unique ability of H. pylori to repress the HSR within host cells. Elucidation of the mechanism by which H. pylori achieves HSP repression may prove to be beneficial in the identification of novel mechanisms to inhibit the HSR pathway and provide further insight into the interactions between H. pylori and the host gastric epithelium.

  1. Association of Helicobacter pylori cagA Gene with Gastric Cancer and Peptic Ulcer in Saudi Patients.

    PubMed

    Saber, Taisir; Ghonaim, Mabrouk M; Yousef, Amany R; Khalifa, Amany; Al Qurashi, Hesham; Shaqhan, Mohammad; Samaha, Mohammad

    2015-07-01

    This study was conducted to assess the relationship between occurrence of gastric cancer and peptic ulcer, and the presence of H. pylori cagA gene and anti-CagA IgG, and to estimate the value of these antibodies in detecting infection by cagA gene-positive H. pylori strains in Saudi patients. The study included 180 patients who were subjected to upper gastrointestinal endoscopy in Taif province and Western region of Saudi Arabia (60 gastric cancer, 60 peptic ulcer, and 60 with non-ulcer dyspepsia). Gastric biopsy specimens were obtained and tested for H. pylori infection by rapid urease test and culture. PCR was performed on the isolated strains and biopsy specimens for detection of the cagA gene. Blood samples were collected and tested for CagA IgG by ELISA. H. pylori infection was detected among 72.8% of patients. The cagA gene and anti-CagA IgG were found in 63.4% and 61.8% of H. pylori-infected patients, respectively. They were significantly (p < 0.01) higher in patients with gastric cancer and peptic ulcer compared with those with non-ulcer dyspepsia. Detection of the CagA IgG was 91.6% sensitive, 89.6% specific, and 90.8% accurate compared with detection of the cagA gene. Its positive and negative predictive values were 93.8% and 86%, respectively. The study showed a significant association between the presence of the cagA gene and gastric cancer and peptic ulcer disease, and between anti-CagA IgG and the cagA gene in Saudi patients. However, a further larger study is required to confirm this finding.

  2. Development of a lateral flow immunoassay strip for rapid detection of CagA antigen of Helicobacter pylori.

    PubMed

    Karakus, Cebrail

    2015-01-01

    About half of the world populations are known to be infected with Helicobacter pylori. The CagA antigen secreting strains provoke severe mucosal damages and act as a risk factor for the development of peptic ulceration and gastric cancer. A lateral flow immunoassay (LFIA) strip was developed based on sandwich format for rapid detection of CagA antigen of H. pylori using gold conjugated monoclonal antibody. This LFIA strip will provide a good aid in the diagnosis of CagA-secreting H. pylori within 10 min instead of time consuming, expensive and laborious invasive approaches.

  3. Consensus and Variable Region PCR Analysis of Helicobacter pylori 3′ Region of cagA Gene in Isolates from Individuals with or without Peptic Ulcer

    PubMed Central

    Rota, Cláudia Augustin; Pereira-Lima, Júlio C.; Blaya, Carolina; Nardi, Nance Beyer

    2001-01-01

    The clinical outcome of Helicobacter pylori infection may be associated with the cagA bacterial genotype. To investigate the cagA status of H. pylori-infected patients and the relationship between cagA and peptic ulcer disease, gastric biopsy specimens from 103 Caucasian patients in Brazil were analyzed by PCR. Since allelic variation in cagA exists and distinct H. pylori subgenotypes may circulate in different regions, PCR using primers for a variable 3′ region of the cagA gene according to a Japanese methodology and for a consensus cagA 3′ region used in Western methods was used for cagA detection. cagA was present in 53 (71%) of 75 H. pylori-positive cases when analyzed by the consensus region method and was associated with duodenal ulcer disease (P = 0.02), but not with gastric ulcer (P = 0.26), when compared to patients with duodenitis or gastritis. The variable region PCR method was able to detect 43 (57%) cagA-positive cases within the same group of H. pylori-positive patients and showed three subtypes of cagA (A, B/D, and C) that were not associated with clinical outcome. However, in 8 (18%) of the cases, more than one subtype was present, and an association between patients with multiple subtypes and disease outcome was observed when compared to patients with isolated subtypes (P = 0.048). cagA was a marker of H. pylori strains for duodenal ulcer disease in our population, and in spite of the differences in the 3′ region of the cagA gene, the Japanese methodology was able to detect the cagA status in most cases. The presence of multiple subgenotypes of cagA was associated with gastric ulcer. PMID:11158115

  4. Fucosyltransferase-4 and Oligosaccharide Lewis Y Antigen as potentially Correlative Biomarkers of Helicobacter pylori CagA Associated Gastric Cancer.

    PubMed

    Aziz, Faisal; Gao, Wei; Yan, Qiu

    2017-01-01

    H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer but their effect on fucosylation to develop gastric cancer is unknown. Fucosyltransferase IV (FUT4) is the key enzyme for synthesis of LewisY (LeY) carried by glycoproteins and glycolipids on the cell membrane. Herein, we compare the expression of CagA, p-EGFR, FUT4 and LeY in gastritis (n = 128, 176), gastric ulcer (n = 174, 213), and gastric cancer (n = 323, 261) tissue and serum samples, respectively by IHC and ELISA. Moreover, we investigated the potential correlation of CagA with FUT4 and LeY overexpression through EGFR activation. IHC and ELISA results showed higher positive cases of H. pylori CagA (83, 86 %), p-EGFR (81, 72 %), FUT4 (91, 97 %) and LeY (93, 92 %) in gastric cancer, compared to gastritis and gastric ulcer, H. pylori CagA (58, 67 & 59, 73 %), p-EGFR (52, 63 & 35, 47 %), FUT4 (68, 78 & 67, 82 %) and LeY (62,76 & 65, 85 %), respectively. We found a significant high expression (H-Value) of CagA (1.79, 1.66), p-EGFR (1.53, 1.58), FUT4 (2.14, 1.66) and LeY (1.69, 1.61) in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcers, CagA (0.64,1.14), p-EGFR (0.856, 0.678), FUT4 (0.949,1.197) and LeY (0.68,1.008) (P < 0.0001), respectively. Furthermore, H. pylori CagA showed significant correlation with p-EGFR (R-0.62, -0.74), FUT4 (R-0.81, -0.76) and LeY (R-0.82, -0.70) in gastric tissues and serum (P < 0.0001). H. pylori CagA plays key role in the development of gastric cancer with overexpression of FUT4/LeY, serve as potentially correlative biomarkers of H. pylori CagA associated gastric cancer.

  5. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura.

    PubMed

    Takahashi, Toru; Yujiri, Toshiaki; Shinohara, Kenji; Inoue, Yusuke; Sato, Yutaka; Fujii, Yasuhiko; Okubo, Masashi; Zaitsu, Yuzuru; Ariyoshi, Koichi; Nakamura, Yukinori; Nawata, Ryouhei; Oka, Yoshitomo; Shirai, Mutsunori; Tanizawa, Yukio

    2004-01-01

    The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori-positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet-associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori-positive and three H. pylori-negative) patients recognized H. pylori cytotoxin-associated gene A (CagA) protein, and in three completely responsive patients, levels of anti-CagA antibody in platelet eluates declined after eradication therapy. Cross-reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.

  6. Type IV Secretion and Signal Transduction of Helicobacter pylori CagA through Interactions with Host Cell Receptors.

    PubMed

    Backert, Steffen; Tegtmeyer, Nicole

    2017-03-24

    Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA. Numerous T4SS components including CagI, CagL, CagY, and CagA have been shown to target the integrin-β₁ receptor followed by translocation of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine and CagA-containing outer membrane vesicles may also play a role in the delivery process. Translocated CagA undergoes tyrosine phosphorylation in C-terminal EPIYA-repeat motifs by oncogenic Src and Abl kinases. CagA then interacts with an array of host signaling proteins followed by their activation or inactivation in phosphorylation-dependent and phosphorylation-independent fashions. We now count about 25 host cell binding partners of intracellular CagA, which represent the highest quantity of all currently known virulence-associated effector proteins in the microbial world. Here we review the research progress in characterizing interactions of CagA with multiple host cell receptors in the gastric epithelium, including integrin-β₁, EGFR, c-Met, CD44, E-cadherin, and gp130. The contribution of these interactions to H. pylori colonization, signal transduction, and gastric pathogenesis is discussed.

  7. Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study.

    PubMed

    Vaziri, Farzam; Peerayeh, Shahin N; Alebouyeh, Masoud; Maghsoudi, Nader; Azimzadeh, Pedram; Siadat, Seyed D; Zali, Mohammad R

    2015-04-01

    Helicobacter pylori (H. pylori) infection is now recognized as a worldwide problem. Helicobacter pylori CagA is the first bacterial oncoprotein to be identified in relation to human cancer. Helicobacter pylori CagA is noted for structural diversity in its C-terminal region (contains EPIYA motifs), with which CagA interacts with numerous host cell proteins. Deregulation of host signaling by translocated bacterial proteins provides a new aspect of microbial-host cell interaction. The aim of this study is to compare the cellular effects of two different CagA EPIYA motifs on identified signaling pathways involve in gastric carcinogenesis. To investigate the effects of CagA protein carboxyl region variations on the transcription of genes involved in gastric epithelial carcinogenesis pathways, the eukaryotic vector carrying the cagA gene (ABC and ABCCC types) was transfected into gastric cancer cell line. The 42 identified key genes of signal transduction involved in gastric cancer were analyzed at the transcription level by real-time PCR. The results of real-time PCR provide us important clue that the ABCCC oncoprotein variant can change the fate of the cell completely different from ABC type. In fact, these result proposed that the ABCCC type can induce the intestinal metaplasia, IL-8, perturbation of Crk adaptor proteins, anti-apoptotic effect and carcinogenic effect more significantly than ABC type. These data support our hypothesis of a complex interaction of host cell and these two different H. pylori effector variants that determines host cellular fate.

  8. Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.

    PubMed Central

    Crabtree, J E; Covacci, A; Farmery, S M; Xiang, Z; Tompkins, D S; Perry, S; Lindley, I J; Rappuoli, R

    1995-01-01

    AIMS--To use a range of natural phenotypically variant strains of Helicobacter pylori with disparate CagA and VacA (vacuolating cytotoxin) expression to determine which bacterial factors are more closely associated with epithelial interleukin-8 (IL-8) induction. METHODS--Gastric epithelial cells (AGS and KATO-3) were co-cultured with five H pylori strains which were variously shown to express the cagA gene/CagA protein, VacA and/or to exhibit biological cytotoxicity. Secreted IL-8 was assayed by enzyme leaked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) was assayed using a reverse transcription polymerase chain reaction based technique (RT-PCR). RESULTS--Strains expressing CagA, including a variant strain (D931) which is non-cytotoxic and does not express the VacA protein, were found to upregulate epithelial IL-8 secretion and gene expression. In contrast, strains with no CagA expression, even in the presence of VacA and/or biological cytotoxicity, (G104, BA142), failed to induce IL-8 protein or mRNA above control values. CONCLUSIONS--These results strongly support a role for H pylori CagA or coexpressed factors other than the cytotoxin in upregulation of gastric epithelial IL-8. Increased epithelial IL-8 secretion and concomitant neutrophil chemotaxis and activation in addition to direct cytotoxicity may be an important factor in tissue damage and ulceration. Images PMID:7706517

  9. Five-year monitoring of considerable changes in tyrosine phosphorylation motifs of the Helicobacter pylori cagA gene in Iran.

    PubMed

    Kargar, Mohammad; Ghorbani-Dalini, Sadegh; Doosti, Abbas; Najafi, Akram

    2014-08-01

    CagA is a major virulence factor of Helicobacter pylori involved in host cell modulation. The C-terminal part of CagA containing the EPIYA motifs is highly variable and is important for the biological activity of the protein. The aim of this study was consideration of the changes in cagA tyrosine phosphorylation motifs (TPMs) of H. pylori. A set of 302 H. pylori DNA samples from the Iranian population from 2006 to 2011 was selected for the proposed study. The cagA gene and its TPMs were assessed by using polymerase chain reaction (PCR) and specific primers. The prevalence of the cagA gene in our study ranged from 91.43% to 97.06% (with an average of 95.03%). Out of the cagA-positive samples, the prevalence of TPMs A and B increased from 12.5% and 23.44% to 71.2% and 63.63%, respectively. Also, the prevalence of samples infected with Western and East Asian types of H. pylori ranged from 64.06% to 5.73% for the Western type and 17.19% to 51.59% for the East Asian type. Overall, our results showed a high prevalence of the cagA gene. Also, it seems that cagA TPMs of H. pylori is undergoing a change from the Western type to the East Asian type in Iran.

  10. High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

    PubMed Central

    López-Vidal, Yolanda; Ponce-de-León, Sergio; Castillo-Rojas, Gonzalo; Barreto-Zúñiga, Rafael; Torre-Delgadillo, Aldo

    2008-01-01

    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. PMID:19050763

  11. Helicobacter pylori cagA 12-bp insertion can be a marker for duodenal ulcer in Okinawa, Japan

    PubMed Central

    Matsuo, Yuichi; Shiota, Seiji; Matsunari, Osamu; Suzuki, Rumiko; Watada, Masahide; Binh, Tran Thanh; Kinjo, Nagisa; Kinjo, Fukunori; Yamaoka, Yoshio

    2013-01-01

    Backgrounds Helicobacter pylori cagA can be classified into mainly two types (East-Asian-type and Western-type cagA) according to the repeat regions located in the 3′ region. Recent studies showed that the Western-type cagA in strains from Okinawa, Japan formed a different cluster (J-Western-type cagA subtype). We also reported that J-Western-type cagA possess a 12-bp insertion located in the 5′ region of cagA sequence. Methods The prevalence of 12-bp insertion in cagA in Okinawa and the United States (U.S.) was examined by DNA sequencing. We then designed the primer pair which can detect the 12-bp insertion only by polymerase chain reaction (PCR). The prevalence of strains with 12-bp insertion was examined in 336 strains isolated from Okinawa by PCR. Results In case of Western-type cagA/vacA s1m2 strains, the prevalence of 12-bp insertion was significantly higher in strains isolated from Okinawa than that from the U.S. (P = 0.002). Phylogenetic tree showed that strains with 12-bp insertion formed two individual clusters within J-Western-type cagA subtype; one is from Okinawa and another is from the U.S. Our designed primer set showed high sensitivity (100%) and specificity (90.8%) in Okinawa. The 12-bp insertion was found in 23.7%, 14.3%, 4.2%, and 4.0% of strains with duodenal ulcer (DU), gastritis, gastric cancer (GC), and gastric ulcer (GU), respectively (P < 0.001 for DU vs. GU) in Okinawa. Conclusions Although the mechanisms are unknown, the presence of 12-bp insertion was associated with the presence of DU and might have a suppressive action on GU and GC. PMID:23190390

  12. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    SciTech Connect

    Yang, Man; Li, Fu-gang; Xie, Xi-sheng; Wang, Shao-qing; Fan, Jun-ming

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  13. Helicobacter pylori VacA, acting through receptor protein tyrosine phosphatase α, is crucial for CagA phosphorylation in human duodenum carcinoma cell line AZ-521

    PubMed Central

    Yahiro, Kinnosuke; Yamasaki, Eiki; Kurazono, Hisao; Akada, Junko; Yamaoka, Yoshio; Niidome, Takuro; Hatakeyama, Masanori; Suzuki, Hidekazu; Yamamoto, Taro; Moss, Joel; Isomoto, Hajime; Hirayama, Toshiya

    2016-01-01

    ABSTRACT Helicobacter pylori, a major cause of gastroduodenal diseases, produces vacuolating cytotoxin (VacA) and cytotoxin-associated gene A (CagA), which seem to be involved in virulence. VacA exhibits pleiotropic actions in gastroduodenal disorders via its specific receptors. Recently, we found that VacA induced the phosphorylation of cellular Src kinase (Src) at Tyr418 in AZ-521 cells. Silencing of receptor protein tyrosine phosphatase (RPTP)α, a VacA receptor, reduced VacA-induced Src phosphorylation. Src is responsible for tyrosine phosphorylation of CagA at its Glu-Pro-Ile-Tyr-Ala (EPIYA) variant C (EPIYA-C) motif in Helicobacter pylori-infected gastric epithelial cells, resulting in binding of CagA to SHP-2 phosphatase. Challenging AZ-521 cells with wild-type H. pylori induced phosphorylation of CagA, but this did not occur when challenged with a vacA gene-disrupted mutant strain. CagA phosphorylation was observed in cells infected with a vacA gene-disrupted mutant strain after addition of purified VacA, suggesting that VacA is required for H. pylori-induced CagA phosphorylation. Following siRNA-mediated RPTPα knockdown in AZ-521 cells, infection with wild-type H. pylori and treatment with VacA did not induce CagA phosphorylation. Taken together, these results support our conclusion that VacA mediates CagA phosphorylation through RPTPα in AZ-521 cells. These data indicate the possibility that Src phosphorylation induced by VacA is mediated through RPTPα, resulting in activation of Src, leading to CagA phosphorylation at Tyr972 in AZ-521 cells. PMID:27935824

  14. Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation

    PubMed Central

    Wang, Ge; Romero-Gallo, Judith; Benoit, Stéphane L.; Piazuelo, M. Blanca; Dominguez, Ricardo L.; Morgan, Douglas R.; Peek, Richard M.

    2016-01-01

    ABSTRACT A known virulence factor of Helicobacter pylori that augments gastric cancer risk is the CagA cytotoxin. A carcinogenic derivative strain, 7.13, that has a greater ability to translocate CagA exhibits much higher hydrogenase activity than its parent noncarcinogenic strain, B128. A Δhyd mutant strain with deletion of hydrogenase genes was ineffective in CagA translocation into human gastric epithelial AGS cells, while no significant attenuation of cell adhesion was observed. The quinone reductase inhibitor 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO) was used to specifically inhibit the H2-utilizing respiratory chain of outer membrane-permeabilized bacterial cells; that level of inhibitor also greatly attenuated CagA translocation into AGS cells, indicating the H2-generated transmembrane potential is a contributor to toxin translocation. The Δhyd strain showed a decreased frequency of DNA transformation, suggesting that H. pylori hydrogenase is also involved in energizing the DNA uptake apparatus. In a gerbil model of infection, the ability of the Δhyd strain to induce inflammation was significantly attenuated (at 12 weeks postinoculation), while all of the gerbils infected with the parent strain (7.13) exhibited a high level of inflammation. Gastric cancer developed in 50% of gerbils infected with the wild-type strain 7.13 but in none of the animals infected with the Δhyd strain. By examining the hydrogenase activities from well-defined clinical H. pylori isolates, we observed that strains isolated from cancer patients (n = 6) have a significantly higher hydrogenase (H2/O2) activity than the strains isolated from gastritis patients (n = 6), further supporting an association between H. pylori hydrogenase activity and gastric carcinogenesis in humans. PMID:27531909

  15. Helicobacter pylori CagA and IL-1β Promote the Epithelial-to-Mesenchymal Transition in a Nontransformed Epithelial Cell Model

    PubMed Central

    Arévalo-Romero, Haruki; Meza, Isaura; Vallejo-Flores, Gabriela

    2016-01-01

    Gastric cancer is the third cause of cancer death worldwide and infection by Helicobacter pylori (H. pylori) is considered the most important risk factor, mainly by the activity of its virulence factor CagA. H. pylori/CagA-induced chronic inflammation triggers a series of gastric lesions of increased severity, starting with gastritis and ending with cancer. IL-1β has been associated with tumor development and invasiveness in different types of cancer, including gastric cancer. Currently, it is not clear if there is an association between CagA and IL-1β at a cellular level. In this study, we analyzed the effects of IL-1β and CagA on MCF-10A nontransformed cells. We found evidence that both CagA and IL-1β trigger the initiation of the epithelial-to-mesenchymal transition characterized by β-catenin nuclear translocation, increased expression of Snail1 and ZEB1, downregulation of CDH1, and morphological changes during MCF-10A acini formation. However, only CagA induced MMP9 activity and cell invasion. Our data support that IL-1β and CagA target the β-catenin pathway, with CagA leading to acquisition of a stage related to aggressive tumors. PMID:27525003

  16. Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

    PubMed Central

    Vallejo-Flores, Gabriela; Torres, Javier; Sandoval-Montes, Claudia; Arévalo-Romero, Haruki; Meza, Isaura; Camorlinga-Ponce, Margarita; Torres-Morales, Julián; Chávez-Rueda, Adriana Karina; Legorreta-Haquet, María Victoria; Fuentes-Pananá, Ezequiel M.

    2015-01-01

    H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion. PMID:26557697

  17. Proteomic Characterization of Helicobacter pylori CagA Antigen Recognized by Child Serum Antibodies and Its Epitope Mapping by Peptide Array

    PubMed Central

    Akada, Junko; Okuda, Masumi; Hiramoto, Narumi; Kitagawa, Takao; Zhang, Xiulian; Kamei, Shuichi; Ito, Akane; Nakamura, Mikiko; Uchida, Tomohisa; Hiwatani, Tomoko; Fukuda, Yoshihiro; Nakazawa, Teruko; Kuramitsu, Yasuhiro; Nakamura, Kazuyuki

    2014-01-01

    Serum antibodies against pathogenic bacteria play immunologically protective roles, and can be utilized as diagnostic markers of infection. This study focused on Japanese child serum antibodies against Helicobacter pylori, a chronically-infected gastric bacterium which causes gastric cancer in adults. Serological diagnosis for H. pylori infection is well established for adults, but it needs to be improved for children. Serum samples from 24 children, 22 H. pylori (Hp)-positive and 2 Hp-negative children, were used to catalogue antigenic proteins of a Japanese strain CPY2052 by two-dimensional electrophoresis followed by immunoblot and LC-MS/MS analysis. In total, 24 proteins were identified as candidate antigen proteins. Among these, the major virulence factor, cytotoxin-associated gene A protein (CagA) was the most reactive antigen recognized by all the Hp-positive sera even from children under the age of 3 years. The major antigenic part of CagA was identified in the middle region, and two peptides containing CagA epitopes were identified using a newly developed peptide/protein-combined array chip method, modified from our previous protein chip method. Each of the epitopes was found to contain amino acid residue(s) unique to East Asian CagA. Epitope analysis of CagA indicated importance of the regional CagA antigens for serodiagnosis of H. pylori infection in children. PMID:25141238

  18. CagA and VacA Polymorphisms Do Not Correlate with Severity of Histopathological Lesions in Helicobacter pylori-Infected Greek Children▿ †

    PubMed Central

    Sgouras, Dionyssios N.; Panayotopoulou, Effrosini G.; Papadakos, Konstantinos; Martinez-Gonzalez, Beatriz; Roumbani, Aikaterini; Panayiotou, Joanna; vanVliet-Constantinidou, Cathy; Mentis, Andreas F.; Roma-Giannikou, Eleftheria

    2009-01-01

    The presence of various numbers of EPIYA tyrosine phosphorylation motifs in the CagA protein of Helicobacter pylori has been suggested to contribute to pathogenesis in adults. In this prospective study, we characterized H. pylori isolates from symptomatic children, with reference to the diversity of functional EPIYA motifs in the CagA protein and vacA isotypes, and assessed the potential correlation with the histopathological manifestations of the infection. We analyzed 105 H. pylori isolates from 98 children and determined the diversity of EPIYA motifs in CagA by amplification and sequencing of the 3′ variable region of the cagA gene as well as vacA isotypes for the signal, middle, and intermediate regions. CagA phosphorylation and levels of secreted IL-8 were determined following in vitro infection of AGS gastric epithelial cells. Histopathological evaluation of H. pylori colonization, activity, and severity of the associated gastritis was performed according to the updated Sydney criteria. EPIYA A (GLKN[ST]EPIYAKVNKKK), EPIYA B (Q[V/A]ASPEPIY[A/T]QVAKKVNAKI), and EPIYA C (RS[V/A]SPEPIYATIDDLG) motifs were detected in the ABC (46.6%) and ABCC (17.1%) combinations. No isolates harboring more than two EPIYA C motifs in CagA were found. The presence of isogenic strains with variable numbers of CagA EPIYA C motifs within the same patient was detected in seven cases. Occurrence of increasing numbers of EPIYA C motifs correlated strongly with presence of a high-vacuolation (s1 or s2/i1/m1) phenotype and age. A weak positive correlation was observed between vacuolating vacA genotypes and presence of nodular gastritis. However, CagA- and VacA-dependent pathogenicities were not found to contribute to severity of histopathology manifestations in H. pylori-infected children. PMID:19535517

  19. CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer

    PubMed Central

    Srivastava, Supriya; Samanta, Animesh; Sharma, Neel; Tan, Kar Tong; Yang, Henry; Voon, Dominic C.; Pang, Brendan; Teh, Ming; Murata-Kamiya, Naoko; Hatakeyama, Masanori; Chang, Young-Tae; Yong, Wei Peng; Ito, Yoshiaki; Ho, Khek Yu; Tan, Patrick; Soong, Richie; Koeffler, Phillip H.; Yeoh, Khay Guan; Jeyasekharan, Anand D.

    2016-01-01

    Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach. PMID:27421133

  20. Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion.

    PubMed

    Argent, Richard H; Hale, James L; El-Omar, Emad M; Atherton, John C

    2008-09-01

    Helicobacter pylori strains from East Asia have an 'East Asian' type of CagA that is more active and predominantly comprises a single type. Strains from other countries have a 'western' type of CagA, which is less active and comprises many different types generated by intragenomic recombination. Co-culture of AGS gastric epithelial cells with isolates of western strains that displayed microevolution in CagA showed that isolates with additional copies of the C motif induced significantly more interleukin (IL)-8 secretion. Co-culture of AGS cells with western and East Asian strains, each expressing CagA with a single copy of the C or D motif, showed that East Asian strains induced significantly more IL-8 secretion. Analysis of the different CagA types from data deposited in GenBank and from the literature showed that western CagA is significantly more likely to undergo duplication of tyrosine phosphorylation motif C than East Asian CagA is of the corresponding D motif. Taken together, the data suggest that the already highly active East Asian CagA with one D motif has no requirement to increase its virulence, whereas the less active western CagA displays flexibility in its capacity to increase its number of tyrosine phosphorylation motifs to become more virulent.

  1. Presumptive mechanisms of peptic ulceration by Helicobacter pylori VacA involving mucoprotease and CagA.

    PubMed

    Choi, K M; Lim, W J; Park, J K; Hwang, S Y

    2001-06-30

    Helicobacter pylori vacuolating toxin (VacA) appears to be unusually stable, not only against extreme pH conditions or high temperatures, but also against common organic solvents or detergents. Under acidic conditions, its activity was markedly increased in the manner of temperature-independent, suggesting a spontaneous activation. A similar finding was also observed under alkaline conditions, however, it should have an appropriate temperature. From these observations, the mechanisms of VacA activation were suggested to be so redundant that either the case of acidic or basic amino acid residues could be involved in the VacA activation. Separately, we also found that the VacA production by H. pylori was pH-dependent: Its production was increased at a low pH region with a broad range (1.0-5.0), and at a high pH region with a narrow range (8.0-9.0). Astonishingly, a highly immunogenic CagA did not appear to be expressed under the acidic conditions. Its expression, however, was shown to be enhanced when the surrounding pH of this bacterium was raised. In contrast, mucoproteolytic activity in the H. pylori membrane was found to be increased at acidic conditions. Considering these observations, together with the stomach and duodenal pH of humans, two presumptive mechanisms of H. pylori VacA-associated ulceration may be deduced; namely, an acid- and an alkali-dependent type, involving mucoprotease and CagA, respectively.

  2. Effect of treatment failure on the CagA EPIYA motif in Helicobacter pylori strains from Colombian subjects

    PubMed Central

    Bustamante-Rengifo, Javier Andres; Matta, Andres Jenuer; Pazos, Alvaro Jairo; Bravo, Luis Eduardo

    2017-01-01

    AIM To evaluate effect of treatment failure on cagA and vacA genotypes in Helicobacter pylori (H. pylori) isolates from Colombia. METHODS One hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cagA and vacA genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA (RAPD) fingerprinting. RESULTS Treatment effectiveness was at 74.6%. Of the participants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of post-treatment infection was 64% (16/25) and 40% (10/25) by histology and culture, respectively. Upon comparing the cagA and vacA genotypes found before and after therapy, multiple cagA genotypes (cagA-positive and cagA-negative) were found before treatment; in contrast, cagA-negative genotypes decreased after treatment. vacA s1m1 genotype was highly prevalent in patients before and after therapy. The 3’cagA region was successfully amplified in 95.5% (21/22) of the isolates obtained before and in 81.8% (18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7% (16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment. CONCLUSION Unsuccessful treatment limits colonization by low-virulence strains resulting in partial and selective eradication in mixed infections, and acts on the cagA-positive strains inducing genetic rearrangements in cagA variable region that produces a loss or gain of EPIYA repetitions. PMID:28373764

  3. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions.

    PubMed

    Zhang, Xue-Song; Tegtmeyer, Nicole; Traube, Leah; Jindal, Shawn; Perez-Perez, Guillermo; Sticht, Heinrich; Backert, Steffen; Blaser, Martin J

    2015-02-01

    Helicobacter pylori persistently colonizes the human stomach, with mixed roles in human health. The CagA protein, a key host-interaction factor, is translocated by a type IV secretion system into host epithelial cells, where its EPIYA tyrosine phosphorylation motifs (TPMs) are recognized by host cell kinases, leading to multiple host cell signaling cascades. The CagA TPMs have been described as type A, B, C or D, each with a specific conserved amino acid sequence surrounding EPIYA. Database searching revealed strong non-random distribution of the B-motifs (including EPIYA and EPIYT) in Western H. pylori isolates. In silico analysis of Western H. pylori CagA sequences provided evidence that the EPIYT B-TPMs are significantly less associated with gastric cancer than the EPIYA B-TPMs. By generating and using a phosphorylated CagA B-TPM-specific antibody, we demonstrated the phosphorylated state of the CagA B-TPM EPIYT during H. pylori co-culture with host cells. We also showed that within host cells, CagA interaction with phosphoinositol 3-kinase (PI3-kinase) was B-TPM tyrosine-phosphorylation-dependent, and the recombinant CagA with EPIYT B-TPM had higher affinity to PI3-kinase and enhanced induction of AKT than the isogenic CagA with EPIYA B-TPM. Structural modeling of the CagA B-TPM motif bound to PI3-kinase indicated that the threonine residue at the pY+1 position forms a side-chain hydrogen bond to N-417 of PI3-kinase, which cannot be formed by alanine. During co-culture with AGS cells, an H. pylori strain with a CagA EPIYT B-TPM had significantly attenuated induction of interleukin-8 and hummingbird phenotype, compared to the isogenic strain with B-TPM EPIYA. These results suggest that the A/T polymorphisms could regulate CagA activity through interfering with host signaling pathways related to carcinogenesis, thus influencing cancer risk.

  4. Association among H. pylori virulence markers dupA, cagA and vacA in Brazilian patients

    PubMed Central

    2014-01-01

    Background Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pylori appear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor of Helicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence of dupA gene and evaluate the association among dupA and other virulence factors including cagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method. Results Patients with gastritis tested positive for H. pylori more frequently. The dupA gene was detected in 41.5% of them (85/205); cagA gene was found in 98 isolates (47.8%) and vacA genotype s1/m1 in 50.2%, s1/m2 in 8.3%, s2/m2 in 36.6%, s2/m1 in 0.5% and s1/s2/m1/m2 in 4.4%. We also verified a significant association between cagA and dupA genes [p = 0.0003, relative risk (RR) 1.73 and confidence interval [CI] = 1.3–2.3]. The genotypes s1/m1 were also associated with dupA gene (p = 0.0001, RR: 1.72 and CI: 1.3–2.2). The same associations were found when analyzing pediatric and adult groups of patients individually. Conclusion Ours results suggest that dupA is highly frequent in Brazilian patients and is associated with cagA gene and vacA s1/m1 genotype, and it may be considered an important virulence factor in the development of gastric diseases in adults or children. PMID:24456629

  5. Activation of Helicobacter pylori CagA by tyrosine phosphorylation is essential for dephosphorylation of host cell proteins in gastric epithelial cells.

    PubMed

    Püls, Jurgen; Fischer, Wolfgang; Haas, Rainer

    2002-02-01

    Helicobacter pylori type I strains harbour the cag pathogenicity island (cag-PAI), a 37 kb sequence,which encodes the components of a type IV secretion system. CagA, the first identified effector protein of the cag-PAI, is translocated into eukaryotic cells and tyrosine phosphorylated (CagAP-tyr) by a host cell tyrosine kinase. Translocation of CagA induces the dephosphorylation of a set of phosphorylated host cell proteins of unknown identity. CagA proteins of independent H. pylori strains vary in sequence and thus in the number and composition of putative tyrosine phosphorylation motifs (TPMs). The CagA protein of H. pylori strain J99 (CagAJ99) does not carry any of three putative tyrosine phosphorylation motifs (TPM-A, TPM-B or TPM-C) predicted by the MOTIF algorithm in CagA proteins. CagA,n is not tyrosine phosphorylated and is inactive in the dephosphorylation of host cell proteins. By site-specific mutagenesis,we introduced a TPM-C into CagA,. by replacing a single lysine with a tyrosine. This slight modification resulted in tyrosine phosphorylation of CagAJ99 and host cell protein dephosphorylation. In contrast, the removal of the indigenous TPM-C from CagAP12 did not abolish its tyrosine phosphorylation, suggesting that further phosphorylated sites are present in CagAP12. By generation of hybrid CagA proteins, a phosphorylation of the most N-terminal TPM-A could be excluded. Our data suggest that tyrosine phosphorylation at TPM-C is sufficient, but not exclusive,to activate translocated CagA. Activated CagAPtr might either convert into a phosphatase itself or activate a cellular phosphatase to dephosphorylate cellular phosphoproteins and modulate cellular signalling cascades of the host.

  6. Characterization of virulence genes cagA and vacA in Helicobacter Pylori and their prevalence in gastrointestinal disorders

    PubMed Central

    Cogo, Laura Lúcia; Monteiro, Cristina Leise Bastos; Nogueira, Keite da Silva; Palmeiro, Jussara Kasuko; Ribeiro, Marcelo Lima; de Camargo, Eloá Ramalho; Neves, Daniel Locatelli; do Nascimento, Aguinaldo José; Costa, Libera Maria Dalla

    2011-01-01

    Prevalence of H. pylori infection was determined using cultures of gastric biopsy samples of patients attended at the academic hospital of the Federal University of Paraná, Curitiba, Paraná, Brazil. Molecular methods were used to characterize the cagA and vacA genes from bacterial isolates associated with different diseases presented by patients. Out of a total of 81, forty-two gastric biopsy samples tested were positive for H. pylori, with a prevalence of 51.9%. No significant difference was found with regard to the gender (p=0.793) and age (p=0.183) of the patients. Genotype s1m1 vacA gene was found in 67% of the cases of peptic ulcer investigated (p=1.0), despite the limited number of patients with this disease (n=3). A correlation between the presence of less virulent strains (s2m2) and reflux esophagitis was found in the majority of the cases (45%), but without statistical significance. An association between the prevalence of cagA gene, found in 92% of isolates, and peptic ulcer was not observed (p=1.0), suggesting that this gene cannot be considered a specific marker of severity in our environment. The results reinforce the importance of conducting regional studies and the need to characterize H. pylori virulence genes associated with different diseases. PMID:24031754

  7. Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk

    PubMed Central

    Chaturvedi, Rupesh; de Sablet, Thibaut; Peek, Richard M.; Wilson, Keith T.

    2012-01-01

    We have recently reported that Helicobacter pylori strains expressing the virulence factor cytotoxin-associated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA– strains did not. SMO catabolizes the polyamine spermine and produces H2O2 that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA+, but not cagA– strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMOhigh gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation. PMID:22555547

  8. MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells.

    PubMed

    Zhu, Yongliang; Jiang, Qiaoli; Lou, Xiaojun; Ji, Xiaowei; Wen, Zhenzhen; Wu, Jia; Tao, Haiying; Jiang, Tingting; He, Wei; Wang, Caihua; Du, Qin; Zheng, Shu; Mao, Jianshan; Huang, Jian

    2012-01-01

    CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA.

  9. Prevalence of cagA and vacA among Helicobacter pylori-infected patients in Iran: a systematic review and meta-analysis.

    PubMed

    Sayehmiri, Fatemeh; Kiani, Faezeh; Sayehmiri, Kourosh; Soroush, Setareh; Asadollahi, Khairollah; Alikhani, Mohammad Yousef; Delpisheh, Ali; Emaneini, Mohammad; Bogdanović, Lidija; Varzi, Ali Mohammad; Zarrilli, Raffaele; Taherikalani, Morovat

    2015-07-30

    The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and host-related factors. This study aimed to investigate the prevalence of cagA and vacA genes among H. pylori-infected patients in Iran and analyze their relevance to the disease status between two clinical groups via a meta-analysis method. Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were investigated, and 23 relevant articles from the period between 2001 and 2012 were finally analyzed. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R software and STATA. The prevalence of cagA and vacA genes among H. pylori-infected patients was 70% (95% CI, 64-75) and 41% (95% CI, 24.3-57.7), respectively. The prevalence of duodenal ulcers, peptic ulcers, and gastritis among cagA+ individuals was 53% (95% CI, 20-86), 65% (95% CI, 34-97), and 71% (95% CI, 59-84), respectively. Odds ratio (OR) between cagA-positive compared with cagA-negative patients showed a 1.89 (95% CI, 1.38-2.57) risk of ulcers. In conclusion, the frequency of cagA gene among H. pylori strains is elevated in Iran and it seems to be more frequently associated with gastritis. Therefore, any information about cagA and vacA prevalence among different H. pylori-infected clinical groups in the country can help public health authorities to plan preventive policies to reduce the prevalence of diseases associated with H. pylori infection.

  10. Interaction with CagF Is Required for Translocation of CagA into the Host via the Helicobacter pylori Type IV Secretion System

    PubMed Central

    Couturier, Marc Roger; Tasca, Elizabetta; Montecucco, Cesare; Stein, Markus

    2006-01-01

    Development of severe gastric diseases is strongly associated with those strains of Helicobacter pylori that contain the cag pathogenicity island (PAI) inserted into the chromosome. The cag PAI encodes a type IV secretion system that translocates the major disease-associated virulence protein, CagA, into the host epithelial cell. CagA then affects host signaling pathways, leading to cell elongations and inflammation. Since the precise mechanism by which the CagA toxin is translocated by the type IV secretion system remained elusive, we used fusion proteins and immunoprecipitation studies to identify CagA-interacting secretion components. Here we demonstrate that CagA, in addition to other yet-unidentified proteins, interacts with CagF, presumably at the inner bacterial membrane. This interaction is required for CagA translocation, since an isogenic nonpolar cagF mutant was translocation deficient. Our results suggest that CagF may be a protein with unique chaperone-like function that is involved in the early steps of CagA recognition and delivery into the type IV secretion channel. PMID:16368981

  11. Different distribution of Helicobacter pylori EPIYA- cagA motifs and dupA genes in the upper gastrointestinal diseases and correlation with clinical outcomes in iranian patients

    PubMed Central

    Haddadi, Mohammad Hossein; Bazargani, Abdollah; Khashei, Reza; Fattahi, Mohammad Reza; Bagheri Lankarani, Kamran; Moini, Maryam; Rokni Hosseini, Seyed Mohammad Hossein

    2015-01-01

    Aim: Our aim was to determine the EPIYA-cagA Phosphorylation sites and dupA gene in H. pylori isolates among patients with upper gastrointestinal diseases. Background: Pathogenicity of the cagA-positive Helicobacter pylori is associated with EPIYA motifs and higher number of EPIYA-C segments is a risk factor of gastric cancer, while duodenal ulcer-promoting gene (dupA) is determined as a protective factor against gastric cancer. Patients and methods: A total of 280 non-repeated gastric biopsies obtained from patients undergoing endoscopy from January 2013 till July 2013. Samples were cultured on selective horse blood agar and incubated in microaerophilic atmosphere. The isolated organisms were identified as H. pylori by Gram staining and positive oxidase, catalase, and urease tests. Various motif types of cagA and the prevalence of dupA were determined by PCR method. Results: Out of 280 specimens, 128 (54.7%) isolated organisms were identified as H. pylori. Of 120 H. pylori isolates, 35.9% were dupA positive and 56.26% were cagA positive, while cagA with ABC and ABCC motifs were 55.5% and 44.5%, respectively. Fifty six percent of the isolates with the ABCC motif have had dupA genes. We also found a significant association between strains with genotypes of dupA-ABC and duodenal ulcer disease (p = 0.007). Conclusion: The results of this study showed that the prevalence of cagA-positive H. pylori in Shiraz was as high as in western countries and higher numbers of EPIYA-C segments were seen in gastric cancer patients. We may also use dupA as a prognostic and pathogenic marker for duodenal ulcer disease and cagA with the segment C for gastric cancer and gastric ulcer disease in this region. PMID:26171136

  12. The Role of H. pylori CagA in Regulating Hormones of Functional Dyspepsia Patients

    PubMed Central

    Meng, Wang-Ping; Wang, Zhong-Qiong; Deng, Jia-Qi; Liu, Yi

    2016-01-01

    Helicobacter pylori (H. pylori, Hp) colonizes the stomachs of approximately 20%–80% of humans throughout the world. The Word Healthy Organization (WHO) classified H. pylori as a group 1 carcinogenic factor in 1994. Recently, an increasing number of studies has shown an association between H. pylori infection and various extragastric diseases. Functional dyspepsia (FD) is considered a biopsychosocial disorder with multifactorial pathogenesis, and studies have shown that infection with CagA-positive H. pylori strains could explain some of the symptoms of functional dyspepsia. Moreover, CagA-positive H. pylori strains have been shown to affect the secretion of several hormones, including 5-HT, ghrelin, dopamine, and gastrin, and altered levels of these hormones might be the cause of the psychological disorders of functional dyspepsia patients. This review describes the mutual effects of H. pylori and hormones in functional dyspepsia and provides new insight into the pathogenesis of functional dyspepsia. PMID:27840636

  13. Risk of advanced gastric precancerous lesions in Helicobacter pylori infected subjects is influenced by ABO blood group and cagA status.

    PubMed

    Rizzato, Cosmeri; Kato, Ikuko; Plummer, Martyn; Muñoz, Nubia; Stein, Angelika; Jan van Doorn, Leen; Franceschi, Silvia; Canzian, Federico

    2013-07-15

    A higher incidence of stomach cancer in ABO blood type A individuals than in those with blood type O has been known for a long time. We studied this association in relation to Helicobacter pylori (Hp) of different cagA status. For our study, we used baseline gastric histopathology data and DNAs from frozen gastric biopsies of 2,077 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela. We analyzed six single nucleotide polymorphisms in the ABO gene, and we assessed the presence of the Hp cagA gene. Odds ratios (ORs) for risk of advanced precancerous gastric lesions were calculated using individuals with normal gastric epithelium or non-atrophic gastritis as a reference. Among individuals carrying a cagA negative Hp infection or no Hp infection, those with blood type A had a lower risk of intestinal metaplasia (IM) and dysplasia than those with blood type O (OR=0.60; 95% CI 0.38-0.94). In carriers of cagA positive Hp strains, individuals with blood type A had a higher risk of IM or dysplasia than those with blood type O (OR=1.42, 95% CI 1.09-1.86) and a higher risk if compared to subjects carrying cagA negative strain and non-A blood group (OR=3.82, 95% CI=2.80-5.20). The interaction between Hp cagA status and blood type was statistically significant (p=0.0006). We showed that SNPs in the ABO gene, predictive of ABO blood groups, are associated with risk of advanced precancerous gastric lesions in individuals infected with Hp, but the assessment of the risk is strictly dependent on cagA status.

  14. Simple method for determination of the number of Helicobacter pylori CagA variable-region EPIYA tyrosine phosphorylation motifs by PCR.

    PubMed

    Argent, Richard H; Zhang, Youli; Atherton, John C

    2005-02-01

    Helicobacter pylori strains possessing the cag pathogenicity island are associated with the development of gastric cancer. The CagA protein is translocated into epithelial cells and becomes phosphorylated on tyrosine residues within EPIYA motifs, which may be repeated within the variable region of the protein. Strains possessing CagA with greater numbers of these repeats have been more closely associated with gastric carcinogenesis. Phosphorylated CagA leads to epithelial cell elongation, which is dependent on the number of variable-region EPIYA motifs. Thus, determination of the degree of CagA phosphorylation and the number of EPIYA motifs appears to be more important than detection of cagA alone. Determination of the number of EPIYA motifs by nucleotide sequencing, however, is a laborious and expensive process. We describe here a novel and rapid PCR method for determination of the pattern of repeats containing the EPIYA motif. This will aid in the identification of those strains that may be more likely to cause disease.

  15. Total leukocyte counts and neutrophil-lymphocyte count ratios among Helicobacter pylori-infected patients with peptic ulcers: independent of bacterial CagA status.

    PubMed

    Jafarzadeh, A; Akbarpoor, V; Nabizadeh, M; Nemati, M; Rezayati, M T

    2013-01-01

    Elevated leukocyte counts can be a marker of inflammation and infection. The aim of this study was to determine the total leukocyte count and neutrophil-lymphocyte count ratio (NLCR) among Helicobacter pylori-infected patients with peptic ulcer disease (PU) and among asymptomatic subjects (AS) and to evaluate if there is an association between these lab values and the presence of the H. pylori virulence factor cytotoxin-associated gene A (CagA). Sixty H. pylori-infected PU patients, 63 AS carriers and 32 healthy H. pylori-negative subjects (controls) were included in the study. The total white blood cell (WBC) counts and differentials were determined using standard hematological methods. The mean total WBC count, mean neutrophil count and NLCR were significantly higher among PU patients than in controls (p < 0.001, p < 0.001 and p < 0.001, respectively). Similarly, the mean WBC count, mean neutrophil count and NLCR were significantly higher among AS patients than in controls (p < 0.005, p < 0.001 and p < 0.02, respectively). The differences of mean WBC counts mean neutrophil counts and NLCR were also significantly different (p < 0.005, p < 0.001 and p < 0.001, respectively) between the PU and AS patients. There were no differences in the PU and AS patients in regard to anti-CagA positivity. These results show the CagA factor was not associated with the presence or absence of symptoms in H. pylori infected patients.

  16. Risk of advanced gastric precancerous lesions in Helicobacter pylori infected subjects is influenced by ABO blood group and cagA status

    PubMed Central

    Rizzato, Cosmeri; Kato, Ikuko; Plummer, Martyn; Muñoz, Nubia; Stein, Angelika; van Doorn, Leen Jan; Franceschi, Silvia; Canzian, Federico

    2013-01-01

    A higher incidence of stomach cancer in ABO blood type A individuals than in those with blood type O has been known for a long time. We studied this association in relation to Helicobacter pylori (Hp) of different cagA status. For this study we used baseline gastric histopathology data and DNAs from frozen gastric biopsies of 2077 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela. We analyzed 6 single nucleotide polymorphisms in the ABO gene and we assessed the presence of the Hp cagA gene. Odds ratios for risk of advanced precancerous gastric lesions were calculated using individuals with normal gastric epithelium or non-atrophic gastritis as a reference. Among individuals carrying a cagA negative Hp infection or no Hp infection, those with blood type A had a lower risk of intestinal metaplasia and dysplasia than those with blood type O (OR=0.60; 95% CI 0.38-0.94). In carriers of cagA positive Hp strains, individuals with blood type A had a higher risk of intestinal metaplasia or dysplasia than those with blood type O (OR=1.42, 95% CI 1.09-1.86) and a higher risk if compared with subjects carrying cagA− strain and non-A blood group (OR=3.82, 95%CI=2.80-5.20). The interaction between Hp cagA status and blood type was statistically significant (P=0.0006). We showed that SNPs in the ABO gene, predictive of ABO blood groups, are associated with risk of advanced precancerous gastric lesions in individuals infected with Hp, but the assessment of the risk is strictly dependent on cagA status. PMID:23319424

  17. Helicobacter pylori CagL Y58/E59 Mutation Turns-Off Type IV Secretion-Dependent Delivery of CagA into Host Cells

    PubMed Central

    Tegtmeyer, Nicole; Lind, Judith; Schmid, Benedikt; Backert, Steffen

    2014-01-01

    The type IV secretion system (T4SS) is a major virulence determinant of the gastric pathogen Helicobacter pylori. The CagL protein is a specialized adhesin of the corresponding T4SS pilus, which establishes initial contact with the integrin β1 receptor on host target cells. Recent studies proposed that Y58 and E59 amino acid polymorphisms in CagL increase the virulence of H. pylori strains by enhanced translocation and phosphorylation of the CagA effector protein. These polymorphisms were therefore correlated with an increased risk of gastric cancer development. Here we show that the Y58/E59 motif, which is located in a loop connecting two α-helices, and corresponding polymorphisms could influence the function of CagL. However, expression of isogenic CagL Y58/E59 variants in H. pylori strain 26695 significantly blocked the translocation and phosphorylation of CagA as compared to complemented wild-type CagL. These results suggest that the function of the T4SS for delivery of CagA is turned-off by the Y58/E59 mutation in CagL. This activity appears to be similar to the one recently described for another T4SS pilus protein, CagY, which is also sufficient to cause gain or loss of T4SS function. These data support the hypothesis that certain mutations in CagL or recombination events in CagY may serve as a sort of molecular switch or perhaps rheostat in the T4SS, which could alter the function of the pilus and "tunes" injection of CagA and host pro-inflammatory responses, respectively. PMID:24893039

  18. Association between cagA, vacAi, and dupA genes of Helicobacter pylori and gastroduodenal pathologies in Chilean patients.

    PubMed

    Paredes-Osses, Esteban; Sáez, Katia; Sanhueza, Enrique; Hebel, Sonja; González, Carlos; Briceño, Carlos; García Cancino, Apolinaria

    2017-03-11

    In addition to the already known cagA gene, novel genetic markers have been associated with Helicobacter pylori (H. pylori) virulence: the dupA and vacAi genes. These genes might play an important role as specific markers to determine the clinical outcome of the disease, especially the vacAi gene, which has been expected to be a good marker of severe pathologies like gastric adenocarcinoma. In the present study, the association of cagA, dupA, and vacAi genes with gastroduodenal pathologies in Chilean patients was studied. One hundred and thirty-two patients positive for H. pylori were divided into two groups-non-severe and severe gastric pathologies-and investigated for the presence of cagA, dupA, and vacAi H. pylori virulence genes by PCR. The cagA gene was detected in 20/132 patients (15.2%), the vacAi1 gene was detected in 54/132 patients (40.9%), the vacAi2 gene was detected in 26/132 patients (19.7%), and the dupA gene was detected in 50/132 (37.9%) patients. Logistic regression model analysis showed that the vacAi1 isoform gene in the infected strains and the severity of the diseases outcome were highly associated, causing severe gastric damage that may lead to gastric cancer (p < 0.0001; OR = 8.75; 95% CI 3.54-21.64). Conversely, cagA (p = 0.3507; OR = 1.62; 95% CI 0.59-4.45) and vacAi2 (p = 0.0114; OR = 3.09; 95% CI 1.26-7.60) genes were not associated with damage, while the dupA gene was associated significantly with non-severe clinical outcome (p = 0.0032; OR = 0.25; 95% CI 0.09-0.65). In addition, dupA gene exerts protection against severe gastric pathologies induced by vacAi1 by delaying the outcome of the disease by approximately 20 years.

  19. [Helicobacter pylori: focus on CagA and VacA major virulence factors].

    PubMed

    Castillo-Rojas, Gonzalo; Mazarí-Hiriart, Marisa; López-Vidal, Yolanda

    2004-01-01

    After colonizing the human gastric mucosa, Helicobacter pylori can remain within the host for years and even decades, and is associated with several, highly significant gastric pathologies. In Mexico, the seroprevalence at 1 year of age is 20% and the estimated increment in seropositivity per year is 5% for children aged 1-10 years. More than 80% of adults are infected by the time they are 18-20 years old. Bacterial virulence factors have been proposed for H. pylori, such as urease, flagella, heat-shock protein, lipopolysaccharide, adhesions, vacuolating cytotoxin, cag pathogenicity island and the cytotoxin-associated protein, the latter being the most studied mechanism to date.

  20. Capsaicin consumption, Helicobacter pylori CagA status and IL1B-31C>T genotypes: a host and environment interaction in gastric cancer.

    PubMed

    López-Carrillo, Lizbeth; Camargo, M Constanza; Schneider, Barbara G; Sicinschi, Liviu A; Hernández-Ramírez, Raúl U; Correa, Pelayo; Cebrian, Mariano E

    2012-06-01

    Gastric cancer (GC) has been associated with a complex combination of genetic and environmental factors. In contrast to most countries, available information on GC mortality trends showed a gradual increase in Mexico. Our aim was to explore potential interactions among dietary (chili pepper consumption), infectious (Helicobacter pylori) and genetic factors (IL1B-31 genotypes) on GC risk. The study was performed in three areas of Mexico, with different GC mortality rates. We included 158 GC patients and 317 clinical controls. Consumption of capsaicin (Cap), the pungent active substance of chili peppers, was estimated by food frequency questionnaire. H. pylori CagA status was assessed by ELISA, and IL1B-31 genotypes were determined by TaqMan assays and Pyrosequencing in DNA samples. Multivariate unconditional logistic regression was used to estimate potential interactions. Moderate to high Cap consumption synergistically increased GC risk in genetically susceptible individuals (IL1B-31C allele carriers) infected with the more virulent H. pylori (CagA+) strains. The combined presence of these factors might explain the absence of a decreasing trend for GC in Mexico. However, further research on gene-environment interactions is required to fully understand the factors determining GC patterns in susceptible populations, with the aim of recommending preventive measures for high risk individuals.

  1. Helicobacter pylori genotyping from American indigenous groups shows novel Amerindian vacA and cagA alleles and Asian, African and European admixture.

    PubMed

    Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Gonzalez-Valencia, Gerardo; Mendoza, Irma; Peñaloza-Espinosa, Rosenda; Ramos, Irma; Kersulyte, Dangeruta; Reyes-Leon, Adriana; Romo, Carolina; Granados, Julio; Muñoz, Leopoldo; Berg, Douglas E; Torres, Javier

    2011-01-01

    It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America.

  2. Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture

    PubMed Central

    Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Gonzalez-Valencia, Gerardo; Mendoza, Irma; Peñaloza-Espinosa, Rosenda; Ramos, Irma; Kersulyte, Dangeruta; Reyes-Leon, Adriana; Romo, Carolina; Granados, Julio; Muñoz, Leopoldo; Berg, Douglas E.; Torres, Javier

    2011-01-01

    It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America. PMID:22073291

  3. Association Between Helicobacter pylori cagA, babA2 Virulence Factors and Gastric Mucosal Interleukin-33 mRNA Expression and Clinical Outcomes in Dyspeptic Patients.

    PubMed

    Shahi, Heshmat; Reiisi, Somayeh; Bahreini, Rasol; Bagheri, Nader; Salimzadeh, Loghman; Shirzad, Hedayatollah

    2015-01-01

    Helicobacter pylori (H. pylori) infection has been reported in more than half of the world human population. It is associated with gastric inflammation and noticeable infiltration of the immune cells to the stomach mucosa by several cytokines secretion. IL-1β, IL-18 have been shown to contribute to H. pylori induced gastritis, but the details of inflammation and association of virulence factors remain unclear. IL-1 cytokine family has a new additional cytokine, Interleukin-33 (IL-33), which is contemplated to have an important role for host defense against microorganisms. H. pylori virulence factors important in gastritis risk are the cag pathogenicity island (cag-PAI) and babA. This study evaluated IL-33 mucosal mRNA expression levels in infected and uninfected patients and its relationship with bacterial virulence factors cagA, babA2 and type of gastritis. Total RNA was extracted from gastric biopsies of 79 H. pylori-infected patients and 51 H. pylori-negative patients. Mucosal IL-33 mRNA expression levels in gastric biopsies were assessed using real-time PCR. Existence of virulence factors were detected by PCR. IL-33 mRNA expression was significantly higher in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients (P<0.0001). Also there was a direct relationship between virulence factor bab-A2 and enhancement in IL-33 mRNA expression. Furthermore, IL-33 mRNA expression level was significantly lower in chronic gastritis patients compared with patients with active gastritis (P<0.001). IL-33 may play a crucial role in the inflammatory response and induction of the chronic gastritis and severity of inflammatory changes in the gastric mucosa.

  4. Association Between Helicobacter pylori cagA, babA2 Virulence Factors and Gastric Mucosal Interleukin-33 mRNA Expression and Clinical Outcomes in Dyspeptic Patients

    PubMed Central

    Shahi, Heshmat; Reiisi, Somayeh; Bahreini, Rasol; Bagheri, Nader; Salimzadeh, Loghman; Shirzad, Hedayatollah

    2015-01-01

    Helicobacter pylori (H. pylori) infection has been reported in more than half of the world human population. It is associated with gastric inflammation and noticeable infiltration of the immune cells to the stomach mucosa by several cytokines secretion. IL-1β, IL-18 have been shown to contribute to H. pylori induced gastritis, but the details of inflammation and association of virulence factors remain unclear. IL-1 cytokine family has a new additional cytokine, Interleukin-33 (IL-33), which is contemplated to have an important role for host defense against microorganisms. H. pylori virulence factors important in gastritis risk are the cag pathogenicity island (cag-PAI) and babA. This study evaluated IL-33 mucosal mRNA expression levels in infected and uninfected patients and its relationship with bacterial virulence factors cagA, babA2 and type of gastritis. Total RNA was extracted from gastric biopsies of 79 H. pylori-infected patients and 51 H. pylori-negative patients. Mucosal IL-33 mRNA expression levels in gastric biopsies were assessed using real-time PCR. Existence of virulence factors were detected by PCR. IL-33 mRNA expression was significantly higher in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients (P<0.0001). Also there was a direct relationship between virulence factor bab-A2 and enhancement in IL-33 mRNA expression. Furthermore, IL-33 mRNA expression level was significantly lower in chronic gastritis patients compared with patients with active gastritis (P<0.001). IL-33 may play a crucial role in the inflammatory response and induction of the chronic gastritis and severity of inflammatory changes in the gastric mucosa. PMID:27014647

  5. Computational approaches for evaluating the effect of sequence variations and the intrinsically disordered C-terminal region of the Helicobacter pylori CagA protein on the interaction with tyrosine kinase Src.

    PubMed

    Delgado, Paula; Peñaranda, Natalia; Zamora, María Antonia; del Pilar Delgado, María; Bohorquez, Eliana; Castro, Harold; Barrios, Andrés Fernando González; Jaramillo, Carlos

    2014-08-01

    The Helicobacter pylori CagA protein was the first bacterial oncoprotein to be identified as important in the development of human malignancies such as gastric cancer. It is not clear how it is able to deregulate a set of cell control mechanisms to induce carcinogenesis following translocation into human gastric epithelial cells. It is likely, however, that structural variations in the CagA sequence alter its affinity with the host proteins inducing differences in the pathogenicity of different H. pylori strains. Using the recently elucidated N-terminal 3D structure of H. pylori CagA, information on the full cagA gene sequence, and intrinsically disordered protein structure predictions methods we evaluated the interaction of different CagA variants with the kinase Src. An automated docking followed by molecular dynamics simulations were performed to explore CagA interaction modes with Src, one of its cellular partners. The computational approach let us establish that even in the presence of the same number and type of EPIYA motifs, CagA protein can reveal different spatial distributions. Based on the lowest affinity energy and higher number of interactions it was established that the principal forces governing the CagA-Src interaction are electrostatic. Results showed that EPIYA-D models presents higher affinity with some host proteins than EPIYA-C. Thus, we highlight the importance and advantage of the use of computational tools in combining chemical and biological data with bioinformatics for modeling and prediction purposes in some cases where experimental techniques present limitations.

  6. In vitro effect of amoxicillin and clarithromycin on the 3’ region of cagA gene in Helicobacter pylori isolates

    PubMed Central

    Bustamante-Rengifo, Javier Andrés; Matta, Andrés Januer; Pazos, Alvaro; Bravo, Luis Eduardo

    2013-01-01

    AIM: To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island (cag PAI). METHODS: One hundred and forty-nine clinical isolates of Helicobacter pylori (H. pylori) cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material. Antimicrobial susceptibility was determined by the agar dilution method. Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping (cagA, vacA alleles s and m), Glu-Pro-Ile-Tyr-Ala (EPIYA) polymerase chain reaction and random amplified polymorphic DNA (RAPD). Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5 program. Cluster analyses was done using SPSS 15.0 statistical package, where each of the fingerprint bands were denoted as variables. Dendrograms were designed by following Ward’s clustering method and the estimation of distances between each pair of H. pylori isolates was calculated with the squared Euclidean distance. RESULTS: Resistance rates were 4% for amoxicillin and 2.7% for clarithromycin with 2% double resistances. Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1. The 3’ region of cagA gene was successfully amplified in 92.3% (12/13) of the baseline resistant isolates and in 60% (36/60) of the resistant isolates growing in antibiotic dilutions. Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates, it was found that in 61.5% (8/13) of the baseline isolates, a change in the number of EPIYA repetitions lowered antibiotic pressure. The gain and loss of EPIYA motifs resulted in a diversity of H. pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure. RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions. CONCLUSION: Antibiotic

  7. Statins Attenuate Helicobacter pylori CagA Translocation and Reduce Incidence of Gastric Cancer: In Vitro and Population-Based Case-Control Studies.

    PubMed

    Lin, Chun-Jung; Liao, Wei-Chih; Lin, Hwai-Jeng; Hsu, Yuan-Man; Lin, Cheng-Li; Chen, Yu-An; Feng, Chun-Lung; Chen, Chih-Jung; Kao, Min-Chuan; Lai, Chih-Ho; Kao, Chia-Hung

    2016-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.

  8. Helicobacter pylori bab Paralog Distribution and Association with cagA, vacA, and homA/B Genotypes in American and South Korean Clinical Isolates.

    PubMed

    Kim, Aeryun; Servetas, Stephanie L; Kang, Jieun; Kim, Jinmoon; Jang, Sungil; Cha, Ho Jin; Lee, Wan Jin; Kim, June; Romero-Gallo, Judith; Peek, Richard M; Merrell, D Scott; Cha, Jeong-Heon

    2015-01-01

    Helicobacter pylori genetic variation is a crucial component of colonization and persistence within the inhospitable niche of the gastric mucosa. As such, numerous H. pylori genes have been shown to vary in terms of presence and genomic location within this pathogen. Among the variable factors, the Bab family of outer membrane proteins (OMPs) has been shown to differ within subsets of strains. To better understand genetic variation among the bab genes and to determine whether this variation differed among isolates obtained from different geographic locations, we characterized the distribution of the Bab family members in 80 American H. pylori clinical isolates (AH) and 80 South Korean H. pylori clinical isolates (KH). Overall, we identified 23 different bab genotypes (19 in AH and 11 in KH), but only 5 occurred in greater than 5 isolates. Regardless of strain origin, a strain in which locus A and locus B were both occupied by a bab gene was the most common (85%); locus C was only occupied in those isolates that carried bab paralog at locus A and B. While the babA/babB/- genotype predominated in the KH (78.8%), no single genotype could account for greater than 40% in the AH collection. In addition to basic genotyping, we also identified associations between bab genotype and well known virulence factors cagA and vacA. Specifically, significant associations between babA at locus A and the cagA EPIYA-ABD motif (P<0.0001) and the vacA s1/i1/m1 allele (P<0.0001) were identified. Log-linear modeling further revealed a three-way association between bab carried at locus A, vacA, and number of OMPs from the HOM family (P<0.002). En masse this study provides a detailed characterization of the bab genotypes from two distinct populations. Our analysis suggests greater variability in the AH, perhaps due to adaptation to a more diverse host population. Furthermore, when considering the presence or absence of both the bab and homA/B paralogs at their given loci and the vac

  9. VacA and CagA Status as Biomarker of Two Opposite End Outcomes of Helicobacter pylori Infection (Gastric Cancer and Duodenal Ulcer) in a Moroccan Population

    PubMed Central

    El Khadir, Mounia; Alaoui Boukhris, Samia; Benajah, Dafr-Allah; El Rhazi, Karima; Ibrahimi, Sidi Adil; El Abkari, Mohamed; Harmouch, Taoufiq; Nejjari, Chakib; Mahmoud, Mustapha; Benlemlih, Mohamed; Bennani, Bahia

    2017-01-01

    Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions leading to gastric cancer. Pathological determinism is associated to some virulence genes of the bacterium, notably the vacA and cagA genes. The present study aimed to determine the H. pylori genotypes distribution and their association with sex, age and gastric diseases in a Moroccan population. Gastric biopsy was taken from 1079 consenting patients. The specimens were processed by PCR to identify H. pylori and to determine the genotypic profile by PCR characterizing vacA s, vacA m and vacA i regions directly from biopsies H. pylori positives. VacA genotyping revealed the predominance of vacA m2 (53.2%), vacA s2 (52.9%) and vacA i2 (52%). The most virulent vacA alleles (s1, i1 and m1) are more predominant in men (47.3%, 41.9% and 46.1% respectively) than in women (38.3%, 33.3% and 37% respectively). However, the association between vacA genotypes and age did not reach a statistical significant value. Logistic regression analysis results show that vacA i1m1 and vacA i1m2 genotypes were strongly associated with the risk of GC, the Odds Ratio (95% confidence interval) was 29.73 [5.08–173.73] and 9.17 [2.06–40.82] respectively, while vacAs1/cagA+ seems to be a risk factor for DU since it is inversely associated with GC (OR was 0.13 [0.02–0.75]. The results of this study suggest that vacA i1 genotype independently to vacAm status may be of a clinical usefulness and will help to identify patients at a high risk of GC development. PMID:28125638

  10. Helicobacter pylori isolated from Iranian drinking water: vacA, cagA, iceA, oipA and babA2 genotype status and antimicrobial resistance properties.

    PubMed

    Ranjbar, Reza; Khamesipour, Faham; Jonaidi-Jafari, Nematollah; Rahimi, Ebrahim

    2016-05-01

    Despite the clinical importance of Helicobacter pylori in human gastric disorders, its exact route of transmission is still uncertain. Based on the contentious hypothesis and findings of previous investigations, water may play an important role in the transmission of H. pylori to humans. This study was carried out to investigate the vacA, cagA, oipA, iceA and babA2 genotype status and antimicrobial resistance properties of H. pylori strains isolated from the drinking water samples of four major provinces in Iran. A total of 400 drinking water samples were cultured and tested. H. pylori-positive strains were analyzed for the presence of various genotypes and antimicrobial resistance. Twelve of 400 (3%) water samples were positive for H. pylori. Samples from Isfahan province had the highest, while those from Shiraz had the lowest prevalence of H. pylori. The seasonal distribution was also determined, with the highest prevalence of bacteria in the summer season (7.36%). H. pylori strains harbored the highest levels of resistance against ampicillin (100%), erythromycin (75%), clarithromycin (75%), and trimethoprim (58.3%). The most commonly detected genotypes were vacAs1a (83.3%), vacAm1a (66.6%), vacAs2 (50%) and cagA (50%). The presence of similar genotypes in the H. pylori strains of drinking water and those of human clinical samples suggest that contaminated water maybe the sources of bacteria. Spiramycin and furazolidone are suggested for the treatment of cases of H. pylori infection.

  11. Difluoromethylornithine Is a Novel Inhibitor of Helicobacter pylori Growth, CagA Translocation, and Interleukin-8 Induction

    PubMed Central

    Barry, Daniel P.; Asim, Mohammad; Leiman, David A.; de Sablet, Thibaut; Singh, Kshipra; Casero, Robert A.; Chaturvedi, Rupesh; Wilson, Keith T.

    2011-01-01

    Helicobacter pylori infects half the world's population, and carriage is lifelong without antibiotic therapy. Current regimens prescribed to prevent infection-associated diseases such as gastroduodenal ulcers and gastric cancer can be thwarted by antibiotic resistance. We reported that administration of 1% d,l-α-difluoromethylornithine (DFMO) to mice infected with H. pylori reduces gastritis and colonization, which we attributed to enhanced host immune response due to inhibition of macrophage ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Although no ODC has been identified in any H. pylori genome, we sought to determine if DFMO has direct effects on the bacterium. We found that DFMO significantly reduced the growth rate of H. pylori in a polyamine-independent manner. Two other Gram-negative pathogens possessing ODC, Escherichia coli and Citrobacter rodentium, were resistant to the DFMO effect. The effect of DFMO on H. pylori required continuous exposure to the drug and was reversible when removed, with recovery of growth rate in vitro and the ability to colonize mice. H. pylori exposed to DFMO were significantly shorter in length than those untreated and they contained greater internal levels of ATP, suggesting severe effects on bacterial metabolism. DFMO inhibited expression of the H. pylori virulence factor cytotoxin associated gene A, and its translocation and phosphorylation in gastric epithelial cells, which was associated with a reduction in interleukin-8 expression. These findings suggest that DFMO has effects on H. pylori that may contribute to its effectiveness in reducing gastritis and colonization and may be a useful addition to anti-H. pylori therapies. PMID:21386987

  12. Prevalence of Helicobacter pylori vacA, cagA, cagE, oipA, iceA, babA2 and babB genotypes in Iranian dyspeptic patients.

    PubMed

    Dabiri, Hossein; Jafari, Fereshteh; Baghaei, Kaveh; Shokrzadeh, Leila; Abdi, Saeed; Pourhoseingholi, Mohamad Amin; Mohammadzadeh, Alireza

    2017-04-01

    There is diversity in clinical outcome of Helicobacter pylori infection in different regions. Microbial, host and environmental factors seem to be reason of such variation. Considering microbial factors, we studied H. pylori genotypes and their association with clinical feature of the infection. Overall 160 H. pylori-positive patients were enrolled in this study. Clinical information and biopsy were collected from each patient. The presence of the major virulence genes were determined by PCR. Regardless to clinical outcomes, vacA, cagA, cagE, oipA, iceA1, babA2 and babB genes was positive in 100%, 69%, 51%, 55%, 26%,78% and 28% of 160 strains respectively. The s1m2 was more common vacA allels and s1a and m1a were predominant s and m regions. In patient with gastric cancer (GC), the oipA was less frequent while the iceA1 was the most common. The babA2 was common in all patient groups. The babB was significantly observed in strains isolated from patients with GC. There were significant association among cagA status with presence of vacAs1, vacAm2, cagE, oipA, iceA1 and babA2. Presence of the babB and oipA was connected with higher and lower risk for GC respectively. There was no association between the cagA, vacA, cagE or iceA status and clinical outcome in patients in Iran. We showed that presence of the babB and iceA1 were significantly connected with higher risk for gastric cancer development in Iranian dyspeptic patients while H. pylori isolates with positive oipA had little threat for leading patients to cancer.

  13. Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer Vaccine

    PubMed Central

    Stein, Markus; Ruggiero, Paolo; Rappuoli, Rino; Bagnoli, Fabio

    2013-01-01

    Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial to mesenchymal transition (EMT) through the injection of cytotoxin-associated gene A into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell–cell and cell–matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg) have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers. PMID:24133496

  14. Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome.

    PubMed

    Tiwari, Santosh K; Sharma, Vishwas; Sharma, Varun Kumar; Gopi, Manoj; Saikant, R; Nandan, Amrita; Bardia, Avinash; Gunisetty, Sivaram; Katikala, Prasanth; Habeeb, Md Aejaz; Khan, Aleem A; Habibullah, C M

    2011-04-01

    The population of India harbors one of the world's most highly diverse gene pools, owing to the influx of successive waves of immigrants over regular periods in time. Several phylogenetic studies involving mitochondrial DNA and Y chromosomal variation have demonstrated Europeans to have been the first settlers in India. Nevertheless, certain controversy exists, due to the support given to the thesis that colonization was by the Austro-Asiatic group, prior to the Europeans. Thus, the aim was to investigate pre-historic colonization of India by anatomically modern humans, using conserved stretches of five amino acid (EPIYA) sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H. pylori strains isolated from subjects with several forms of gastric diseases, was also explored. High resolution sequence analysis of the above described genes was performed. The nucleotide sequences obtained were translated into amino acids using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of the study suggest that Indian H. pylori strains share a common ancestry with Europeans. No specific association of haplotypes with the outcome of disease was revealed through additional network analysis of TPMs.

  15. CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease.

    PubMed

    Kato, S; Sugiyama, T; Kudo, M; Ohnuma, K; Ozawa, K; Iinuma, K; Asaka, M; Blaser, M J

    2000-01-01

    cagA(+) Helicobacter pylori strains have been linked to more severe gastric inflammation, peptic ulcer disease, and gastric cancer in adults, but there have been few studies of cagA in children. We examined the relationship between H. pylori cagA status and clinical status in Japanese children. Forty H. pylori-positive children were studied: 15 with nodular gastritis, 5 with gastric ulcers, and 20 with duodenal ulcers. H. pylori status was confirmed by biopsy-based tests and serum anti-H. pylori immunoglobulin G (IgG) antibody. As controls, 77 asymptomatic children with sera positive for anti-H. pylori IgG were enrolled. Levels of IgG antibodies to CagA in serum were measured by an antigen-specific enzyme-linked immunosorbent assay. In 16 patients with successful H. pylori eradication, posttreatment levels of CagA and H. pylori IgG antibodies also were studied. The CagA antibody seropositivities of asymptomatic controls (81.8%) and patients with nodular gastritis, gastric ulcers, and duodenal ulcers (80.0 to 95.0%) were not significantly different. Compared with pretreatment levels of CagA antibodies, posttreatment levels decreased progressively and significantly. We conclude that, as in Japanese adults, a high prevalence of cagA(+) H. pylori strains was found in Japanese children, and that there was no association with nodular gastritis or peptic ulcer disease. In the assessment of eradicative therapies, monitoring of serum anti-CagA antibodies does not appear to offer any direct benefit over monitoring of anti-H. pylori antibodies.

  16. Identification of cagA tyrosine phosphorylation DNA motifs in Helicobacter pylori isolates from peptic ulcer patients by novel PCR-restriction fragment length polymorphism and real-time fluorescence PCR assays.

    PubMed

    Owen, Robert J; Sharp, Sally I; Chisholm, Stephanie A; Rijpkema, Sjoerd

    2003-07-01

    Cag pathogenicity island-containing Helicobacter pylori (type I) induces signal transduction pathways resulting in tyrosine phosphorylation of proteins adjacent to the site of bacterial adhesion on host gastric epithelial cells. Conventional block PCR-restriction fragment length polymorphism (RFLP) and real-time LightCycler (LC) PCR hybridization assays, validated by direct sequencing, were designed to test for the presence of three nucleotide sequences corresponding to tyrosine phosphorylation motifs (TPMs) A, B, and C in 84 isolates of H. pylori type I from patients in England. Overall, the PCR assays demonstrated that one or more TPMs were present in 62 strains (75%). Motif A was common (71% of strains), whereas motifs B and C were rarer (8% of strains). Strains lacking a TPM were typically vacuolating cytotoxin genotype vacA m2. Motif A was widely distributed in relation to disease severity and was more commonly (but not significantly [P = 0.071]) associated with gastric ulcer than with duodenal ulcer (86 versus 56%). The LC hybridization assay provided a rapid means of detecting all three motifs, but RFLP analysis was more specific for TPM-A. TPMs provide novel additional strain markers for defining cagA variation, including identification of RFLP types within TPM-A. The presence of a particular TPM was not of direct diagnostic value, either singly or in combination, but the higher proportion of TPM-A strains in gastric ulcer patients merits further investigation.

  17. Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pylori IgG and IgA in Children.

    PubMed

    Seo, Ji-Hyun; Lim, Chun Woo; Park, Ji Sook; Yeom, Jung Sook; Lim, Jae-Young; Jun, Jin-Su; Woo, Hyang-Ok; Youn, Hee-Shang; Baik, Seung-Chul; Lee, Woo-Kon; Cho, Myung-Je; Rhee, Kwang-Ho

    2016-03-01

    We tested correlations between anti-Helicobacter pylori IgG and IgA levels and the urease test, anti-CagA protein antibody, degree of gastritis, and age. In total, 509 children (0-15 years) were enrolled. Subjects were stratified as 0-4 years (n = 132), 5-9 years (n = 274), and 10-15 years (n = 103) and subjected to the urease test, histopathology, ELISA, and western blot using whole-cell lysates of H. pylori strain 51. The positivity rate in the urease test (P = 0.003), the degree of chronic gastritis (P = 0.021), and H. pylori infiltration (P < 0.001) increased with age. The median titer for anti-H. pylori IgG was 732.5 IU/mL at 0-4 years, 689.0 IU/mL at 5-9 years, and 966.0 IU/mL at 10-15 years (P < 0.001); the median titer for anti-H. pylori IgA was 61.0 IU/mL at 0-4 years, 63.5 IU/mL at 5-9 years, and 75.0 IU/mL at 10-15 years (P < 0.001). The CagA-positivity rate was 26.5% at 0-4 years, 36.5% at 5-9 years, and 46.6% at 10-15 years for IgG (P = 0.036), and 11.3% at 0-4 years, 18.6% at 5-9 years, and 23.3% at 10-15 years for IgA (P < 0.001). Anti-H. pylori IgG and IgA titers increased with the urease test grade, chronic gastritis degree, active gastritis, and H. pylori infiltration. Presence of CagA-positivity is well correlated with a high urease test grade and high anti-H. pylori IgG/IgA levels.

  18. Echoes of a Distant Past: The cag Pathogenicity Island of Helicobacter pylori

    PubMed Central

    Pacchiani, Nicola; Censini, Stefano; Buti, Ludovico; Covacci, Antonello

    2013-01-01

    This review discusses the multiple roles of the CagA protein encoded by the cag pathogenicity island of Helicobacter pylori and highlights the CagA degradation activities on p53. By subverting the p53 tumor suppressor pathway CagA induces a strong antiapoptotic effect. Helicobacter pylori infection has been always associated with an increased risk of gastric cancer. The pro-oncogenic functions of CagA also target the tumor suppressor ASPP2. In the absence of tumor suppressor genes, cells survive and proliferate at times and in places where their survival and proliferation are inappropriate. PMID:24097901

  19. babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil.

    PubMed

    Oliveira, Adriana Gonçalves; Santos, Adriana; Guerra, Juliana Becattini; Rocha, Gifone Aguiar; Rocha, Andreia Maria Camargos; Oliveira, Celso Affonso; Cabral, Mônica Maria Demas Alvares; Nogueira, Ana Margarida Miguel Ferreira; Queiroz, Dulciene Maria Magalhães

    2003-08-01

    The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.

  20. Immune Responses to "Helicobacter pylori" Infection in Children with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Douraghi, Masoumeh; Goudarzi, Hossein; Rostami, Mahmoud Nateghi; Nikmanesh, Bahram

    2012-01-01

    Infection with "Helicobacter pylori" was assessed through serum "H. pylori" IgG antibody in children with intellectual disabilities (ID). The sero-status of cytotoxin-associated gene A (CagA) was determined as a risk determinant for severe "H. pylori"-associated diseases. In total, 210 children with ID were included…

  1. Prevalence of CagA and VacA antibodies in children with Helicobacter pylori-associated peptic ulcer compared to prevalence in pediatric patients with active or nonactive chronic gastritis.

    PubMed

    Alarcón, T; Martínez, M J; Urruzuno, P; Cilleruelo, M L; Madruga, D; Sebastian, M; Domingo, D; Sanz, J C; López-Brea, M

    2000-09-01

    VacA and CagA serological responses were detected in pediatric patients: 44 and 56%, respectively, in peptic ulcer (PU) patients, 33.3 and 44.4% in active chronic gastritis (ACG) patients, and 23.2 and 39.2% in non-ACG patients. Higher seroprevalence to CagA+VacA and to CagA+VacA+35-kDa antigen was found among PU patients. However, a low level of sensitivity and specificity was found for indirect detection of PU patients.

  2. Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries.

    PubMed

    Yamaoka, Y; Osato, M S; Sepulveda, A R; Gutierrez, O; Figura, N; Kim, J G; Kodama, T; Kashima, K; Graham, D Y

    2000-02-01

    The predominant H. pylori strain circulating among geographic locations differs with regard to the genomic structure. This study determined whether structural subtypes of the cagA 3' repeat region could be used to identify the population of origin of H. pylori isolates. We examined 600 cagA-positive H. pylori (Colombia, 100; USA, 100; France, 100; Canada, 20; Italy, 20; Korea, 100; Japan, 100; Hong Kong, 20; Taiwan, 20; Vietnam, 20). The cagA 3' region was amplified by PCR using primers specific to Japanese and Western 3' cagA gene sequences. PCR using Japanese cagA primers resulted in PCR products in 99-6 % of strains from East Asia but no non-Asian strains. Conversely, PCR using Western cagA primers resulted in amplicons in 100% of non-Asian strains, and only one from East Asia. cagA genotyping is useful for molecular epidemiological studies as strains can be completely separated by differences in the cagA 3' region.

  3. Relation between periodontitis and helicobacter pylori infection

    PubMed Central

    Zheng, Pei; Zhou, Weiying

    2015-01-01

    Objective: The correlation between periodontitis and Helicobacter pylori (H. pylori) infection in the mouth was analyzed. Method: 70 elderly patients with periodontitis treated at our hospital from January 2013 to December 2014 were recruited. Dental plaques and gargle were collected for H. pylori detection using PCR technique. Periodontal health status of the patients was recorded. 70 control cases with healthy periodontium were also included. The symptoms of H. pylori infection in the mouth were compared between the two groups, and the results were analyzed statistically. Results: The positive rate of urease C gene of H. pylori in the periodontitis group was 71.4%; the positive rate of cagA gene was 35.7%. The positive rate of urease C gene of H. pylori in the control group was 34.3% and that of cagA gene was 12.9%. The two groups did not show significant differences in these two indicators (P<0.05). The positive detection rate of urease C gene of H. pylori in subgingival plaques was higher than that in supragingival plaques, and the difference was of statistical significance (P<0.05). The positive detection rate of H. pylori in patients with moderate and severe periodontitis was obviously higher than that of patients with mild periodontitis (P<0.05). Conclusion: Periodontal health status of elderly people with periodontitis correlated with H. pylori infection in the stomach. PMID:26629215

  4. Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion.

    PubMed

    Hammond, Charles E; Beeson, Craig; Suarez, Giovanni; Peek, Richard M; Backert, Steffen; Smolka, Adam J

    2015-08-01

    Acute Helicobacter pylori infection of gastric epithelial cells and human gastric biopsies represses H,K-ATPase α subunit (HKα) gene expression and inhibits acid secretion, causing transient hypochlorhydria and supporting gastric H. pylori colonization. Infection by H. pylori strains deficient in the cag pathogenicity island (cag PAI) genes cagL, cagE, or cagM, which do not transfer CagA into host cells or induce interleukin-8 secretion, does not inhibit HKα expression, nor does a cagA-deficient strain that induces IL-8. To test the hypothesis that virulence factors other than those mediating CagA translocation or IL-8 induction participate in HKα repression by activating NF-κB, AGS cells transfected with HKα promoter-Luc reporter constructs containing an intact or mutated NF-κB binding site were infected with wild-type H. pylori strain 7.13, isogenic mutants lacking cag PAI genes responsible for CagA translocation and/or IL-8 induction (cagA, cagζ, cagε, cagZ, and cagβ), or deficient in genes encoding two peptidoglycan hydrolases (slt and cagγ). H. pylori-induced AGS cell HKα promoter activities, translocated CagA, and IL-8 secretion were measured by luminometry, immunoblotting, and ELISA, respectively. Human gastric biopsy acid secretion was measured by microphysiometry. Taken together, the data showed that HKα repression is independent of IL-8 expression, and that CagA translocation together with H. pylori transglycosylases encoded by slt and cagγ participate in NF-κB-dependent HKα repression and acid inhibition. The findings are significant because H. pylori factors other than CagA and IL-8 secretion are now implicated in transient hypochlorhydria which facilitates gastric colonization and potential triggering of epithelial progression to neoplasia.

  5. Association between Helicobacter pylori Virulence Factors and Gastroduodenal Diseases in Okinawa, Japan

    PubMed Central

    Matsunari, Osamu; Shiota, Seiji; Suzuki, Rumiko; Watada, Masahide; Kinjo, Nagisa; Murakami, Kazunari; Fujioka, Toshio; Kinjo, Fukunori

    2012-01-01

    The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of Helicobacter pylori with Western-type cagA in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type cagA strains is high in Okinawa. We examined the association between the virulence factors of H. pylori and gastroduodenal diseases in Okinawa. The genotypes of cagA and vacA of 337 H. pylori strains were determined by PCR and gene sequencing. The genealogy of these Western-type cagA strains in Okinawa was analyzed by multilocus sequence typing (MLST). Overall, 86.4% of the strains possessed cagA: 70.3% were East-Asian type and 16.0% were Western type. After adjustment by age and sex, the presence of East-Asian-type cagA/vacA s1m1 genotypes was significantly associated with gastric cancer compared to gastritis (odds ratio = 6.68, 95% confidence interval = 1.73 to 25.8). The structure of Western-type CagA in Okinawa was different from that of typical Western-type CagA found in Western countries. Intriguingly, MLST analysis revealed that the majority of Western-type cagA strains formed individual clusters but not hpEurope. Overall, low prevalence of gastric cancer in Okinawa may result from the high prevalence of non-East-Asian-type cagA strains. The origin of Western-type cagA strains in Okinawa may be different from those of Western countries. PMID:22189111

  6. Association between Helicobacter pylori virulence factors and gastroduodenal diseases in Okinawa, Japan.

    PubMed

    Matsunari, Osamu; Shiota, Seiji; Suzuki, Rumiko; Watada, Masahide; Kinjo, Nagisa; Murakami, Kazunari; Fujioka, Toshio; Kinjo, Fukunori; Yamaoka, Yoshio

    2012-03-01

    The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of Helicobacter pylori with Western-type cagA in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type cagA strains is high in Okinawa. We examined the association between the virulence factors of H. pylori and gastroduodenal diseases in Okinawa. The genotypes of cagA and vacA of 337 H. pylori strains were determined by PCR and gene sequencing. The genealogy of these Western-type cagA strains in Okinawa was analyzed by multilocus sequence typing (MLST). Overall, 86.4% of the strains possessed cagA: 70.3% were East-Asian type and 16.0% were Western type. After adjustment by age and sex, the presence of East-Asian-type cagA/vacA s1m1 genotypes was significantly associated with gastric cancer compared to gastritis (odds ratio = 6.68, 95% confidence interval = 1.73 to 25.8). The structure of Western-type CagA in Okinawa was different from that of typical Western-type CagA found in Western countries. Intriguingly, MLST analysis revealed that the majority of Western-type cagA strains formed individual clusters but not hpEurope. Overall, low prevalence of gastric cancer in Okinawa may result from the high prevalence of non-East-Asian-type cagA strains. The origin of Western-type cagA strains in Okinawa may be different from those of Western countries.

  7. Regulation of Helicobacter pylori Virulence Within the Context of Iron Deficiency.

    PubMed

    Noto, Jennifer M; Lee, Josephine Y; Gaddy, Jennifer A; Cover, Timothy L; Amieva, Manuel R; Peek, Richard M

    2015-06-01

    Helicobacter pylori strains that harbor the oncoprotein CagA increase gastric cancer risk, and this risk is augmented under iron-deficient conditions. We demonstrate here that iron depletion induces coccoid morphology in strains lacking cagA. To evaluate the stability of augmented H. pylori virulence phenotypes stimulated by low-iron conditions, H. pylori isolated from iron-depleted conditions in vivo were serially passaged in vitro. Long-term passage decreased the ability of hypervirulent strains to translocate CagA or induce interleukin 8, indicating that hypervirulent phenotypes stimulated by low-level iron conditions are reversible. Therefore, rectifying iron deficiency may attenuate disease among H. pylori-infected persons with no response to antibiotics.

  8. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis.

    PubMed

    Gaddy, Jennifer A; Radin, Jana N; Loh, John T; Zhang, Feng; Washington, M Kay; Peek, Richard M; Algood, Holly M Scott; Cover, Timothy L

    2013-06-01

    Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA(+) H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P < 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA(+) H. pylori strains.

  9. Helicobacter pylori and Its Virulence Factors' Effect on Serum Oxidative DNA Damages in Adults With Dyspepsia.

    PubMed

    Shahi, Heshmat; Bahreiny, Rasoul; Reiisi, Somayeh

    2016-11-01

    Helicobacter Pylori infection is a common gastrointestinal infection that can cause pathological effects, increase oxidative stress and induce an inflammatory response in gastric mucosa. Inflammatory aspects may prompt the production of radical oxygen substance (ROS) which may damage cells and release 8-hydroxydyoxyguanosine (8-OHdG) to serum. In this study, we evaluate the prevalence of H. pylori virulence factors and the association between serum level of 8-OHdG, H. pylori infection, and its various virulence factors. The presence of H. pylori and prevalence of cagA, babA and oipA genes in samples were determined by rapid urease test (RUT), histopathological exam (HE) and polymerase chain reaction (PCR) and oxidative DNA damage situation were assessed by using serum level of 8-OHdG. There was not any direct relation between H. pylori negative and H. pylori oipA+specimens by 8-OHdG serum level (P>0.05). In all clinical observations, the presence of cagA and oipA genes was common. There was a statistical relationship between the presence of cagA, babA factors, and high serum level of 8-OHdG (P<0.05). The presence of cagA and babA virulence factors may be associated with increased serum 8-OHdG in dyspeptic patients and may induce the damage to gastric cells.

  10. Relationship between Helicobacter pylori Virulence Genes and Clinical Outcomes in Saudi Patients

    PubMed Central

    2012-01-01

    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 s- and 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. PMID:22323867

  11. Can Helicobacter pylori infection influence human reproduction?

    PubMed

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-05-21

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.

  12. Can Helicobacter pylori infection influence human reproduction?

    PubMed Central

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-01-01

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction. PMID:24914316

  13. Effect of Helicobacter pylori infection on chronic periodontitis by the change of microecology and inflammation

    PubMed Central

    Hu, Zhekai; Zhang, Yu; Li, Zhiyu; Yu, Yuedi; Kang, Wenyan; Han, Yingnan; Geng, Xiwen; Ge, Shaohua; Sun, Yundong

    2016-01-01

    Helicobacter pylori (H. pylori), a pathogen inducing peptic disease, is recently found to be binding to the progress of periodontitis. Most previous studies are case-controlled, and they investigate the risk of H. pylori infection in disease the development of while few studies evaluate the correlation between H. pylori and periodontal pathogens. Therefore, we investigated the correlation between H. pylori infection with periodontal parameters, periodontal pathogens and inflammation. The results indicated that patients with H. pylori showed significantly higher probing depth and attachment loss than those without (p < 0.05). Among 28 subgingival plaque samples from 14 patients, the frequencies of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Treponema denticola were significantly higher with H. pylori infection than those without H. pylori infection (p < 0.05). However, the frequency of Aggregatibacter actinomycetemcomitans was lower (p < 0.05). Furthermore, after human acute monocytic leukemia cell line (THP-1) was stimulated with cagA-positive standard strains (cagA+ H. pylori 26695), the expression of periodontitis-related molecules Wnt5a, interleukin 8 (IL-8), interleukin 6 (IL-6) and interferon gamma (IFN-γ) significantly increased (p < 0.05). Conversely, the expression of tumor necrosis factor alpha (TNF-α) was almost stable. Meanwhile, cagA+ H. pylori promoted significantly higher expression of IL-8 and Wnt5a than isogenic cagA mutants strains (cagA− H. pylori 26695) did. Taken together, our data suggested that H. pylori might promote the growth of some periodontal pathogens and aggravate the progress of chronic periodontitis. PMID:27602578

  14. Helicobacter pylori

    MedlinePlus

    ... illnesses. H. pylori , which used to be called Campylobacter pylori , also can cause peptic ulcers (commonly known ... H. Pylori Antigen Food Safety for Your Family Campylobacter Infections Pyloric Stenosis Peptic Ulcers Digestive System Vomiting ...

  15. Helicobacter pylori virulence factors as tools to study human migrations.

    PubMed

    Queiroz, Dulciene Maria de Magalhães; Cunha, Roberto Penna de Almeida; Saraiva, Ivan Euclides Borges; Rocha, Andreia Maria Camargos

    2010-12-15

    Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA and vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.

  16. Role of dupA in virulence of Helicobacter pylori.

    PubMed

    Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo

    2016-12-14

    Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.

  17. Role of dupA in virulence of Helicobacter pylori

    PubMed Central

    Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo

    2016-01-01

    Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery. PMID:28028359

  18. Changes in biological and virulent characteristics of Helicobacter pylori exposed to high salt.

    PubMed

    Xu, Ying; Jing, Jing-Jing; Gong, Yue-Hua; Xu, Qian; Zhang, Wen-Lu; Piao, Ying; Wang, Yan-Li; Yuan, Yuan

    2011-01-01

    The effect of high salt environments on biological characteristics of Helicobacter pylori is still unclear. In the present study, we therefore investigated biological characteristics of the bacterium exposed to high salt concentrations. H. pylori strain, L301, was cultured in media supplemented with different concentrations (3%, 15% and 30%) of sodium chloride (NaCl) under microaerophilic conditions for 48 h. Morphology was assessed by light microscopy, the ATP content was quantitated by single-tube fluorescent light-emission and the levels of CagA and UreB proteins were determined by Western blotting. After exposure to NaCl, H. pylori transformed from common spiral shape to U or even coccoid shapes. The ATP content was significantly higher in 30% NaCl group than in 15% and 3% NaCl group and the level of CagA protein increased with the salt concentration. The urease reaction was all strongly positive in H. pylori exposed to different salt concentrations. The level of 8-OHdG expression was significantly increased in GES-1 cells co-cultured with H. pylori exposed to high salt, compared with the level in uninfected cells. H. pylori survives under exposure to high salt concentrations up to 30%, exhibiting changes in mobility, morphology and CagA expression, associated with increased 8-OHdG in the gastric epithelial cells, indicative of DNA damage.

  19. Detection of cytoplasmic proteins from Helicobacter pylori in Colony Lift Immunoassay.

    PubMed

    Rojas-Rengifo, Diana F; Jaramillo, Carlos A; Haas, Rainer; Jiménez-Soto, Luisa F

    2015-12-01

    Use of the Colony Lift Immunoassay has been described for several Gram negative bacteria of medical interest. In all cases detection was limited to the use of antibodies against outer membrane proteins. Here we describe the adaptation of this method for detection of the cytoplasmic CagA toxin from Helicobacter pylori.

  20. Lewis Antigen Expression by Helicobacter pylori Strains Colonizing Different Regions of the Stomach of Individual Patients▿

    PubMed Central

    González-Valencia, Gerardo; Muñoz-Perez, Leopoldo; Morales-Espinosa, Rosario; Camorlinga-Ponce, Margarita; Muñoz, Onofre; Torres, Javier

    2008-01-01

    The diversity in the expression of Lewis antigens (Le) of 226 single colonies of Helicobacter pylori isolated from four regions of the stomach of eight adults is shown. Ley was expressed more in strains colonizing antrum than in strains colonizing fundus, whereas Lex was more common in fundus strains. cagA+ strains were more associated with Le-negative strains. PMID:18550746

  1. Assessment of Risk and Sero-Prevalence of Helicobacter pylori Colonization among Remote Orang Asli Tribes in Peninsula Malaysia.

    PubMed

    Thevakumar, Kavitha; Chandren, Josephine Rebecca; Perez-Perez, Guillermo Ignacio; Chua, Eng Guan; Teh, Lay Kek; Salleh, Mohd Zaki; Tan, Jin Ai Mary Anne; Leow, Alex Hwong Ruey; Goh, Khean Lee; Tay, Alfred Chin Yen; Marshall, Barry J; Vadivelu, Jamuna; Loke, Mun Fai; Wong, Li Ping

    2016-01-01

    The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes.

  2. Assessment of Risk and Sero-Prevalence of Helicobacter pylori Colonization among Remote Orang Asli Tribes in Peninsula Malaysia

    PubMed Central

    Thevakumar, Kavitha; Chandren, Josephine Rebecca; Perez-Perez, Guillermo Ignacio; Chua, Eng Guan; Teh, Lay Kek; Salleh, Mohd Zaki; Tan, Jin Ai Mary Anne; Leow, Alex Hwong Ruey; Goh, Khean Lee; Tay, Alfred Chin Yen; Marshall, Barry J.; Vadivelu, Jamuna; Loke, Mun Fai; Wong, Li Ping

    2016-01-01

    The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes. PMID:27441568

  3. Characteristics of clinical Helicobacter pylori strains from Ecuador.

    PubMed

    Debets-Ossenkopp, Yvette J; Reyes, Germán; Mulder, Janet; aan de Stegge, Birgit M; Peters, José T A M; Savelkoul, Paul H M; Tanca, J; Peña, Amado S; Vandenbroucke-Grauls, Christina M J E

    2003-01-01

    In Ecuador, Helicobacter pylori infections are highly prevalent. A total of 42 H. pylori clinical isolates from 86 patients attending the outpatient clinic of the gastroenterology department of the university hospital of Guayaquil in Ecuador were characterized. Their susceptibility, and cagA and vacA status were determined. Resistance to metronidazole and clarithromycin was found in 80.9% and 9.5% of strains, respectively. Neither amoxicillin- nor tetracycline-resistant strains were found. The most prevalent genotype was the cagA(+), vacA s1b,m1 type. This genotype was associated with gastric cancer and peptic ulcer. Typing by random amplified polymorphic DNA showed no genetic relationship among the strains.

  4. H pylori status and angiogenesis factors in human gastric carcinoma

    PubMed Central

    Mangia, Anita; Chiriatti, Annalisa; Ranieri, Girolamo; Abbate, Ines; Coviello, Maria; Simone, Giovanni; Zito, Francesco Alfredo; Montemurro, Severino; Rucci, Antonello; Leo, Alfredo Di; Tommasi, Stefania; Berloco, Pasquale; Xu, Jian Ming; Paradiso, Angelo

    2006-01-01

    AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent. PMID:17006982

  5. Medicinal plant activity on Helicobacter pylori related diseases

    PubMed Central

    Wang, Yuan-Chuen

    2014-01-01

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori

  6. [IMMUNOLOGIC MONITORING OF HELICOBACTER PYLORI PERSISTENCE IN THE ORGANISM].

    PubMed

    Belaya, Yu A; Belaya, O F; Petrukhin, V G; Vakhrameeva, M S; Bystrova, S M; Pronin, A V

    2015-01-01

    Generalized results of 15-year prospective studies of frequency of occurrence and dynamics of circulation of pathogenetically significant LPS/O-antigens, high molecular weight proteins, including CagA, and VacA of Helicobacter pylori in biological media of organism in patients with gastrointestinal diseases and asymptomatic volunteers due to effects of external and internal factors are presented. Features of antigen circulation and reciprocal immune reaction of the organism are established, that reflect their interaction in the parasite-host tandem, risk and prognosis of possible complications in the process of long-term persistence of Helicobacter pylori in the organism.

  7. Heme oxygenase-1 dysregulates macrophage polarization and the immune response to Helicobacter pylori.

    PubMed

    Gobert, Alain P; Verriere, Thomas; Asim, Mohammad; Barry, Daniel P; Piazuelo, M Blanca; de Sablet, Thibaut; Delgado, Alberto G; Bravo, Luis E; Correa, Pelayo; Peek, Richard M; Chaturvedi, Rupesh; Wilson, Keith T

    2014-09-15

    Helicobacter pylori incites a futile inflammatory response, which is the key feature of its immunopathogenesis. This leads to the ability of this bacterial pathogen to survive in the stomach and cause peptic ulcers and gastric cancer. Myeloid cells recruited to the gastric mucosa during H. pylori infection have been directly implicated in the modulation of host defense against the bacterium and gastric inflammation. Heme oxygenase-1 (HO-1) is an inducible enzyme that exhibits anti-inflammatory functions. Our aim was to analyze the induction and role of HO-1 in macrophages during H. pylori infection. We now show that phosphorylation of the H. pylori virulence factor cytotoxin-associated gene A (CagA) in macrophages results in expression of hmox-1, the gene encoding HO-1, through p38/NF (erythroid-derived 2)-like 2 signaling. Blocking phagocytosis prevented CagA phosphorylation and HO-1 induction. The expression of HO-1 was also increased in gastric mononuclear cells of human patients and macrophages of mice infected with cagA(+) H. pylori strains. Genetic ablation of hmox-1 in H. pylori-infected mice increased histologic gastritis, which was associated with enhanced M1/Th1/Th17 responses, decreased regulatory macrophage (Mreg) response, and reduced H. pylori colonization. Gastric macrophages of H. pylori-infected mice and macrophages infected in vitro with this bacterium showed an M1/Mreg mixed polarization type; deletion of hmox-1 or inhibition of HO-1 in macrophages caused an increased M1 and a decrease of Mreg phenotype. These data highlight a mechanism by which H. pylori impairs the immune response and favors its own survival via activation of macrophage HO-1.

  8. Heme Oxygenase-1 Dysregulates Macrophage Polarization and the Immune Response to Helicobacter pylori

    PubMed Central

    Gobert, Alain P.; Verriere, Thomas; Asim, Mohammad; Barry, Daniel P.; Piazuelo, M. Blanca; de Sablet, Thibaut; Delgado, Alberto G.; Bravo, Luis E.; Correa, Pelayo; Peek, Richard M.; Chaturvedi, Rupesh; Wilson, Keith T.

    2014-01-01

    Helicobacter pylori incites a futile inflammatory response, which is the key feature of its immunopathogenesis. This leads to the ability of this bacterial pathogen to survive in the stomach and cause peptic ulcers and gastric cancer. Myeloid cells recruited to the gastric mucosa during Helicobacter pylori infection have been directly implicated in the modulation of host defense against the bacterium and gastric inflammation. Heme oxygenase-1 (HO-1) is an inducible enzyme that exhibits anti-inflammatory functions. Our aim was to analyze the induction and role of HO-1 in macrophages during H. pylori infection. We now show that phosphorylation of the H. pylori virulence factor cytotoxin associated gene A (CagA) in macrophages results in expression of hmox-1, the gene encoding HO-1, through p38/nuclear factor (erythroid-derived 2)-like 2 signaling. Blocking phagocytosis prevented CagA phosphorylation and HO-1 induction. The expression of HO-1 was also increased in gastric mononuclear cells of human patients and macrophages of mice infected with cagA+ H. pylori strains. Genetic ablation of hmox-1 in H. pylori-infected mice increased histologic gastritis, which was associated with enhanced M1/Th1/Th17 responses, decreased Mreg response, and reduced H. pylori colonization. Gastric macrophages of H. pylori-infected mice and macrophages infected in vitro with this bacterium showed an M1/Mreg mixed polarization type; deletion of hmox-1 or inhibition of HO-1 in macrophages caused an increased M1 and a decreased of Mreg phenotype. These data highlight a mechanism by which H. pylori impairs the immune response and favors its own survival via activation of macrophage HO-1. PMID:25108023

  9. Helicobacter pylori Outer Membrane Protein-Related Pathogenesis.

    PubMed

    Matsuo, Yuichi; Kido, Yasutoshi; Yamaoka, Yoshio

    2017-03-11

    Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system.

  10. Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

    PubMed Central

    Matsuo, Yuichi; Kido, Yasutoshi; Yamaoka, Yoshio

    2017-01-01

    Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system. PMID:28287480

  11. Helicobacter pylori Infection in Rural and Urban Dyspeptic Patients from Venezuela

    PubMed Central

    Contreras, Monica; Fernández-Delgado, Milagro; Reyes, Nelson; García-Amado, María Alexandra; Rojas, Héctor; Michelangeli, Fabian

    2015-01-01

    The goal of this work was to assess the Helicobacter pylori prevalence in a rural mestizo population and compare it to an urban population from Venezuela. The study was performed in gastric juice samples of 71 dyspeptic patients from Caracas (urban) and 39 from Tucupita (rural), in the Orinoco Delta region. Helicobacter pylori was detected by amplification of 16S rRNA, glmM, and ureA genes in 55.0% patients from urban and 87.2% from rural populations. cagA was found positive in 51% and 62% urban and rural patients, respectively. Non-H. pylori Helicobacter species were not detected in the urban population, but was found in 7.7% of patients in the rural study site. Frequency values of the 16S rRNA, glmM, and ureA genes were higher in the rural population. The odds ratio for each gene was 15.18 for 16S rRNA, 2.34 for glmM, 2.89 for ureA, and 1.53 cagA, showing significant differences except for cagA when gene frequency was compared in both populations. These results demonstrate a higher frequency of H. pylori and gastric non-H. pylori Helicobacter infection in a rural mestizo population with low hygienic standards as compared with city dwellers, representing a potential risk for the development of gastroduodenal diseases. PMID:26195456

  12. Helicobacter pylori Infection in Rural and Urban Dyspeptic Patients from Venezuela.

    PubMed

    Contreras, Monica; Fernández-Delgado, Milagro; Reyes, Nelson; García-Amado, María Alexandra; Rojas, Héctor; Michelangeli, Fabian

    2015-10-01

    The goal of this work was to assess the Helicobacter pylori prevalence in a rural mestizo population and compare it to an urban population from Venezuela. The study was performed in gastric juice samples of 71 dyspeptic patients from Caracas (urban) and 39 from Tucupita (rural), in the Orinoco Delta region. Helicobacter pylori was detected by amplification of 16S rRNA, glmM, and ureA genes in 55.0% patients from urban and 87.2% from rural populations. cagA was found positive in 51% and 62% urban and rural patients, respectively. Non-H. pylori Helicobacter species were not detected in the urban population, but was found in 7.7% of patients in the rural study site. Frequency values of the 16S rRNA, glmM, and ureA genes were higher in the rural population. The odds ratio for each gene was 15.18 for 16S rRNA, 2.34 for glmM, 2.89 for ureA, and 1.53 cagA, showing significant differences except for cagA when gene frequency was compared in both populations. These results demonstrate a higher frequency of H. pylori and gastric non-H. pylori Helicobacter infection in a rural mestizo population with low hygienic standards as compared with city dwellers, representing a potential risk for the development of gastroduodenal diseases.

  13. Structural modifications of Helicobacter pylori lipopolysaccharide: an idea for how to live in peace.

    PubMed

    Chmiela, Magdalena; Miszczyk, Eliza; Rudnicka, Karolina

    2014-08-07

    In this review, we discuss the findings and concepts underlying the "persistence mechanisms" of Helicobacter pylori (H. pylori), a spiral-shaped, Gram-negative rod bacterium that was discovered as a gastric pathogen by Marshall and Warren in 1984. H. pylori colonizes the gastric mucosa of nearly half of the human population. Infections appear in early childhood and, if not treated, persist for life. The presence or absence of symptoms and their severity depend on multiple bacterial components, host susceptibility and environmental factors, which allow H. pylori to switch between pathogenicity and commensalism. Many studies have shown that H. pylori components may facilitate the colonization process and the immune response of the host during the course of H. pylori infection. These H. pylori-driven interactions might result from positive or negative modulation. Among the negative immunomodulators, a prominent position is occupied by a vacuolating toxin A (VacA) and cytotoxin-associated gene A (CagA) protein. However, in light of the recent studies that are presented in this review, it is necessary to enrich this panel with H. pylori lipopolysaccharide (LPS). Together with CagA and VacA, LPS suppresses the elimination of H. pylori bacteria from the gastric mucosa by interfering with the activity of innate and adaptive immune cells, diminishing the inflammatory response, and affecting the adaptive T lymphocyte response, thus facilitating the development of chronic infections. The complex strategy of H. pylori bacteria for survival in the gastric mucosa of the host involves both structural modifications of LPS lipid A to diminish its endotoxic properties and the expression and variation of Lewis determinants, arranged in O-specific chains of H. pylori LPS. By mimicking host components, this phenomenon leaves these bacteria "invisible" to immune cells. Together, these mechanisms allow H. pylori to survive and live for many years within their hosts.

  14. Antibiotic resistance among Helicobacter pylori clinical isolates in Lima, Peru

    PubMed Central

    Boehnke, Kevin F; Valdivieso, Manuel; Bussalleu, Alejandro; Sexton, Rachael; Thompson, Kathryn C; Osorio, Soledad; Reyes, Italo Novoa; Crowley, John J; Baker, Laurence H; Xi, Chuanwu

    2017-01-01

    Objectives Gastric carcinoma is the most common cancer and cause of cancer mortality in Peru. Helicobacter pylori, a bacterium that colonizes the human stomach, is a Group 1 carcinogen due to its causal relationship to gastric carcinoma. While eradication of H. pylori can help prevent gastric cancer, characterizing regional antibiotic resistance patterns is necessary to determine targeted treatment for each region. Thus, we examined primary antibiotic resistance in clinical isolates of H. pylori in Lima, Peru. Materials and methods H. pylori strains were isolated from gastric biopsies of patients with histologically proven H. pylori infection. Primary antibiotic resistance among isolates was examined using E-test strips. Isolates were examined for the presence of the cagA pathogenicity island and the vacA m1/m2 alleles via polymerase chain reaction. Results Seventy-six isolates were recovered from gastric biopsies. Clinical isolates showed evidence of antibiotic resistance to 1 (27.6%, n=21/76), 2 (28.9%, n=22/76), or ≥3 antibiotics (40.8%). Of 76 isolates, eight (10.5%) were resistant to amoxicillin and clarithromycin, which are part of the standard triple therapy for H. pylori infection. No trends were seen between the presence of cagA, vacA m1, or vacA m2 and antibiotic resistance. Conclusion The rate of antibiotic resistance among H. pylori isolates in Lima, Peru, is higher than expected and presents cause for concern. To develop more targeted eradication therapies for H. pylori in Peru, more research is needed to better characterize antibiotic resistance among a larger number of clinical isolates prospectively. PMID:28331349

  15. Antiadhesion and anti-inflammation effects of noni (Morinda citrifolia) fruit extracts on AGS cells during Helicobacter pylori infection.

    PubMed

    Huang, Hsin-Lun; Ko, Chien-Hui; Yan, Yeong-Yu; Wang, Chin-Kun

    2014-03-19

    Helicobacter pylori is a human gastric pathogen that adheres to host cells and injects cytotoxin-associated gene A (CagA) to induce interleukin-8 (IL-8), inducible nitric oxide (iNOS), and cyclooxygenase 2 (COX-2). Noni (Morinda citrifolia) is found to possess antibacteria, anti-inflammation, and antioxidation activities, but its effect on H. pylori infection is still unknown. Ethanol and ethyl acetate extracts of noni fruit were used in this study. The inhibitory effect on CagA and H. pylori-induced IL-8, iNOS, and COX-2 were determined. The coculture medium was collected for measuring neutrophil chemotaxis. Both extracts of noni fruit showed weak inhibition on H. pylori. Both ethanol and ethyl acetate extracts provided antiadhesion of H. pylori to AGS cells and down-regulation on the CagA, IL-8, COX-2, and iNOS expressions. Results also indicated both extracts relieved neutrophil chemotaxis. Noni fruit extracts down-regulated inflammatory responses during H. pylori infection, and the phenolic compounds play key role in antiadhesion.

  16. Helicobacter pylori virulence and cancer pathogenesis.

    PubMed

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  17. High Frequency of vacA s1m2 Genotypes Among Helicobacter pylori Isolates From Patients With Gastroduodenal Disorders in Kermanshah, Iran

    PubMed Central

    Pajavand, Hamid; Alvandi, Amirhooshang; Mohajeri, Parviz; Bakhtyari, Somaye; Bashiri, Homayoon; Kalali, Behnam; Gerhard, Markus; Najafi, Farid; Abiri, Ramin

    2015-01-01

    Background: Helicobacter pylori infection and related diseases outcome are mediated by a complex interplay between bacterial, host and environmental factors. Several distinct virulence factors of H. pylori have been shown to be associated with different clinical outcomes. Here we focused on vacA and cagA genotypes of H. pylori strains isolated from patients with gastric disorder. Objectives: The aim of this study was to determine the frequency of two toxins and genotypes of VacA toxin in patients referred to a central hospital in the west of Iran (Imam Reza hospital, Kermanshah) during 2011 - 2012. Patients and Methods: Samples were collected from patients infected with H. pylori. Gastric biopsy specimens from the stomach antrum and corpus were cultured. PCR analysis was performed for genotyping H. pylori vacA and cagA genes. Results: Helicobacter pylori was isolated from 48% (96/200) of patients with gastroduodenal disorders. In 81/96 (84%) cases, the cagA gene was present. Among different genotypes of vacA, two s1m2 and s2m2 genotypes were dominant with frequency of 39.5% and 50%, respectively. The frequency of the s1m1 genotype was 7.2% (7/96), which is much lower than elsewhere. H. pylori isolates with positive results for cagA gene and vacA s1m2 genotypes showed statistically significant correlation with peptic ulcer (s1m2 13/34 [38.2%] P = 0.003). However, isolates of H. pylori infection with cagA gene and vacA s2m2 genotypes were significantly associated with development of gastritis (s2m2 41/42 [97.6%] P = 0.000). Conclusions: About 90% of H. pylori strains potentially contained vacA s2m2 and s1m2 genotypes. Infection with H. pylori strain containing the cagA gene or the vacA s1m1 and s1m2 genotypes was associated with increased incidence of peptic ulcer disease (PUD). PMID:26862378

  18. [Molecular detection and genotypification of Helicobacter pylori in gastric biopsies from symptomatic adult patients in Santa Fe, Argentina].

    PubMed

    Jiménez, Félix; Barbaglia, Yanina; Bucci, Pamela; Tedeschi, Fabián A; Zalazar, Fabián E

    2013-01-01

    Our goals were: a) to detect Helicobacter pylori in gastric biopsies of symptomatic adults by PCR, b) to detect the presence of the cagA gene as well as of the allelic variants of the vacA gene, and c) to correlate genotypes with the endoscopic diagnoses. H. pylori was detected in 81 % (39/48) of patients by nested PCR for hsp60. The presence of cagA was detected in 15/22 of samples and vacA s1 - m1 was the most frequent allelic combination (15/22). Gastritis, the most frequent diagnosis, was associated with genotype cagA+ in 10/13 of patients. In this group, 9/13 showed the allelic variant vacA s1- m1. The variant vacA s2 - m2 was detected in 3/3 of gastritis cases by H. pylori with the cagA- genotype. These results are the first reported in our region and provide data of epidemiological interest.

  19. Helicobacter pylori.

    PubMed Central

    Dunn, B E; Cohen, H; Blaser, M J

    1997-01-01

    Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection. PMID:9336670

  20. Impact of Helicobacter pylori on the healing process of the gastric barrier

    PubMed Central

    Mnich, Eliza; Kowalewicz-Kulbat, Magdalena; Sicińska, Paulina; Hinc, Krzysztof; Obuchowski, Michał; Gajewski, Adrian; Moran, Anthony P; Chmiela, Magdalena

    2016-01-01

    AIM To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover. METHODS In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. RESULTS We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway. CONCLUSION In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier. PMID:27672275

  1. Prevalence of the Helicobacter pylori babA2 gene and correlation with the degree of gastritis in infected Slovenian children.

    PubMed

    Homan, Matjaž; Šterbenc, Anja; Kocjan, Boštjan J; Luzar, Boštjan; Zidar, Nina; Orel, Rok; Poljak, Mario

    2014-10-01

    The aims of our study were to determine the prevalence of the babA2 gene within Helicobacter pylori strains circulating in the Slovenian pediatric population, to further clarify its significance in causing inflammation of gastric mucosa in children and to verify whether cagA, vacA, iceA and babA genes work independently or synergistically in causing gastritis. A total of 163 H. pylori isolates obtained from the same number of children were tested for the presence of cagA, vacA and iceA genes using previously established methods, while the babA2 gene was determined using novel polymerase chain reaction assay targeting a 139-bp fragment of the central region of babA2. The babA2 gene was detected in 47.9% of H. pylori samples. The presence of the babA2 gene was strongly associated with cagA, vacA s1 and vacA m1 genotype. The babA2 status correlated positively with bacterial density score, activity of inflammation and chronic inflammation of gastric mucosa. No significant correlation was found between the babA2 status and the presence of atrophy or intestinal metaplasia. In addition, the activity of gastric inflammation and density score were significantly associated with the coexpression of the cagA, vacA s1, vacA m1 and babA2 genes. The study, which included the largest number of pediatric H. pylori samples to date, confirmed that babA2 gene plays an important role in the pathogenesis of H. pylori gastritis in children. Furthermore, our results suggest that babA2, cagA and vacA s1 and m1 gene products may work synergistically in worsening the inflammation of gastric mucosa.

  2. Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori

    PubMed Central

    Suzuki, Rumiko; Shiota, Seiji; Yamaoka, Yoshio

    2012-01-01

    Helicobacter pylori infection is linked to various gastroduodenal diseases; however, only approximately 20% of infected individuals develop severe diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. Furthermore, the incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors, especially cagA, vacA, and the right end of the cag pathogenicity island. The genotype of the virulence genes is also useful as a tool to track human migration utilizing the high genetic diversity and frequent recombination between different H. pylori strains. Multilocus sequence typing (MLST) analysis using 7 housekeeping genes can also help predict the history of human migrations. Population structure analysis based on MLST has revealed 7 modern population types of H. pylori, which derived from 6 ancestral populations. Interestingly, the incidence of gastric cancer is closely related to the distribution of H. pylori populations. The different incidence of gastric cancer can be partly attributed to the different genotypes of H. pylori circulating in different geographic areas. Although approaches by MLST and virulence factors are effective, these methods focus on a small number of genes and may miss information conveyed by the rest of the genome. Genome-wide analyses using DNA microarray or whole-genome sequencing technology give a broad view on the genome of H. pylori. In particular, next-generation sequencers, which can read DNA sequences in less time and at lower costs than Sanger sequencing, enabled us to efficiently investigate not only the evolution of H. pylori, but also novel virulence factors and genomic changes related to drug resistance. PMID:22197766

  3. Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.

    PubMed

    Ritter, Birgit; Kilian, Petra; Reboll, Marc Rene; Resch, Klaus; DiStefano, Johanna Kay; Frank, Ronald; Beil, Winfried; Nourbakhsh, Mahtab

    2011-02-01

    Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

  4. Host-Interactive Genes in Amerindian Helicobacter pylori Diverge from Their Old World Homologs and Mediate Inflammatory Responses▿ †

    PubMed Central

    Mane, S. P.; Dominguez-Bello, M. G.; Blaser, M. J.; Sobral, B. W.; Hontecillas, R.; Skoneczka, J.; Mohapatra, S. K.; Crasta, O. R.; Evans, C.; Modise, T.; Shallom, S.; Shukla, M.; Varon, C.; Mégraud, F.; Maldonado-Contreras, A. L.; Williams, K. P.; Bassaganya-Riera, J.

    2010-01-01

    Helicobacter pylori is the dominant member of the gastric microbiota and has been associated with an increased risk of gastric cancer and peptic ulcers in adults. H. pylori populations have migrated and diverged with human populations, and health effects vary. Here, we describe the whole genome of the cag-positive strain V225d, cultured from a Venezuelan Piaroa Amerindian subject. To gain insight into the evolution and host adaptation of this bacterium, we undertook comparative H. pylori genomic analyses. A robust multiprotein phylogenetic tree reflects the major human migration out of Africa, across Europe, through Asia, and into the New World, placing Amerindian H. pylori as a particularly close sister group to East Asian H. pylori. In contrast, phylogenetic analysis of the host-interactive genes vacA and cagA shows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci. Despite deletions in CagA EPIYA and CRPIA domains, V225d stimulates interleukin-8 secretion and the hummingbird phenotype in AGS cells. However, following a 33-week passage in the mouse stomach, these phenotypes were lost in isolate V225-RE, which had a 15-kb deletion in the cag pathogenicity island that truncated CagA and eliminated some of the type IV secretion system genes. Thus, the unusual V225d cag architecture was fully functional via conserved elements, but the natural deletion of 13 cag pathogenicity island genes and the truncation of CagA impaired the ability to induce inflammation. PMID:20400544

  5. Comparative Genomics Revealed Multiple Helicobacter pylori Genes Associated with Biofilm Formation In Vitro

    PubMed Central

    Chua, Eng Guan; Tay, Alfred Chin Yen; Peters, Fanny; Marshall, Barry J.; Ho, Bow; Goh, Khean Lee; Vadivelu, Jamuna; Loke, Mun Fai

    2016-01-01

    Background Biofilm formation by Helicobacter pylori may be one of the factors influencing eradication outcome. However, genetic differences between good and poor biofilm forming strains have not been studied. Materials and Methods Biofilm yield of 32 Helicobacter pylori strains (standard strain and 31 clinical strains) were determined by crystal-violet assay and grouped into poor, moderate and good biofilm forming groups. Whole genome sequencing of these 32 clinical strains was performed on the Illumina MiSeq platform. Annotation and comparison of the differences between the genomic sequences were carried out using RAST (Rapid Annotation using Subsystem Technology) and SEED viewer. Genes identified were confirmed using PCR. Results Genes identified to be associated with biofilm formation in H. pylori includes alpha (1,3)-fucosyltransferase, flagellar protein, 3 hypothetical proteins, outer membrane protein and a cag pathogenicity island protein. These genes play a role in bacterial motility, lipopolysaccharide (LPS) synthesis, Lewis antigen synthesis, adhesion and/or the type-IV secretion system (T4SS). Deletion of cagA and cagPAI confirmed that CagA and T4SS were involved in H. pylori biofilm formation. Conclusions Results from this study suggest that biofilm formation in H. pylori might be genetically determined and might be influenced by multiple genes. Good, moderate and poor biofilm forming strain might differ during the initiation of biofilm formation. PMID:27870886

  6. HELICOBACTER PYLORI

    EPA Science Inventory

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  7. Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status

    PubMed Central

    Ma, Seung-Hyun; Jung, Woohyun; Weiderpass, Elisabete; Jang, Jieun; Hwang, Yunji; Ahn, Chunghyun; Ko, Kwang-Pil; Chang, Soung-Hoon; Shin, Hai-Rim; Yoo, Keun-Young; Park, Sue K

    2015-01-01

    Background: Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk. Methods: We selected 949 case–cohort participants from the 18 863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). Results: Relative to non-drinking, heavy drinking (⩾7 times a week), and binge drinking (⩾55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13–10.73) and 3.27-fold (95% CI, 1.01–10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori. Conclusions: Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori. PMID:26379079

  8. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.

  9. Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

    PubMed Central

    Noh, Hye-Ji; Koh, Hong Bum; Kim, Hee-Kyoung; Cho, Hyang Hyun

    2017-01-01

    BACKGROUND/OBJECTIVES Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-1β and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention. PMID:28194260

  10. Study of Helicobacter pylori genotype status in saliva, dental plaques, stool and gastric biopsy samples

    PubMed Central

    Momtaz, Hassan; Souod, Negar; Dabiri, Hossein; Sarshar, Meysam

    2012-01-01

    AIM: To compare genotype of Helicobacter pylori (H. pylori) isolated from saliva, dental plaques, gastric biopsy, and stool of each patient in order to evaluate the mode of transmission of H. pylori infection. METHODS: This cross-sectional descriptive study was performed on 300 antral gastric biopsy, saliva, dental plaque and stool samples which were obtained from patients undergoing upper gastrointestinal tract endoscopy referred to endoscopy centre of Hajar hospital of Shahrekord, Iran from March 2010 to February 2011. Initially, H. pylori strains were identified by rapid urease test (RUT) and polymerase chain reaction (PCR) were applied to determine the presence of H. pylori (ureC) and for genotyping of voculating cytotoxin gene A (vacA) and cytotoxin associated gene A (cagA) genes in each specimen. Finally the data were analyzed by using statistical formulas such as Chi-square and Fisher’s exact tests to find any significant relationship between these genes and patient’s diseases. P < 0.05 was considered statistically significant. RESULTS: Of 300 gastric biopsy samples, 77.66% were confirmed to be H. pylori positive by PCR assay while this bacterium were detected in 10.72% of saliva, 71.67% of stool samples. We were not able to find it in dental plaque specimens. The prevalence of H. pylori was 90.47% among patients with peptic ulcer disease (PUD), 80% among patients with gastric cancer, and 74.13% among patients with none ulcer dyspepsia (NUD) by PCR assay. The evaluation of vacA and cagA genes showed 6 differences between gastric biopsy and saliva specimens and 11 differences between gastric and stool specimens. 94.42% of H. pylori positive specimens were cagA positive and all samples had amplified band both for vacA s and m regions. There was significant relationship between vacA s1a/m1a and PUD diseases (P = 0.04), s2/m2 genotype and NUD diseases (P = 0.05). No statically significant relationship was found between cagA status with clinical outcomes and

  11. From inflammation to gastric cancer: Role of Helicobacter pylori

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying; Aboul-Soud, Mourad A.M.

    2017-01-01

    Gastric cancer is a multifactorial disease and a leading cause of mortality and the risk factors for this include environmental factors and factors that influence host-pathogen interaction and complex interplay between these factors. Gastric adenocarcinomas are of two types, namely intestinal and diffuse type, and Helicobacter pylori (H. pylori) infection has been suspected of being causally linked to the initiation of chronic active gastritis, which leads to adenocarcinoma of the intestinal type. Even though most individuals with H. pylori infection do not show any clinical symptoms, long-term infection leads to inflammation of gastric epithelium and approximately 10% of infected patients develop peptic ulcers and 1–3% of patients develop gastric adenocarcinoma. Among the several mechanisms involved in tumorigenesis, CagA and peptidoglycan of H. pylori, which enter the infected gastric epithelial cells play an important role by triggering oncogenic pathways. Inflammation induced by H. pylori in gastric epithelium, which involves the cyclooxygenase-2/prostaglandin E2 pathway and IL-1β, is also an important factor that triggers chronic active gastritis and adenocarcinoma. H. pylori infection induced oxidative stress and dysregulated E-cadherin/β-catenin/p120 interactions and function also play a critical role in tumorigenesis. Environmental and dietary factors, in particular salt intake, are known to modify the pathogenesis induced by H. pylori. Gastric cancer induced by H. pylori appears to involve several mechanisms, making this mode of tumorigenesis a highly complicated process. Nevertheless, there are many events in this tumorigenesis that remain to be clarified and investigated. PMID:28356927

  12. Association between Helicobacter pylori cagA-related genes and clinical outcomes in Colombia and Japan

    PubMed Central

    2011-01-01

    Background Specific genotypes of several virulence factors of Helicobacter pylori (eg, cagA-positive, vacA s1, oipA "on" and babA-positive) have been reported to be predictors of severe clinical outcomes. Importantly, the presence of these genotypes correlates with each other. We hypothesized that novel virulence genes correlate with the presence of cagA. Therefore, we aimed to find novel candidate virulence genes that correlate with cagA and examined the association of these genes with clinical outcomes in Colombian and Japanese populations. Methods cagA-associated genes were selected based on previous H. pylori genome microarray data. A total of 343 strains (174 from Colombia and 169 from Japan) were examined for the status of cagA, vacA, and candidate genes by polymerase chain reaction and dot blot. Results Microarray data showed that 9 genes were significantly correlated with the presence of cagA. Among the 9 genes, the functions of 4 were known, and we selected these 4 genes as candidate genes (hp0967, jhp0045, jhp0046, and jhp0951). The prevalences of cagA, vacA s1/m1 genotype, and hp0967 were significantly higher in Japan than Colombia, whereas those of jhp0045 and jhp0046 were more prevalent in Colombia than Japan. The prevalences of jhp0045 and jhp0046 in cagA-positive cases of gastric cancer were significantly higher than those from gastritis in Colombia (P = 0.015 and 0.047, respectively). In contrast, the prevalence of 4 candidate genes was independent of clinical outcomes in Japan. Conclusions jhp0045 and jhp0046 might be novel markers for predicting gastric cancer in cagA-positive cases in Colombia, but not in Japan. PMID:22189161

  13. Serological response to Helicobacter pylori infection among Latin American populations with contrasting risks of gastric cancer

    PubMed Central

    Camargo, M. Constanza; Beltran, Mauricio; Conde-Glez, Carlos; Harris, Paul R.; Michel, Angelika; Waterboer, Tim; Flórez, Astrid Carolina; Torres, Javier; Ferreccio, Catterina; Sampson, Joshua N.; Pawlita, Michael; Rabkin, Charles S.

    2015-01-01

    Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti-H. pylori antibodies among populations with at least 2-fold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high- and low-risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead-based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high- and low-risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted-odds ratio, OR: 1.02, p=0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p<0.05) associated with residence in high-risk areas, but ORs were moderate (1.26, 1.42, and 1.41, respectively) and their discriminatory power was low (ROC area under curve <0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori-seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified. PMID:26178251

  14. Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

    PubMed Central

    Melo Barbosa, Hivana Patricia; Martins, Luisa Caricio; dos Santos, Sidney Emanuel Batista; Demachki, Samia; Assumpção, Mônica Baraúna; Aragão, Charliana Damasceno; de Oliveira Corvelo, Tereza Cristina

    2009-01-01

    AIM: To study the association between Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-α polymorphisms, infection by Helicobacter pylori (H pylori) and the development of gastrointestinal diseases. METHODS: Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1β and TNF-α genes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification. RESULTS: A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL-1RN*2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL-RN*2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastric mucosa. CONCLUSION: Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma. PMID:19322919

  15. The Prevalence of Helicobacter pylori Virulence Factors in Bhutan, Vietnam, and Myanmar Is Related to Gastric Cancer Incidence.

    PubMed

    Trang, Tran Thi Huyen; Shiota, Seiji; Matsuda, Miyuki; Binh, Tran Thanh; Suzuki, Rumiko; Vilaichone, Ratha-korn; Mahachai, Varocha; Tshering, Lotay; Dung, Ho D Q; Uchida, Tomohisa; Matsunari, Osamu; Myint, Thein; Khien, Vu Van; Yamaoka, Yoshio

    2015-01-01

    Gastric cancer is a significant health problem in Asia. Although the prevalence of Helicobacter pylori infection is similar in Bhutan, Vietnam, and Myanmar, the incidence of gastric cancer is highest in Bhutan, followed by Vietnam and Myanmar. We hypothesized that H. pylori virulence factors contribute to the differences. The status of cagA, vacA, jhp0562, and β-(1,3)galT(jhp0563) was examined in 371 H. pylori-infected patients from Bhutan, Vietnam, and Myanmar. Each virulence factor could not explain the difference of the incidence of gastric cancer. However, the prevalence of quadruple-positive for cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative was significantly higher in Bhutan than in Vietnam and Myanmar and correlated with gastric cancer incidence. Moreover, gastritis-staging scores measured by histology of gastric mucosa were significantly higher in quadruple-positive strains. We suggest that the cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative genotype may play a role in the development of gastric cancer.

  16. Cost-effectiveness of screening and treating Helicobacter pylori for gastric cancer prevention.

    PubMed

    Lansdorp-Vogelaar, Iris; Sharp, Linda

    2013-12-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. A meta-analysis of seven randomized controlled trials concluded that Helicobacter pylori eradication reduces gastric cancer incidence by 35%. Current consensus is that H. pylori screening and treatment is cost-effective only in high-risk populations. This paper provides an up-to-date overview of the evidence for cost-effectiveness of H. pylori screening and treatment in different population settings and risk levels for H. pylori infection. Ten unique cost-effectiveness or cost-utility analyses were identified. All found that screening for H. pylori to prevent gastric cancer in the general population costs less than $50,000 per LYG. This finding was robust for differences in H. pylori prevalence, gender and ethnicity. Based on limited evidence, re-treatment (for treatment failure), repeated screening, limiting screening and treatment to those with the CagA phenotype, or universal treatment, does not appear to be cost-effective. However, most included studies failed to consider both the broader benefits as well as the adverse effects of widespread use of antibiotics for H. pylori.

  17. Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests.

    PubMed

    Miftahussurur, M; Shiota, S; Suzuki, R; Matsuda, M; Uchida, T; Kido, Y; Kawamoto, F; Maimunah, U; Adi, P; Rezkitha, Y; Nasronudin; Nusi, I; Yamaoka, Y

    2015-04-01

    SUMMARY The prevalence of Helicobacter pylori infection in Indonesia is controversial. We examined the H. pylori infection rate in 78 patients in a hospital in Surabaya using five different tests, including culture, histology, immunohistochemistry, rapid urease test, and urine antibody test. Furthermore, we analysed virulence factors in H. pylori strains from Indonesia. The H. pylori infection rate was only 11.5% in all patients studied, and 2.3% of Javanese patients and 18.0% of Chinese patients were infected (P = 0.01). Although severe gastritis was not observed, activity and inflammation were significantly higher in patients positive for H. pylori than in patients negative for H. pylori. Among genotypes identified from five isolated strains, cagA was found in four; two were vacA s1m1. All cagA-positive strains were oipA 'on' and iceA1 positive. We confirmed both a low H. pylori infection rate and a low prevalence of precancerous lesions in dyspeptic patients in a Surabaya hospital, which may contribute to the low incidence of gastric cancer in Indonesia.

  18. Salt intake and type of intestinal metaplasia in Helicobacter pylori-infected Portuguese men.

    PubMed

    Pintalhao, Mariana; Dias-Neto, Marina; Peleteiro, Bárbara; Lopes, Carla; Figueiredo, Céu; David, Leonor; Lunet, Nuno

    2010-01-01

    The relation between salt intake and intestinal metaplasia (IM) types and the potential interaction with H. pylori virulence are poorly understood and may contribute to further understand gastric carcinogenesis. We quantified the association between dietary salt exposure and complete, incomplete, and mixed IM, taking into account the potential effect modification according to the virulence of H. pylori infecting strains. H. pylori-infected male volunteers (n = 233) underwent an upper digestive endoscopy and completed questionnaires comprising different measures of salt exposure (main food items/groups contributing to dietary salt intake, estimated dietary sodium intake, visual analogical scale for salt intake, preference for salty/salted foods). A histological diagnosis was assigned based on the most severe lesion observed. H. pylori virulence was assessed by characterizing vacA and cagA genes. Odds ratios were estimated through age- and education-adjusted logistic regression models. The risk of IM was not significantly increased in H. pylori infected subjects with higher levels of salt consumption. The lack of association was consistent across measures of salt exposure, categories of H. pylori virulence, and types of IM. In conclusion, in this H. pylori positive population, salt intake did not increase the risk of any IM type, regardless of the virulence of the infecting strains.

  19. Relationship between Helicobacter pylori virulence factors and regulatory cytokines as predictors of clinical outcome

    PubMed Central

    Serrano, Carolina; Diaz, Maria Ines; Valdivia, Alejandra; Godoy, Alex; Peña, Alfredo; Rollan, Antonio; Kirberg, Arturo; Hebel, Eduardo; Fierro, Jaqueline; Klapp, Gerardo; Venegas, Alejandro; Harris, Paul R.

    2013-01-01

    H. pylori infection is highly prevalent in Chile (73%). Usually a minority of infected patients develops complications such as ulcers and gastric cancer that have been associated with the presence of virulence factors (cagA, vacA) and host T helper response (Th1/Th2). Our aim was to evaluate the relationship between strain virulence and host immune response, using a multiple regression approach for the development of a model based on data collected from H. pylori infected patients in Chile. We analyzed levels of selected cytokines determined by ELISA (IL-12, IL-10, IFN-γ and IL-4) and the presence of cagA and vacA alleles polymorphisms determined by PCR in antral biopsies of 41 patients referred to endoscopy. By multiple regression analysis we established a correlation between bacterial and host factors using clinical outcome (gastritis and duodenal ulcer) as dependent variables. The selected model was described by: clinical outcome = 0.867491 (cagA) + 0.0131847 (IL-12/IL-10) + 0.0103503 (IFN-γ/IL-4) and it was able to explain over 90% of clinical outcomes observations (R2=96.4). This model considers that clinical outcomes are better explained by the interaction of host immune factors and strain virulence as a complex and interdependent mechanism. PMID:17336120

  20. Determination of Helicobacter pylori virulence by analysis of the cag pathogenicity island isolated from Iranian population

    PubMed Central

    Baghaei, Kaveh; Shokrzadeh, Leila; Jafari, Fereshteh; Dabiri, Hossein; Yamaoka, Yoshio; Bolfion, Mehdi; Zojaji, Homayon; Aslani, Mehdi; Zali, Mohammad Reza

    2009-01-01

    Background The cag pathogenicity island (PAI), which can divide into two parts: cagI and cagII, is the most well-known virulence factor of Helicobacter pylori. Aims We investigated the association between genetic variations within the cag PAI (cagA and cagE in the cagI and cagT in the cagII) and clinical outcomes in Iranian population. Subjects A total of 231 patients including 182 patients with gastritis, 41 with peptic ulcer and 8 with gastric cancer. Methods The presences of the cagA, cagE and cagT genes were measured by polymerase chain reaction and the results were compared with clinical outcomes and gastric histology. Results The cagA, cagE and cagT genes were found in 154 (66.7%), 90 (39.0%) and 70 (30.3%) of clinical isolates. At least 144 (62.3%) strains possessed partially deleted cag PAI (e.g., 69 [29.9%] strains were cagA-positive, but cagE and cagT-negative). Conclusion The simple gene as well as the combination of the genes in the cag PAI appeared not to be useful markers to predict H. pylori-related diseases in Iranian population. The genomic sequences of the cag PAI in Iranian strains might be considerably different from those in other geographic locations. PMID:19261552

  1. An association between sudden infant death syndrome (SIDS) and Helicobacter pylori infection

    PubMed Central

    Kerr, J; Al-Khattaf, A; Barson, A; Burnie, J

    2000-01-01

    BACKGROUND—Helicobacter pylori has recently been detected in the stomach and trachea of cases of sudden infant death syndrome (SIDS) and proposed as a cause of SIDS.
AIMS—To establish the incidence of H pylori in the stomach, trachea, and lung of cases of SIDS and controls.
METHODS—Stomach, trachea, and lung tissues from 32 cases of SIDS and eight control cases were examined retrospectively. Diagnosis of SIDS was based on established criteria. Controls were defined by death within 1 year of age and an identifiable cause of death. Tissues were examined histologically for the presence of bacteria. Extracted DNA from these tissues was tested for H pylori ureC and cagA sequences by nested polymerase chain reaction and amplicons detected by enzyme linked immunosorbent assay (ELISA). The cut off for each ELISA for each of the tissue types was taken as the mean optical density plus two times the standard deviation of a range of negative controls.
RESULTS—Ages of SIDS cases ranged from 2 to 28 weeks. Ages of controls ranged from 3 to 44 weeks. For the ureC gene, 25 SIDS cases were positive in one or more tissues compared with one of the controls. For the cagA gene, 25 SIDS cases were positive in one or more tissues compared with one of the controls.
CONCLUSIONS—There is a highly significant association between H pylori ureC and cagA genes in the stomach, trachea, and lung of cases of SIDS when compared with controls.

 PMID:11040154

  2. Evidence for ethnic tropism of Helicobacter pylori.

    PubMed Central

    Campbell, S; Fraser, A; Holliss, B; Schmid, J; O'Toole, P W

    1997-01-01

    Helicobacter pylori infection in humans is linked to gastritis, gastric and duodenal ulcers, and gastric cancer. Peptic ulcer disease, as distinct from chronic asymptomatic infection, is strongly associated with expression of bacterial virulence markers, including a major antigen, CagA, and the vacuolating cytotoxin VacA. We have previously described significant differences in colonization rates, independent of socioeconomic status, among ethnic groups in New Zealand. To evaluate relative risks for peptic ulcer disease, we examined the frequency of two virulence markers in H. pylori strains infecting these ethnic groups. Although these markers occurred significantly more frequently in strains isolated from Polynesians than in strains from Europeans, this frequency was not reflected in the incidence of peptic ulcer disease in the two groups. DNA fingerprinting of the urease gene showed that Polynesians are more frequently infected by a group of strains which are genetically distinct from those affecting European New Zealanders. Our data suggest that separate bacterial lineages may have evolved in parallel with race-specific specialization. PMID:9284141

  3. The design of vaccines against Helicobacter pylori and their development.

    PubMed

    Del Giudice, G; Covacci, A; Telford, J L; Montecucco, C; Rappuoli, R

    2001-01-01

    Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium that infects the stomach of more than 50% of the human population worldwide. It is mostly acquired during childhood and, if not treated, persists chronically, causing chronic gastritis, peptic ulcer disease, and in some individuals, gastric adenocarcinoma and gastric B cell lymphoma. The current therapy, based on the use of a proton-pump inhibitor and antibiotics, is efficacious but faces problems such as patient compliance, antibiotic resistance, and possible recurrence of infection. The development of an efficacious vaccine against H. pylori would thus offer several advantages. Various approaches have been followed in the development of vaccines against H. pylori, most of which have been based on the use of selected antigens known to be involved in the pathogenesis of the infection, such as urease, the vacuolating cytotoxin (VacA), the cytotoxin-associated antigen (CagA), the neutrophil-activating protein (NAP), and others, and intended to confer protection prophylactically and/or therapeutically in animal models of infection. However, very little is known of the natural history of H. pylori infection and of the kinetics of the induced immune responses. Several lines of evidence suggest that H. pylori infection is accompanied by a pronounced Th1-type CD4(+) T cell response. It appears, however, that after immunization, the antigen-specific response is predominantly polarized toward a Th2-type response, with production of cytokines that can inhibit the activation of Th1 cells and of macrophages, and the production of proinflammatory cytokines. The exact effector mechanisms of protection induced after immunization are still poorly understood. The next couple of years will be crucial for the development of vaccines against H. pylori. Several trials are foreseen in humans, and expectations are that most of the questions being asked now on the host-microbe interactions will be answered.

  4. Helicobacter pylori infection in women with Hashimoto thyroiditis

    PubMed Central

    Shmuely, Haim; Shimon, Ilan; Gitter, Limor Azulay

    2016-01-01

    Abstract An association between Helicobacter pylori (H pylori) infection as environmental risk factors for Hashimoto thyroiditis (HT) has been reported. We investigated this hypothesis in women in which HT is more common. Serum immunoglobulin G antibodies against H pylori (enzyme-linked immunosorbent assay), CagA protein (Western blot assay), circulating antibodies to thyroid antigens, mainly thyroperoxidase (TPOAbs) and thyroglobulin (TgAbs), were tested in 101 females with HT and 111 non-HT control women without a history of autoimmune disease. Thyroid function, socioeconomic status at childhood, and family history of thyroid malfunction were also studied. Forty-seven HT women (46.5%) tested seropositive for H pylori versus 48 controls (43.2%; P = 0.63). The prevalence of anti-CagA antibodies was 21.3% in HT-infected patients and 31.2% in infected controls (P = 0.352). Women with HT were older than the controls at a significance level of 0.03, and higher prevalence of hypothyroidism (69% vs 13.5%, respectively) and family history of thyroid malfunction (59% vs 34%, respectively) (P < 0.001 in both). Body mass index, diaphragmatic hernia, peptic ulcer, heartburn, use of proton pump inhibitors, childhood socioeconomic background, and crowding index showed no significant difference between HT-positive or negative individuals. Multivariate analysis demonstrated that H pylori seropositivity was not associated with HT (odds ratio 1.15, 95% confidence interval 0.57–1.83, P = 0.95) and that family thyroid malfunction was independently associated with an increased risk of HT (odds ratio 3.39, 95% confidence interval 1.86–6.18, P < 0.001). No association was found between H pylori infection and HT in women. Family history of thyroid malfunction is a risk factor for HT. PMID:27442635

  5. [Susceptibility of 36 Helicobacter pylori clinical isolates to four first-line antibiotics and virulence factors].

    PubMed

    Díaz-Reganon, J; Alarcón, T; Domingo, D; López-Brea, M

    2006-03-01

    Helicobacter pylori possess various virulence factors, including cagA and vacA genes, that are associated with more aggressive symptoms such as bleed-ing ulcer and gastric cancer. Although there are different treatment regimens, there is still a failure rate of up to 20% due to antibiotic resistance, among other causes. In our country resistance to metronidazole and clarithromycin is increasing, especially in children, although they are still susceptible to amoxicillin and tetracycline. In order to determine the susceptibility pattern to these antibiotics 36 H. pylori clinical isolates were studied. MIC was determined by agar diffusion and agar dilution, and vacA and cagA genes were detected by conventional PCR. All isolates were susceptible to amoxicillin and tetracycline. Resistance to metronidazole by diffusion or dilution tests was 35.7% and 36.1%, respectively, and to clarithromycin, 21.4% and 22.3%, respectively. There was one strain that showed intermediate resistance to clarithromycin (MIC 0.38 mg/l), using agar diffusion, and that was included among the resistant strains. Three discrepancies were observed between the diffusion and dilution methods. The vacA s1 allele was detected in 17.2% of the strains, and vacA s2 in 82.8%; 51.7% of the total were cagA+. In conclusion, all strains tested in our study were susceptible to amoxicillin and tetracycline, allowing them to be considered as first-line antibiotics, while clarithromycin and metronidazole maintain a slight increase in their resistance level. The cagA+ strains were detected in expected quantities, while the s1 allele of the vacA gene was detected in lower quantities.

  6. Helicobacter pylori inhibits the cleavage of TRAF1 via a CagA-dependent mechanism

    PubMed Central

    Wan, Xiu-Kun; Yuan, Sheng-Ling; Wang, Yan-Chun; Tao, Hao-Xia; Jiang, Wei; Guan, Zhang-Yan; Cao, Cheng; Liu, Chun-Jie

    2016-01-01

    AIM To study the impact on cleavage of tumor necrosis factor receptor-associated factor 1 (TRAF1) regulated by Helicobacter pylori (H. pylori). METHODS Cleavage of TRAF1 was detected by western blotting in the human gastric cancer cell line AGS following treatment with an apoptosis inducer. Cleavage of TRAF1 mediated by caspase was examined in vitro using specific caspase inhibitors. The effect of the COOH-terminal TRAF1 fragment on gastric cell apoptosis during H. pylori infection was measured using flow cytometry. The impact of H. pylori infection on TRAF1 cleavage was detected in the presence of apoptosis inducer. The roles of H. pylori virulence factors that may regulate TRAF1 cleavage were analyzed using isogenic cagA-, vacA- and cagE-null mutants. RESULTS TRAF1 was found to be cleaved in AGS cells treated with the apoptosis inducer, and caspase-8 was the major caspase involved in the cleavage of TRAF1. The COOH-terminal TRAF1 fragment significantly induced cell apoptosis (P < 0.05) as well as promoted H. pylori-induced cell apoptosis (P < 0.05). H. pylori infection was found to significantly inhibit the cleavage of TRAF1 and to inhibit the activation of caspase-8 in the presence of the apoptosis inducer at specific infection times and different cell/bacteria ratios. We also found that the effects of cagE- and cagA-null mutants on the inhibition of TRAF1 cleavage and activation of caspase-8 were significantly attenuated, compared with wild-type H. pylori, in the presence of the apoptosis inducer, showing that the virulence factor CagA was mainly involved in the inhibition of TRAF1 cleavage. CONCLUSION H. pylori infection significantly inhibits the cleavage of TRAF1 via a CagA-dependent mechanism, which would increase the relative amounts of full-length TRAF1 and exert an antiapoptotic effect on H. pylori-infected cells. PMID:28082808

  7. Helicobacter pylori outer membrane protein Q allele distribution is associated with distinct pathologies in Pakistan.

    PubMed

    Yakoob, Javed; Abbas, Zaigham; Khan, Rustam; Salim, Saima Azhar; Awan, Safia; Abrar, Ambar; Jafri, Wasim

    2016-01-01

    Helicobacter pylori (H. pylori) strains expressing outer membrane protein Q (HopQ) promote adherence to the gastric epithelial cell. We characterized HopQ alleles in relation to H. pylori-related disease, histology and virulence markers. Gastric biopsies were obtained at esophagogastroduodenoscopy from patients with upper gastrointestinal symptoms. H. pylori culture, histology and polymerase chain reaction (PCR) for HopQ types, cagA, cagA-promoter and vacA alleles were performed. DNA extracted was used for PCR. Sequencing of PCR products of HopQ types 1 and 2 was followed by BLAST query. We examined 241 H. pylori isolates. HopQ type 1 was positive in 70 (29%) isolates, type 2 in 60 (25%) isolates, while both type 1 and type 2 in 111 (46%) H. pylori isolates, respectively. Nonulcer dyspepsia (NUD) was associated with HopQ type 2 in 48 (41%) isolates, while gastric carcinoma (GC) in 37 (53%) (P<0.001) with type 1 isolates. Gastric ulcers (GU) were 39 (46%) (P<0.001) in H. pylori infection with multiple HopQ alleles compared to 6 (23%) in HopQ type 1. Multivariate analysis demonstrated that multiple HopQ alleles were associated with GU OR 2.9 (1.07-7.8) (P=0.03). HopQ type 1 was associated with cagA 58 (84%) (P<0.001) and cagA-promoter 58 (83%) (P<0.001) compared to 14 (23%) and 17 (28%) respectively, in type 2. VacAs1a was associated with HopQ type 1 in 59 (84%) isolates compared to HopQ type 2 in 35 (58%) (P=0.002) isolates. VacAm1 was associated with HopQ type 1 in 53 (76%) isolates compared to HopQ type 2 in 32 (53%) (P=0.004) isolates. H. pylori infection with multiple HopQ alleles was predominant. H. pylori infection with single HopQ type 1 was associated with GC in the presence of other H. pylori virulence markers.

  8. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

    PubMed

    Lewinska, Anna; Wnuk, Maciej

    2017-04-01

    Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

  9. Latest insights into the effects of Helicobacter pylori infection on gastric carcinogenesis

    PubMed Central

    Murakami, Kazunari; Kodama, Masaaki; Fujioka, Toshio

    2006-01-01

    There appears to be the strong association between Helicobacter pylori (H pylori) and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between H pylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pylori-associated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bone-marrow derived stem cells (BMDC) as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond. PMID:16718758

  10. Mixed Infections of Helicobacter pylori Isolated from Patients with Gastrointestinal Diseases in Taiwan

    PubMed Central

    Huang, Ju-Chun; Chiang-Ni, Chuan; Li, Ju-Pi; Wu, Lii-Tzu; Wu, Hua-Shan; Sun, Yu-Chen; Lin, Mei-Ling; Lee, Ju-Fang

    2016-01-01

    Background. Persistent Helicobacter pylori infection may induce several upper gastrointestinal diseases. Two major virulence factors of H. pylori, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), are thought to be associated with the severity of disease progression. The distribution of vacA and cag-pathogenicity island (cag-PAI) alleles varies in H. pylori isolated from patients in different geographic regions. Aim. To assess the association between mixed infection of H. pylori clinical isolates from Taiwanese patients and the severity of gastrointestinal diseases. Methods. A total of 70 patients were enrolled in this study. Six distinct and well-separated colonies were isolated from each patient and 420 colonies were analyzed to determine the genotypes of virulence genes. Results. The prevalence of mixed infections of all H. pylori-infected patients was 28.6% (20/70). The rate of mixed infections in patients with duodenal ulcer (47.6%) was much higher than that with other gastrointestinal diseases (P < 0.05). Conclusions. H. pylori mixed infections show high genetic diversity that may enhance bacterial adaptation to the hostile environment of the stomach and contribute to disease development. PMID:27738429

  11. Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study.

    PubMed

    Huang, Jiaqi; Zagai, Ulrika; Hallmans, Göran; Nyrén, Olof; Engstrand, Lars; Stolzenberg-Solomon, Rachael; Duell, Eric J; Overvad, Kim; Katzke, Verena A; Kaaks, Rudolf; Jenab, Mazda; Park, Jin Young; Murillo, Raul; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Bradbury, Kathryn E; Riboli, Elio; Aune, Dagfinn; Tsilidis, Konstantinos K; Capellá, Gabriel; Agudo, Antonio; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Weiderpass, Elisabete; Tjønneland, Anne; Olsen, Anja; Martínez, Begoña; Redondo-Sanchez, Daniel; Chirlaque, Maria-Dolores; Hm Peeters, Petra; Regnér, Sara; Lindkvist, Björn; Naccarati, Alessio; Ardanaz, Eva; Larrañaga, Nerea; Boutron-Ruault, Marie-Christine; Rebours, Vinciane; Barré, Amélie; Bueno-de-Mesquita, H B As; Ye, Weimin

    2017-04-15

    The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.

  12. Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer.

    PubMed

    Yong, Xin; Tang, Bo; Xiao, Yu-Feng; Xie, Rui; Qin, Yong; Luo, Gang; Hu, Chang-Jiang; Dong, Hui; Yang, Shi-Ming

    2016-05-01

    Helicobacter pylori (H. pylori) infection is considered a major risk factor for gastric cancer. CagA behaves as a major bacterial oncoprotein playing a key role in H. pylori-induced tumorigenesis. Cancer stem cells (CSCs) are believed to possess the ability to initiate tumorigenesis and promote progression. Although studies have suggested that cancer cells can exhibit CSC-like properties in the tumor microenvironment, it remains unclear whether H. pylori infection could induce the emergence of CSC-like properties in gastric cancer cells and, the underlying mechanism. Here, gastric cancer cells were co-cultured with a CagA-positive H. pylori strain or a CagA isogenic mutant strain. We found that H. pylori-infected gastric cancer cells exhibited CSC-like properties, including an increased expression of CSC specific surface markers CD44 and Lgr5, as well as that of Nanog, Oct4 and c-myc, which are known pluripotency genes, and an increased capacity for self-renewal, whereas these properties were not observed in the CagA isogenic mutant strain-infected cells. Further studies revealed that H. pylori activated Wnt/β-catenin signaling pathway in a CagA-dependent manner and that the activation of this pathway was dependent upon CagA-positive H. pylori-mediated phosphorylation of β-catenin at the C-terminal Ser675 and Ser552 residues in a c-met- and/or Akt-dependent manner. We further demonstrated that this activation was responsible for H. pylori-induced CSC-like properties. Moreover, we found the promoter activity of Nanog and Oct4 were upregulated, and β-catenin was observed to bind to these promoters during H. pylori infection, while a Wnt/β-catenin inhibitor suppressed promoter activity and binding. Taken together, these results suggest that H. pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote CSC-like properties in gastric cancer cells.

  13. A pilot study of Helicobacter pylori genotypes and cytokine gene polymorphisms in reflux oesophagitis and peptic ulcer disease.

    PubMed

    Akdogan, R A; Ozgur, O; Gucuyeter, S; Kaklikkaya, N; Cobanoglu, U; Aydin, F

    2014-01-01

    Helicobacter pylori causes various diseases such as chronic gastritis, peptic ulcer and gastric cancer. While majority of the people infected with H. pylori is asymptomatic, 15-20 % of them develop such diseases. The main factors, which determine the development of H. pylori related diseases might be bacterial virulence, host genetic and environmental factors.The aim of this study was to reveal the factors that play a role in the disease development in patients with reflux esophagitis and peptic ulcer, infected with Helicobacter pylori. Environmental factors such as medical agents, smoking and body mass index were evaluated. The factors specific to bacteria such as vacA, CagA, babA and iceA virulence genotypes and the host factors such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, interferon-γ, TNF-α, ve TGF-β1 gene polymorphisms were compared between the two groups.H. pylori infected twenty five patients with reflux esophagitis and peptic ulcer were enrolled in the study. There was no statistical difference between the two groups regarding environmental factors. IL-2 -330T +166T (p=0.037) and IL10 -1082A; -819C (p=0.049) gene polymorphisms were significantly more common in the group of patients with peptic ulcer compared to the group with reflux esophagitis. In both groups of patients, either with reflux esophagitis or peptic ulcer, multiple H. pylori virulence genotypes (cagA, vacA, babA) (mean values 74 %, 78 %, 54 % respectively) were observed.In this study, we revealed that cytokine gene polymorphisms may play a role in the development peptic ulcer while H. pylori virulence genotypes seem to be crucial for the development of associated diseases (Tab. 4, Ref. 51).

  14. Caveolin-1 Protects B6129 Mice against Helicobacter pylori Gastritis

    PubMed Central

    Hitkova, Ivana; Yuan, Gang; Anderl, Florian; Gerhard, Markus; Kirchner, Thomas; Reu, Simone; Röcken, Christoph; Schäfer, Claus; Schmid, Roland M.; Vogelmann, Roger; Ebert, Matthias P. A.; Burgermeister, Elke

    2013-01-01

    Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies (“humming bird”) compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells. PMID:23592983

  15. High prevalence of clarithromycin-resistant Helicobacter pylori strains and risk factors associated with resistance in Madrid, Spain.

    PubMed

    Agudo, Sonia; Pérez-Pérez, Guillermo; Alarcón, Teresa; López-Brea, Manuel

    2010-10-01

    Clarithromycin is one of the antibiotics used for the treatment of Helicobacter pylori infections, and clarithromycin resistance is the most important factor when it comes to predicting eradication failure. The present study analyzed H. pylori isolates for the presence of 23S rRNA gene mutations and determined the risk factors associated with resistance among H. pylori isolates collected in Madrid, Spain, in 2008. We studied 118 H. pylori strains isolated from the same number of patients. A total of 76.3% of the patients were born in Spain, 52.7% were children, 20.3% had previously been treated, and 66.1% were female. Clarithromycin resistance was determined by Etest. H. pylori strains were considered resistant if the MIC was ≥1 mg/liter. DNA extraction was carried out by use of the NucliSens easyMAG platform with NucliSens magnetic extraction reagents (bioMérieux). The DNA sequences of the 23S rRNA genes of clarithromycin-resistant and -sensitive strains were determined to identify specific point mutations. The vacA genotype and cagA status were determined by PCR. We found that 42 (35.6%) strains were resistant to clarithromycin by Etest. Etest results were confirmed by detection of the presence of point mutations in 34 (88.1%) of these strains. Eight H. pylori strains were resistant to clarithromycin by Etest but did not have a point mutation in the 23S rRNA gene. Mutation at A2143G was found in 85.3% of the strains, mutation at A2142G in 8.8%, and mutation at T2182C in 5.9%. Dual mutations were found in 8.8% of the strains. H. pylori clarithromycin-resistant strains were strongly associated with pediatric patients, with patients born in Spain, and with patients who had previously been treated (P ≤ 0.02). In addition, H. pylori strains resistant to clarithromycin more frequently presented the vacA s2/m2 genotype and were more likely to be cagA negative than susceptible strains (39.1% and 11.2%, respectively; P value < 0.001). We concluded that, in the

  16. Helicobacter pylori lipopolysaccharide is synthesized via a novel pathway with an evolutionary connection to protein N-glycosylation.

    PubMed

    Hug, Isabelle; Couturier, Marc R; Rooker, Michelle M; Taylor, Diane E; Stein, Markus; Feldman, Mario F

    2010-03-19

    Lipopolysaccharide (LPS) is a major component on the surface of Gram negative bacteria and is composed of lipid A-core and the O antigen polysaccharide. O polysaccharides of the gastric pathogen Helicobacter pylori contain Lewis antigens, mimicking glycan structures produced by human cells. The interaction of Lewis antigens with human dendritic cells induces a modulation of the immune response, contributing to the H. pylori virulence. The amount and position of Lewis antigens in the LPS varies among H. pylori isolates, indicating an adaptation to the host. In contrast to most bacteria, the genes for H. pylori O antigen biosynthesis are spread throughout the chromosome, which likely contributed to the fact that the LPS assembly pathway remained uncharacterized. In this study, two enzymes typically involved in LPS biosynthesis were found encoded in the H. pylori genome; the initiating glycosyltransferase WecA, and the O antigen ligase WaaL. Fluorescence microscopy and analysis of LPS from H. pylori mutants revealed that WecA and WaaL are involved in LPS production. Activity of WecA was additionally demonstrated with complementation experiments in Escherichia coli. WaaL ligase activity was shown in vitro. Analysis of the H. pylori genome failed to detect a flippase typically involved in O antigen synthesis. Instead, we identified a homolog of a flippase involved in protein N-glycosylation in other bacteria, although this pathway is not present in H. pylori. This flippase named Wzk was essential for O antigen display in H. pylori and was able to transport various glycans in E. coli. Whereas the O antigen mutants showed normal swimming motility and injection of the toxin CagA into host cells, the uptake of DNA seemed to be affected. We conclude that H. pylori uses a novel LPS biosynthetic pathway, evolutionarily connected to bacterial protein N-glycosylation.

  17. Novel epidermal growth factor receptor pathway mediates release of human β-defensin 3 from Helicobacter pylori-infected gastric epithelial cells.

    PubMed

    Muhammad, Jibran S; Zaidi, Syed F; Zhou, Yue; Sakurai, Hiroaki; Sugiyama, Toshiro

    2016-04-01

    Persistent Helicobacter pylori (H. pylori) infection in hostile gastric mucosa can result in gastric diseases. Helicobacter pylori induces to express antimicrobial peptides from gastric epithelial cells, especially human β-defensin 3 (hBD3), as an innate immune response, and this expression of hBD3 is mediated by epidermal growth factor receptor (EGFR) activation. In this study, we found that phosphorylation of a serine residue of EGFR via transforming growth factor β-activated kinase-1 (TAK1), and subsequent p38α activation is essential for H. pylori-induced hBD3 release from gastric epithelial cells. We showed that this pathway was dependent on H. pylori type IV secretion system and was independent of H. pylori-derived CagA or peptidoglycan. H. pylori infection induced phosphorylation of serine residue of EGFR, and this phosphorylation was followed by internalization of EGFR; consequently, hBD3 was released at an early phase of the infection. In the presence of TAK1 or p38α inhibitors, synthesis of hBD3 was completely inhibited. Similar results were observed in EGFR-, TAK1- or p38α-knockdown cells. However, NOD1 knockdown in gastric epithelial cells did not inhibit hBD3 induction. Our study has firstly demonstrated that this novel EGFR activating pathway functioned to induce hBD3 at an early phase of H. pylori infection.

  18. Helicobacter pylori with East Asian-type cagPAI genes is more virulent than strains with Western-type in some cagPAI genes.

    PubMed

    Yuan, Xiao-Yan; Yan, Jin-Jun; Yang, Ya-Chao; Wu, Chun-Mei; Hu, Yan; Geng, Jian-Li

    2016-12-22

    The severity of Helicobacter pylori-related disease is correlated with the presence and integrity of a cag pathogenicity island (cagPAI). cagPAI genotype may have a modifying effect on the pathogenic potential of the infecting strain. After analyzing the sequences of cagPAI genes, some strains with the East Asian-type cagPAI genes were selected for further analysis to examine the association between the diversity of the cagPAI genes and the virulence of H. pylori. The results showed that gastric mucosal inflammatory cell infiltration was significantly higher in patients with East Asian-type cagPAI genes H. pylori strain compared with mosaicism cagPAI genes H. pylori strain (p<0.05). H. pylori strains with the East Asian-type cagPAI genes were closely associated with IL-8 secretion in vitro and in vivo compared with H. pylori strains with the mosaicism cagPAI genes (p<0.01). H. pylori strains with East Asian-type cagPAI genes are able to strongly translocate CagA to host cells. These results suggest that H. pylori strains with East Asian-type cagPAI genes are more virulent than the strains of cagPAI gene/genes that are Western type.

  19. Helicobacter Pylori Infections

    MedlinePlus

    Helicobacter pylori (H. pylori) is a type of bacteria that causes infection in the stomach. It is found in about two-thirds of ... or stool to see if it contains H. pylori. The best treatment is a combination of antibiotics ...

  20. Study of the oipA genetic diversity and EPIYA motif patterns in cagA-positive Helicobacter pylori strains from Venezuelan patients with chronic gastritis.

    PubMed

    Torres, Keila; Valderrama, Elvis; Sayegh, Marjorie; Ramírez, José Luis; Chiurillo, Miguel Angel

    2014-11-01

    CagA and OipA are involved, among other virulence factors, in the ability of Helicobacter pylori to colonize the gastric mucosa and to modulate the host environment during the establishment of chronic infection. The number and type of EPIYA phosphorylation motifs and the presence and functional status of oipA have been involved in the induction of cellular transformations playing an important role in the development of H. pylori associated gastric diseases. This work determined the prevalence of the oipA virulence factor and EPIYA motif patterns in cagA-positive H. pylori gastric biopsies from chronic gastritis patients from the Central-Western region of Venezuela. DNA was extracted directly from gastric biopsies collected by upper endoscopy from 113 patients. The EPIYA motif genotyping and oipA gene functional status was determined by PCR and sequencing. Phylogenetic analysis with the 3' variable region of cagA sequences was performed. Only Western-type EPIYA variants were detected: ABC (68.14%), ABCC (29.20%) and ABCCC (2.66%). High prevalence of strains with the oipA gene (93.8%) and its functional status "ON" (83%) was observed. No significant association between EPIYA motif patterns or oipA functional status with the histological changes in the gastric mucosa was found. Our study demonstrated the absolute predominance of the Western-type cagA gene in a Venezuelan admixed population. This is the first report showing oipA status of H. pylori strains in Venezuela. Further studies with a larger number of samples and including other pathologies are necessary to continue evaluating the role of the H. pylori virulence factors in the prevalence of gastric diseases in our country.

  1. Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro.

    PubMed

    Whitmore, Laura C; Weems, Megan N; Allen, Lee-Ann H

    2017-03-01

    Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62L(dim), CD16(bright), CD11b(bright), CD66b(bright), CD63(bright) surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil-H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease.

  2. Helicobacter pylori and gastric cancer in the Middle East: A new enigma?

    PubMed Central

    Hussein, Nawfal R

    2010-01-01

    The Middle East is the home of ethnic groups from three main backgrounds: Semitic (Arabs and Jews), Indo-European (Persians and Kurdish) and Turkic (Turkish and Turkmens). Its geographic location, which has been under continuous influences from Asia, Europe and Africa, has made it an ideal site for epidemiological studies on Helicobacter pylori (H. pylori) infection and genotyping. The gastric cancer rate differs in this region from very high in Iran (26.1/105) to low in Israel (12.5/105) and very low in Egypt (3.4/105). Epidemiological studies showed that the prevalence of H. pylori is almost similar in those countries with a high level of infection in childhood. Importantly, the frequency of vacA s1 and m1 regions and cagA+ genotypes were higher in non Semitic populations who inhabit the North than Semitic populations, the inhabitants of Southern parts of the Middle East. H. pylori infection prevalence, distribution pattern of virulence factors, diet and smoking could not have explained the difference in cancer rate. This reflects the multifactorial aetiology of gastric cancer and suggests that H. pylori infection does not always directly correlate with the risk for gastrointestinal disease, such as gastric cancer. Further detailed investigations and international comparative studies of each risk factor need to be performed to investigate whether this represents a true enigma. PMID:20614477

  3. Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro

    PubMed Central

    Whitmore, Laura C.; Weems, Megan N.

    2017-01-01

    Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62Ldim, CD16bright, CD11bbright, CD66bbright, CD63bright surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil–H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease. PMID:28148734

  4. Stool Test: H. Pylori Antigen

    MedlinePlus

    ... Your 1- to 2-Year-Old Stool Test: H. Pylori Antigen KidsHealth > For Parents > Stool Test: H. Pylori Antigen A A A What's in this article? ... en español Muestra de materia fecal: antígeno de H. pylori What It Is Helicobacter pylori ( H. pylori ) bacteria ...

  5. Differences in interleukin 8 expression in Helicobacter pylori-infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic.

    PubMed

    Nagashima, Hiroyuki; Iwatani, Shun; Cruz, Modesto; Jiménez Abreu, José A; Tronilo, Lourdes; Rodríguez, Eduardo; Disla, Mildre; Terao, Hideo; Uchida, Tomohisa; Mahachai, Varocha; Vilaichone, Ratha-Korn; Tshering, Lotay; Mitsui, Takahiro; Shiota, Seiji; Graham, David Y; Yamaoka, Yoshio

    2015-01-01

    The outcomes of Helicobacter pylori infection vary geographically. H pylori strains, disease presentation, and environments differ markedly in Bhutan and Dominican Republic. The aims were to compare the strains, histology, and expression of interleukin (IL) 8 and IL-10 from gastric mucosa from the 2 countries. H pylori status was assessed by the combination of rapid urease test, culture, and histology. Histology was evaluated using the updated Sydney System, and cytokines in gastric biopsies were measured using real-time polymerase chain reaction (PCR). There were 138 subjects from Bhutan and 155 from Dominican Republic. The prevalence of H pylori infection was 65% and 59%, respectively. The genotype of cagA was predominantly East Asian type in Bhutan versus Western type in Dominican Republic. Gastritis severity was significantly higher in H pylori-infected subjects from Bhutan than those from Dominican Republic. IL-8 expression by H pylori infection was 5.5-fold increased in Bhutan versus 3-fold in Dominican Republic (P < .001); IL-10 expression was similar. IL-8 expression levels among H pylori-infected cases tended to be positively correlated with polymorphonuclear leucocyte and monocyte infiltration scores in both countries. IL-8 expression among those with grade 2 and 3 polymorphonuclear leucocyte and monocyte infiltration was significantly higher in Bhutan than in Dominican Republic. The difference in IL-8 expression in the 2 countries is reflected in the different disease pattern between them. Whether the dominant factor is differences in H pylori virulence, in host-H pylori-environmental interactions, genetic factors or all remains unclear. However, severity of inflammation appears to be a critical factor in disease pathogenesis. We compared IL-8 messenger RNA levels between the high gastric cancer risk country, Bhutan (mainly East Asian-type H pylori), and the lower gastric cancer risk country, Dominican Republic (mainly Western-type H pylori).

  6. Microbiota studies in the bile duct strongly suggest a role for Helicobacter pylori in extrahepatic cholangiocarcinoma.

    PubMed

    Avilés-Jiménez, F; Guitron, A; Segura-López, F; Méndez-Tenorio, A; Iwai, S; Hernández-Guerrero, A; Torres, J

    2016-02-01

    Biliary tract cancer or extrahepatic cholangiocarcinoma (ECCA) represents the sixth commonest cause of cancer in the gastrointestinal tract in western countries. We aimed to characterize the microbiota and its predicted associated functions in the biliary tract of ECCA and benign biliary pathology (BBP). Samples were taken from 100 patients with ECCA and 100 patients with BBP by endoscopic cholangio-pancreatography for DNA extraction. Ten patients with ECCA and ten with BBP were selected for microbiota studies using the V4-16S rRNA gene and sequenced in Illumina platform. Microbiota analyses included sample-to-sample distance metrics, ordination/clustering and prediction of functions. Presence of Nesterenkonia sp. and Helicobacter pylori cagA and vacA genes were tested in the 100 ECCA and 100 BBP samples. Phylum Proteobacteria dominated all samples (60.4% average). Ordination multicomponent analyses showed significant microbiota separation between ECCA and BBP (p 0.010). Analyses of 4002 operational taxonomic units with presence variation in at least one category probed a separation of ECCA from BBP. Among these, Nesterenkonia decreased, whereas Methylophilaceae, Fusobacterium, Prevotella, Actinomyces, Novosphingobium and H. pylori increased in ECCA. Predicted associated functions showed increased abundance of H. pylori virulence genes in ECCA. cagA and vacA genes were confirmed by PCR in ECCA and BBP samples. This is the first microbiota report in ECCA and BBP to show significant changes in microbial composition. Bacterial species unusual for human flora were found: Methylophilaceae and Nesterenkonia are reported in hypersaline soils, and Mesorhizobium is a nitrogen-fixing bacterium. Enrichment of virulence genes confirms previous studies suggesting that H. pylori might be associated with ECCA.

  7. Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

    PubMed Central

    Kamangar, F; Qiao, Y-L; Blaser, M J; Sun, X-D; Katki, H; Fan, J-H; Perez-Perez, G I; Abnet, C C; Zhao, P; Mark, S D; Taylor, P R; Dawsey, S M

    2006-01-01

    In a cohort of 29 584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case–cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26–2.14, and 1.60; 1.15–2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88–1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies. PMID:17179990

  8. Partial characterization of a cell proliferation-inhibiting protein produced by Helicobacter pylori.

    PubMed Central

    Knipp, U; Birkholz, S; Kaup, W; Opferkuch, W

    1996-01-01

    Despite the induction of an immunological reaction, Helicobacter pylori-associated gastritis is a chronic disease, suggesting that this microbe can evade the host immune defense. Previous studies by our group showed that H. pylori suppresses the in vitro proliferative response of human mononuclear cells to mitogens and antigens. Here we demonstrate that the antiproliferative activity of H. pylori also affects the proliferation of various mammalian cell lines (U937, Jurkat, AGS, Kato-3, HEP-2, and P388D1). This effect is detectable in the first 16 h of incubation and maximal between 24 and 48 h. In addition, the presence of H. pylori significantly diminished the protein synthesis of cells in the first 6 h of incubation, comparable to the results with cycloheximide and diphtheria toxin. The urease enzyme, the cagA gene product, and the vacuolizing cytotoxin of H. pylori were excluded as causative agents of the antiproliferative effect by using isogenic knockout mutant strains. The inhibitory effect was not due to a lytic activity of this bacterium. The results reported here indicate that the responsible factor is a protein with an apparent native molecular mass of 100 +/- 10 kDa. Our work implicates the presence of a protein factor in H. pylori (termed PIP [for proliferation-inhibiting protein]) with antiproliferative activity for mammalian cells, including immunocompetent and epithelial cells. Thus, it is reasonable to presume that this property may contribute to the pathogenesis of H. pylori-induced diseases. It may be involved on the one hand in immune response evasion and on the other hand in the suppression of epithelial repair mechanisms. PMID:8751889

  9. An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

    PubMed Central

    Chung, Woo Chul; Joo, Kyu Re; Kim, Min Ji; Youn, Gun Jung; Kim, Yaeni; Lee, Joune Seup; Lee, Hyewon; Jung, Ji Han; Lee, Yun Kyung

    2013-01-01

    Background/Aims This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. Methods We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. Results The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). Conclusions Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype. PMID:24312710

  10. Efficacy of the antimicrobial peptide TP4 against Helicobacter pylori infection: in vitro membrane perturbation via micellization and in vivo suppression of host immune responses in a mouse model

    PubMed Central

    Narayana, Jayaram Lakshmaiah; Huang, Han-Ning; Wu, Chang-Jer; Chen, Jyh-Yih

    2015-01-01

    Helicobacter pylori infection is marked by a strong association with various gastric diseases, including gastritis, ulcers, and gastric cancer. Antibiotic treatment regimens have low success rates due to the rapid occurrence of resistant H. pylori strains, necessitating the development of novel anti-H. pylori strategies. Here, we investigated the therapeutic potential of a novel peptide, Tilapia Piscidin 4 (TP4), against multidrug resistant gastric pathogen H. pylori, based on its in vitro and in vivo efficacy. TP4 inhibited the growth of both antibiotic-sensitive and -resistant H. pylori (CagA+, VacA+) via membrane micelle formation, which led to membrane depolarization and extravasation of cellular constituents. During colonization of gastric tissue, H. pylori infection maintains high T regulatorysubsets and a low Th17/Treg ratio, and results in expression of both pro- and anti-inflammatory cytokines. Treatment with TP4 suppressed Treg subset populations and pro- and anti-inflammatory cytokines. TP4 restored the Th17/Treg balance, which resulted in early clearance of H. pylori density and recovery of gastric morphology. Toxicity studies demonstrated that TP4 treatment has no adverse effects in mice or rabbits. The results of this study indicate that TP4 may be an effective and safe monotherapeutic agent for the treatment of multidrug resistant H. pylori infections. PMID:26002554

  11. Characterization of the low-pH responses of Helicobacter pylori using genomic DNA arrays.

    PubMed

    Allan, E; Clayton, C L; McLaren, A; Wallace, D M; Wren, B W

    2001-08-01

    Helicobacter pylori is unique among bacterial pathogens in its ability to persist in the acidic environment of the human stomach. To identify H. pylori genes responsive to low pH, the authors assembled a high-density array of PCR-amplified random genomic DNA. Hybridization of radiolabelled cDNA probes, prepared using total RNA from bacteria exposed to buffer at either pH 4.0 or pH 7.0, allowed both qualitative and quantitative information on differential gene expression to be obtained. A previously described low-pH-induced gene, cagA, was identified together with several novel genes that may have relevance to the survival and persistence of H. pylori in the gastric environment. These include genes encoding enzymes involved in LPS and phospholipid synthesis and secF, encoding a component of the protein export machinery. A hypothetical protein unique to H. pylori (HP0681) was also found to be acid induced. Genes down-regulated at pH 4.0 include those encoding a sugar nucleotide biosynthesis protein, a flagellar protein and an outer-membrane protein. Differential gene expression was confirmed by total RNA slot-blot hybridization.

  12. Coiled Coil Rich Proteins (Ccrp) Influence Molecular Pathogenicity of Helicobacter pylori

    PubMed Central

    Schätzle, Sarah; Specht, Mara; Waidner, Barbara

    2015-01-01

    Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak “scattering/hummingbird” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen. PMID:25822999

  13. Down-regulated Th17 Responses Are Associated with Reduced Gastritis in Helicobacter pylori-infected Children

    PubMed Central

    Bimczok, Diane; Shaffer, Carrie L.; Cover, Timothy L.; Venegas, Alejandro; Salazar, Maria G.; Smythies, Lesley E.; Harris, Paul R.; Smith, Phillip D.

    2013-01-01

    Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated Th17 responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of IL-17-specific mRNA and protein compared to infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10+ cells and increased levels of both IL-10 and Foxp3 mRNA compared to that of infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to down-regulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T cell activity in the children. PMID:23299619

  14. Control of gene expression in Helicobacter pylori using the Tet repressor

    PubMed Central

    McClain, Mark S.; Duncan, Stacy S.; Gaddy, Jennifer A.; Cover, Timothy L.

    2013-01-01

    The lack of a versatile system to control gene expression in Helicobacter pylori has hampered efforts to study H. pylori physiology and pathogenesis. To overcome these limitations, we evaluated the utility of an inducible system based on the well-characterized Tet repressor (TetR) and Tet operator (tetO). As validation of this system, we introduced three copies of tetO into the promoter region upstream of the cagUT operon (encoding two virulence factors required for function of the H. pylori Cag type IV secretion system) and expressed tetR by introducing a codon-optimized gene into the chromosomal ureA locus. Introduction of the tetO copies upstream of cagUT did not disrupt promoter activity, as determined by immunoblotting for CagT. The subsequent introduction of tetR, however, did repress CagT synthesis. Production of CagT was restored when strains were cultured in the presence of the inducer, anhydrotetracycline. To demonstrate one potential application of this new tool, we analyzed the function of the Cag type IV secretion system. When the modified H. pylori strains were co-cultured with AGS cells, activity of the Cag type IV secretion system was dependent on the presence of anhydrotetracycline as evidenced by inducer-dependent induction of IL-8 secretion, CagA translocation, and appearance of type IV secretion system pili at the bacteria-host interface. These studies demonstrate the effectiveness of the tetR-tetO system to control gene expression in H. pylori and provide an improved system for studying H. pylori physiology and pathogenesis. PMID:24113399

  15. homB status of Helicobacter pylori as a novel marker to distinguish gastric cancer from duodenal ulcer.

    PubMed

    Jung, Sung Woo; Sugimoto, Mitsushige; Graham, David Y; Yamaoka, Yoshio

    2009-10-01

    The hom family of Helicobacter pylori outer-membrane proteins, especially the homB gene, has been suggested as a novel virulence factor; however, the clinical association and function of this gene are still unclear. We evaluated the presence of the homA, homB, and cagA genes in 286 strains isolated from patients in the U.S. and Colombian populations (126 with gastritis, 96 with duodenal ulcer, and 64 with gastric cancer) by PCR. The results were compared with the clinical presentation and gastric injury. The prevalence of the homB gene was significantly higher in strains isolated from gastric-cancer patients (71.9%) than in those from duodenal ulcer patients (52.1%) (P = 0.012). In a multivariate analysis, the presence of the cagA gene significantly increased the risk for developing gastric cancer and duodenal ulcer, with the presence of the homB gene acting as a factor that could distinguish gastric cancer from duodenal ulcer (adjusted odds ratio, 3.033; 95% confidence interval, approximately 1.37 to approximately 6.73). cagA status was correlated with homB status (r = 0.323; P < 0.01). A histological analysis showed that cagA status was associated with inflammation and atrophy both in the antrum and in the corpus, while homB status was associated with inflammation and atrophy in the corpus. homB gene status might be susceptible to gastric-cancer development such that the homB gene is used as a factor for discriminating the risk of gastric cancer from that of duodenal ulcer.

  16. MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

    PubMed Central

    Lindén, Sara K.; Sheng, Yong H.; Every, Alison L.; Miles, Kim M.; Skoog, Emma C.; Florin, Timothy H. J.; Sutton, Philip; McGuckin, Michael A.

    2009-01-01

    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. PMID:19816567

  17. Analysis of Genomic Diversity among Helicobacter pylori Strains Isolated from Iranian Children by Pulsed Field Gel Electrophoresis

    PubMed Central

    Falsafi, Tahereh; Sotoudeh, Nazli; Feizabadi, Mohammad-Mehdi; Mahjoub, Fatemeh

    2014-01-01

    Objective: Presence of genomic diversity among Helicobacter pylori (H. pylori) strains have been suggested by numerous investigators. Little is known about diversity of H. pylori strains isolated from Iranian children and their association with virulence of the strains. Our purpose was to assess the degree of genomic diversity among H. pylori strains isolated from Iranian-children, on the basis of vacA genotype, cagA status of the strains, sex, age as well as the pathological status of the patients. Methods: Genomic DNA from 44 unrelated H. pylori strains isolated during 1997–2009, was examined by pulse-field gel electrophoresis (PFGE). Pathological status of the patients was performed according to the modified Sydney-system and genotype/status of vacA/cagA genes was determined by PCR. PFGE was performed using XbaI restriction-endonuclease and the field inversion-gel electrophoresis system. Findings: No significant relationship was observed between the patterns of PFGE and the cagA/vacA status/genotype. Also no relationship was observed between age, sex, and pathological status of the children and the PFGE patterns of their isolates. Similar conclusion was obtained by Total Lab software. However, more relationship was observed between the strains isolated in the close period (1997–2009, 2001–2003, 2005–2007, and 2007–2009) and more difference was observed among those obtained in the distant periods (1997 and 2009). Conclusion: H. pylori strains isolated from children in Iran are extremely diverse and this diversity is not related to their virulence characteristics. Occurrence of this extreme diversity may be related to adaptation of H. pylori strains to variable living conditions during transmission between various host individuals. PMID:26019775

  18. A study of Helicobacter pylori outer-membrane proteins (hom) A and B in Iraq and Turkey.

    PubMed

    Hussein, Nawfal R

    2011-08-01

    Helicobacter pylori outer-membrane proteins (hom), especially the homB gene, have been suggested as a novel virulence factor. However, no study has been conducted in Middle Eastern countries regarding the association between these genes and clinical outcome. Gastric biopsies were obtained from 70 and 64 unselected H. pylori+ patients from Iraq and Turkey, respectively. PCR was performed to study the presence of the homA, homB, and cagA. No association was found between homA or homB and clinical outcomes. When Iraqi and Turkish strains were combined as Middle Eastern samples, cagA positivity was significantly higher in patients with peptic ulcer disease (PUD) than those with non-peptic ulcer disease (NPUD) (p=0.003, OR=3.6, CI=1.5-8.8). Two Iraqi strains showed intermediate, non-homA non-homB, length PCR products. The function of such gene is yet to be determined. In conclusion, hom genes might not be a good indicator for disease prediction in the Middle East. More studies are needed to confirm these results and determine the function of intermediate length hom.

  19. Tests for H. pylori

    MedlinePlus

    ... special substance that has urea. Urea is a waste product the body produces as it breaks down protein. The urea used in the test has been made harmlessly radioactive. If H. pylori are present, the bacteria convert ...

  20. Molecular Epidemiology of Helicobacter pylori Infection in Nepal: Specific Ancestor Root

    PubMed Central

    Miftahussurur, Muhammad; Sharma, Rabi Prakash; Shrestha, Pradeep Krishna; Suzuki, Rumiko; Uchida, Tomohisa; Yamaoka, Yoshio

    2015-01-01

    Prevalence of Helicobacter pylori infection in Nepal, a low-risk country for gastric cancer, is debatable. To our knowledge, no studies have examined H. pylori virulence factors in Nepal. We determined the prevalence of H. pylori infection by using three different tests, and the genotypes of virulence factors were determined by PCR followed by sequencing. Multilocus sequence typing was used to analyze the population structure of the Nepalese strains. The prevalence of H. pylori infection in dyspeptic patients was 38.4% (56/146), and was significantly related with source of drinking water. In total, 51 strains were isolated and all were cagA-positive. Western-type-cagA (94.1%), cagA pre-EPIYA type with no deletion (92.2%), vacA s1a (74.5%), and m1c (54.9%) were the predominant genotypes. Antral mucosal atrophy levels were significantly higher in patients infected with vacA s1 than in those infected with s2 genotypes (P = 0.03). Several Nepalese strains were H. pylori recombinants with genetic features of South Asian and East Asian genotypes. These included all East-Asian-type-cagA strains, with significantly lesser activity and inflammation in the corpus than the strains of the specific South Asian genotype (P = 0.03 and P = 0.005, respectively). Although the population structure confirmed that most Nepalese strains belonged to the hpAsia2 population, some strains shared hpEurope- and Nepalese-specific components. Nepalese patients infected with strains belonging to hpEurope showed higher inflammation in the antrum than strains from the Nepalese specific population (P = 0.05). These results support that ancestor roots of Kathmandu`s people not only connected with India alone. PMID:26226153

  1. Influence of Helicobacter pylori infection on levels of ghrelin and obestatin in human semen.

    PubMed

    Moretti, Elena; Collodel, Giulia; Campagna, Maria Stella; Franci, Maria Beatrice; Iacoponi, Francesca; Mazzi, Lucia; Figura, Natale

    2012-01-01

    Helicobacter pylori (HP) infection might have negative effects on the semen parameters of infertile men. We explored the possibility that this infection can influence systemic and seminal levels of ghrelin and obestatin, hormones mainly produced by the stomach. Ghrelin and obestatin exert many activities, including the regulation of reproductive biology, and are present in many organs and fluids, including human semen. In 78 men, we determined HP infection and cytotoxin-associated gene A protein (CagA) status by enzyme-linked immunosorbent assay and Western blotting, semen quality following World Health Organization guidelines, and ghrelin and obestatin levels in the blood stream (47 subjects) and semen by radioimmunoassay. Twenty-seven men (34.6%) were infected (HP+) and 11 out of 27 infected men (40.7%) were seropositive for CagA (CagA+). Sperm motility was significantly reduced in HP+/CagA+ men compared with HP+/CagA- men (P < .01). Ghrelin semen levels were decreased in HP+ men compared with uninfected individuals (P < .05), whereas they were increased in HP+/CagA+ men compared with HP+/CagA- subjects (P < .01). Ghrelin semen concentrations in HP+/CagA- men were lower than those measured in uninfected subjects (P < .001). Semen obestatin concentration was increased, in a nonsignificant manner, in HP+/CagA+ men. The obestatin levels were approximately 4 times higher than those of ghrelin in semen and approximately half the levels of ghrelin in serum specimens of all the analyzed groups. No significant differences were found in systemic levels of ghrelin and obestatin in HP+ to uninfected individuals. HP infection may influence the ghrelin seminal concentrations, probably as a response to a negative effect of infection on the semen quality.

  2. Impact of cagPAI and T4SS on the Inflammatory Response of Human Neutrophils to Helicobacter pylori Infection

    PubMed Central

    Sánchez-Zauco, Norma Angélica; Torres, Javier; Pérez-Figueroa, Gloria Erandi; Álvarez-Arellano, Lourdes; Camorlinga-Ponce, Margarita; Gómez, Alejandro; Giono-Cerezo, Silvia; Maldonado-Bernal, Carmen

    2013-01-01

    Helicobacter pylori contains a pathogenicity island, cagPAI, with genes homologous to components of the type IV secretion system (T4SS) of Agrobacterium tumefaciens. The T4SS components assemble a structure that transfers CagA protein and peptidoglycan into host epithelial cells, causing the increased release of interleukin 8 (IL8) from the cells. The Toll-like receptors on neutrophils recognize H. pylori, initiating signaling pathways that enhance the activation of NF-κB. However, the roles of cagPAI and T4SS in the inflammatory response of neutrophils are unknown. We evaluated the participation of cagPAI and T4SS in the response of human neutrophils to H. pylori infection. Neutrophils were isolated from the blood of healthy donors and infected with H. pylori cagPAI+, cagPAI–, and cagPAI mutant strains virB4– and virD4–. Whereas cagPAI+ strain 26695 induced the greatest IL8 production, a proinflammatory response, cagPAI– strain 8822 induced the greatest IL10 production, an anti-inflammatory response. In contrast, the virB4– and virD4– mutant strains produced significantly more of the two proinflammatory cytokines IL1β and tumor necrosis factor αthan the cagPAI+ strain 26695. We observed that H. pylori downregulated the expression of TLRs 2 and 5 but upregulated TLR9 expression in a cagPAI and T4SS-independent manner. These results show for the first time that the response of human neutrophils to H. pylori may vary from a pro-inflammatory to an anti-inflammatory response, depending on cagPAI and the integrity of T4SS. PMID:23755130

  3. Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system.

    PubMed

    Backert, Steffen; Tegtmeyer, Nicole; Fischer, Wolfgang

    2015-01-01

    Many Gram-negative pathogens harbor type IV secretion systems (T4SS) that translocate bacterial virulence factors into host cells to hijack cellular processes. The pathology of the gastric pathogen Helicobacter pylori strongly depends on a T4SS encoded by the cag pathogenicity island. This T4SS forms a needle-like pilus, and its assembly is accomplished by multiple protein-protein interactions and various pilus-associated factors that bind to integrins followed by delivery of the CagA oncoprotein into gastric epithelial cells. Recent studies revealed the crystal structures of six T4SS proteins and pilus formation is modulated by iron and zinc availability. All these T4SS interactions are crucial for deregulating host signaling events and disease progression. New developments in T4SS functions and their importance for pathogenesis are discussed.

  4. MicroRNA-320a and microRNA-4496 attenuate Helicobacter pylori cytotoxin-associated gene A (CagA)-induced cancer-initiating potential and chemoresistance by targeting β-catenin and ATP-binding cassette, subfamily G, member 2.

    PubMed

    Kang, Dong Woo; Yang, Eun Sun; Noh, Yu Na; Hwang, Won Chan; Jo, Se-Young; Suh, Young-Ah; Park, Won Sang; Choi, Kang-Yell; Min, Do Sik

    2017-04-01

    Infection with Helicobacter pylori is closely linked to an increased risk of gastric cancer. Although cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is known to be a causal factor for gastric carcinogenesis, the molecular link between CagA and gastric cancer-initiating cell (CIC)-like properties remains elusive. Here, we demonstrate that CagA is required for increased expression of β-catenin and its target CIC markers via downregulation of microRNA (miR)-320a and miR-4496. CagA promoted gastric CIC properties and was responsible for chemoresistance. miR-320a and miR-4496 attenuated the in vitro self-renewal and tumour-initiating capacity of CagA-expressing CICs by targeting β-catenin. Moreover, miR-320a and miR-4496 decreased CagA-induced chemoresistance by targeting ATP-binding cassette, subfamily G, member 2 (ABCG2) at the transcriptional and post-transcriptional levels, respectively. Combination therapy with 5-fluorouracil and miR-320a/miR-4496 suppressed gastric tumourigenesis and metastatic potential in an orthotopic mouse model, probably via suppression of CagA-induced CIC properties and chemoresistance. Our results provide novel evidence that CIC properties, chemoresistance and tumourigenesis associated with H. pylori are linked to CagA-induced upregulation of β-catenin and ABCG2. These data provide novel insights into the molecular mechanisms of CagA-induced carcinogenisis and the therapeutic potential of of miR-320a and miR-4496. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. Helicobacter pylori eradication therapy.

    PubMed

    Suzuki, Hidekazu; Nishizawa, Toshihiro; Hibi, Toshifumi

    2010-04-01

    Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.

  6. Fallacy of the Unique Genome: Sequence Diversity within Single Helicobacter pylori Strains

    PubMed Central

    Hansen, Lori M.; Bernick, David L.; Abedrabbo, Samar; Underwood, Jason G.; Kong, Nguyet; Huang, Bihua C.; Weis, Allison M.; Pourmand, Nader

    2017-01-01

    ABSTRACT Many bacterial genomes are highly variable but nonetheless are typically published as a single assembled genome. Experiments tracking bacterial genome evolution have not looked at the variation present at a given point in time. Here, we analyzed the mouse-passaged Helicobacter pylori strain SS1 and its parent PMSS1 to assess intra- and intergenomic variability. Using high sequence coverage depth and experimental validation, we detected extensive genome plasticity within these H. pylori isolates, including movement of the transposable element IS607, large and small inversions, multiple single nucleotide polymorphisms, and variation in cagA copy number. The cagA gene was found as 1 to 4 tandem copies located off the cag island in both SS1 and PMSS1; this copy number variation correlated with protein expression. To gain insight into the changes that occurred during mouse adaptation, we also compared SS1 and PMSS1 and observed 46 differences that were distinct from the within-genome variation. The most substantial was an insertion in cagY, which encodes a protein required for a type IV secretion system function. We detected modifications in genes coding for two proteins known to affect mouse colonization, the HpaA neuraminyllactose-binding protein and the FutB α-1,3 lipopolysaccharide (LPS) fucosyltransferase, as well as genes predicted to modulate diverse properties. In sum, our work suggests that data from consensus genome assemblies from single colonies may be misleading by failing to represent the variability present. Furthermore, we show that high-depth genomic sequencing data of a population can be analyzed to gain insight into the normal variation within bacterial strains. PMID:28223462

  7. Bacteriology of Helicobacter pylori.

    PubMed

    Owen, R J

    1995-09-01

    The discovery and first isolation of H. pylori in pure culture from gastric biopsies in 1982 provided the basis for a completely new area of microbiology. Since then, H. pylori has been an intensively pursued topic world-wide, and extensive data have been acquired on all aspects of its basic microbiology, both at the conventional phenotypic level and at the molecular level. H. pylori is a remarkable microorganism because of its ability to readily colonize a major proportion of human population worldwide and to persist successfully for long periods (probably decades) in a hostile environment. At the same time it interacts with the host immune system in such a way as to permit long-term survival. Blaser (1993) proposed a model in which both host and parasite adapt to down regulate inflammatory phenomena to promote survival. Urease production by H. pylori (an important factor in that process) is one of its most distinct features with a key role in its success as an infective agent. Another less obvious yet highly significant feature of H. pylori is the ability to achieve a high degree of interstrain diversity in genomic DNA nucleotide sequences, while maintaining overall genetic homology and phenotypic homogeneity amongst strains. The selective advantage this diversity provides the bacterium is not understood. A key objective of future microbiological studies should be to understand the population genetic structure of H. pylori. Most species of bacteria are clonal in natural population structure, yet all genomic data suggest the contrary is true for H. pylori. Furthermore, it is not clear if all strains of H. pylori are equally pathogenic, and that some subsets may possess additional pathogenicity factors that are responsible for the development of different disease pathologies. A phylogenetic framework of the genetic relationships of the clones within H. pylori would enable an examination of the total genetic diversity, with respect to ethnic or geographical

  8. High resolution electron microscopy of the Helicobacter pylori Cag type IV secretion system pili produced in varying conditions of iron availability.

    PubMed

    Haley, Kathryn Patricia; Blanz, Eric Joshua; Gaddy, Jennifer Angeline

    2014-11-21

    Helicobacter pylori is a helical-shaped, gram negative bacterium that colonizes the human gastric niche of half of the human population. H. pylori is the primary cause of gastric cancer, the second leading cause of cancer-related deaths worldwide. One virulence factor that has been associated with increased risk of gastric disease is the Cag-pathogenicity island, a 40-kb region within the chromosome of H. pylori that encodes a type IV secretion system and the cognate effector molecule, CagA. The Cag-T4SS is responsible for translocating CagA and peptidoglycan into host epithelial cells. The activity of the Cag-T4SS results in numerous changes in host cell biology including upregulation of cytokine expression, activation of proinflammatory pathways, cytoskeletal remodeling, and induction of oncogenic cell-signaling networks. The Cag-T4SS is a macromolecular machine comprised of sub-assembly components spanning the inner and outer membrane and extending outward from the cell into the extracellular space. The extracellular portion of the Cag-T4SS is referred to as the "pilus". Numerous studies have demonstrated that the Cag-T4SS pili are formed at the host-pathogen interface(. However, the environmental features that regulate the biogenesis of this important organelle remain largely obscure. Recently, we reported that conditions of low iron availability increased the Cag-T4SS activity and pilus biogenesis. Here we present an optimized protocol to grow H. pylori in varying conditions of iron availability prior to co-culture with human gastric epithelial cells. Further, we present the comprehensive protocol for visualization of the hyper-piliated phenotype exhibited in iron restricted conditions by high resolution scanning electron microscopy analyses.

  9. Helicobacter pylori Infection in Pediatrics.

    PubMed

    Roma, Eleftheria; Miele, Erasmo

    2015-09-01

    This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.

  10. Vacuolating Cytotoxin Genotypes Are Strong Markers of Gastric Cancer and Duodenal Ulcer-Associated Helicobacter pylori Strains: a Matched Case-Control Study

    PubMed Central

    Hussein, Nawfal R.; Miendje Deyi, Véronique Y.; Burette, Alain; Atherton, John C.

    2014-01-01

    The Helicobacter pylori virulence gene, cagA, and active forms of the vacuolating cytotoxin gene, vacA, are major determinants of pathogenesis. However, previous studies linking these factors to disease risk have often included patients using aspirin/nonsteroidal anti-inflammatory agents (NSAIDs) or acid-suppressing drugs, both of which may confound results. Also, particularly for gastric cancer (GC), controls have often been of quite different ages. Here, we performed a careful study in a “clean” Belgian population with gastric cancer cases age and sex matched to 4 controls and with a parallel duodenal ulcer (DU) group. As in other populations, there was a close association between the presence of cagA and the vacA s1 genotype. For GC, associations were found for vacA s1-positive (P = 0.01, odds ratio [OR], 9.37; 95% confidence interval [CI], 1.16 to 201.89), i1-positive (P = 0.003; OR, 12.08; 95% CI, 1.50 to 259.64), and cagA-positive status (P < 0.05; OR, infinity; 95% CI, 0.76 to infinity). For DU, associations were found with vacA s1 (P = 0.002; OR, 6.04; 95% CI, 1.52 to 27.87) and i1 (P = 0.004; OR, 4.35; 95% CI, 1.36 to 14.78) status but not with cagA status. Neither condition showed independent associations with the vacA m1 allele or with more biologically active forms of cagA with longer 3′ variable regions. In this Belgian population, the best markers of gastric cancer- and duodenal ulcer-associated strains are the vacA s1 and i1 genotypes. This fits with experimental data showing that the s and i regions are the key determinants of vacuolating cytotoxin activity. PMID:24920772

  11. Genetic characterisation of Helicobacter pylori isolates from an Argentinean adult population based on cag pathogenicity island right-end motifs, lspA-glmM polymorphism and iceA and vacA genotypes.

    PubMed

    Leanza, A G; Matteo, M J; Crespo, O; Antelo, P; Olmos, J; Catalano, M

    2004-09-01

    Isolates of Helicobacter pylori from 88 patients were characterised by cagA status, cagA pathogenicity island (PAI) right-end motifs, iceA, vacA and lspA-glmM genotypes, primarily by PCR-based analysis, to investigate whether Argentinean isolates differed from those recovered in southern Europe or other Latin American countries. PCR-based analysis of vacA alleles was confirmed by reverse hybridisation in 56 cases, while sequence analysis was performed either when iceA and vacA genotypes could not be determined by PCR, or to investigate PCR and reverse hybridisation vacA genotyping discordance. Typing by lspA-glmM restriction fragment length polymorphism was performed with HhaI and AluI. The pattern of cag PAI right-end motifs and the prevalence of type Ia were similar to those in isolates from southern European countries, with cagA(+)/iceA1/vacA-s1 m1 being the commonest genotype. Reverse hybridisation identified a vacA-s1a/s1b recombinant allele, confirmed by sequencing analysis. Analysis of lspA-glmM genotypes identified at least 73 unrelated strains. Few mixed infections were identified, but in one case, isolates from a single biopsy exhibiting two vacA alleles were shown by lspA-glmM fingerprints to be two unrelated strains. No associated effect on ulcer disease risk was demonstrated by analysis of cagA, vacA and iceA status. Overall, the isolates of H. pylori from Argentina were similar to isolates from southern Europe or Latin American countries, and infections were associated mainly with single H. pylori strains.

  12. Halitosis and helicobacter pylori infection

    PubMed Central

    Dou, Wenhuan; Li, Juan; Xu, Liming; Zhu, Jianhong; Hu, Kewei; Sui, Zhenyu; Wang, Jianzong; Xu, Lingling; Wang, Shaofeng; Yin, Guojian

    2016-01-01

    Abstract Background: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to define the correlation between H pylori infection and halitosis. Objectives: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication therapy will help relieve halitosis. Methods: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Screening of titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done using Review Manager 5.2 software. Results: A total of 115 articles were identified, 21 of which met the inclusion criteria and presented data that could be used in the analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis-negative patients was 4.03 (95% CI: 1.41–11.50; P = 0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative patients was 2.85 (95% CI: 1.40–5.83; P = 0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected halitosis-positive patients was 0.17 (95% CI: 0.08–0.39; P <0.0001), compared with those patients without successful H pylori eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45–15.80; P = 0.01), compared with after successful H

  13. [Helicobacter pylori and Arteriosclerosis].

    PubMed

    Matsui, Teruaki

    2011-03-01

    Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B₁₂ (VB₁₂) and folic acid. However, deficiency of VB₁₂ and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB₁₂ and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB₁₂ and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB₁₂ and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their

  14. Free recombination within Helicobacter pylori

    PubMed Central

    Suerbaum, Sebastian; Smith, John Maynard; Bapumia, Khairun; Morelli, Giovanna; Smith, Noel H.; Kunstmann, Erdmute; Dyrek, Isabelle; Achtman, Mark

    1998-01-01

    Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent that different loci and polymorphisms within each locus are all at linkage equilibrium. These results indicate that H. pylori is panmictic. Comparisons with sequences from Escherichia coli, Neisseria meningitidis, and Drosophila melanogaster showed that recombination in H. pylori was much more frequent than in other species. In contrast, when multiple family members infected with H. pylori were investigated, some strains were indistinguishable at all three loci. Thus, H. pylori is clonal over short time periods after natural transmission. PMID:9770535

  15. The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence

    PubMed Central

    Haley, Kathryn P.; Delgado, Alberto G.; Piazuelo, M. Blanca; Mortensen, Brittany L.; Correa, Pelayo; Damo, Steven M.; Chazin, Walter J.; Skaar, Eric P.

    2015-01-01

    During infectious processes, antimicrobial proteins are produced by both epithelial cells and innate immune cells. Some of these antimicrobial molecules function by targeting transition metals and sequestering these metals in a process referred to as “nutritional immunity.” This chelation strategy ultimately starves invading pathogens, limiting their growth within the vertebrate host. Recent evidence suggests that these metal-binding antimicrobial molecules have the capacity to affect bacterial virulence, including toxin secretion systems. Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, or calgranulin A/B) binds zinc and represses the elaboration of the H. pylori cag type IV secretion system (T4SS). However, there are several other S100 proteins that are produced in response to infection. We hypothesized that the zinc-binding protein S100A12 (calgranulin C) is induced in response to H. pylori infection and also plays a role in controlling H. pylori growth and virulence. To test this, we analyzed gastric biopsy specimens from H. pylori-positive and -negative patients for S100A12 expression. These assays showed that S100A12 is induced in response to H. pylori infection and inhibits bacterial growth and viability in vitro by binding nutrient zinc. Furthermore, the data establish that the zinc-binding activity of the S100A12 protein represses the activity of the cag T4SS, as evidenced by the gastric cell “hummingbird” phenotype, interleukin 8 (IL-8) secretion, and CagA translocation assays. In addition, high-resolution field emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that S100A12 represses biogenesis of the cag T4SS. Together with our previous work, these data reveal that multiple S100 proteins can repress the elaboration of an oncogenic bacterial surface organelle. PMID:25964473

  16. Detailed analysis of Helicobacter pylori Fur-regulated promoters reveals a Fur box core sequence and novel Fur-regulated genes.

    PubMed

    Pich, Oscar Q; Carpenter, Beth M; Gilbreath, Jeremy J; Merrell, D Scott

    2012-06-01

    In Helicobacter pylori, iron balance is controlled by the Ferric uptake regulator (Fur), an iron-sensing repressor protein that typically regulates expression of genes implicated in iron transport and storage. Herein, we carried out extensive analysis of Fur-regulated promoters and identified a 7-1-7 motif with dyad symmetry (5'-TAATAATnATTATTA-3'), which functions as the Fur box core sequence of H. pylori. Addition of this sequence to the promoter region of a typically non-Fur regulated gene was sufficient to impose Fur-dependent regulation in vivo. Moreover, mutation of this sequence within Fur-controlled promoters negated regulation. Analysis of the H. pylori chromosome for the occurrence of the Fur box established the existence of well-conserved Fur boxes in the promoters of numerous known Fur-regulated genes, and revealed novel putative Fur targets. Transcriptional analysis of the new candidate genes demonstrated Fur-dependent repression of HPG27_51, HPG27_52, HPG27_199, HPG27_445, HPG27_825 and HPG27_1063, as well as Fur-mediated activation of the cytotoxin associated gene A, cagA (HPG27_507). Furthermore, electrophoretic mobility shift assays confirmed specific binding of Fur to the promoters of each of these genes. Future experiments will determine whether loss of Fur regulation of any of these particular genes contributes to the defects in colonization exhibited by the H. pylori fur mutant.

  17. Inactivation of Helicobacter pylori by Chloramination

    EPA Science Inventory

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  18. Helicobacter pylori and Nonmalignant Diseases.

    PubMed

    Potamitis, Georgios S; Axon, Anthony T R

    2015-09-01

    Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.

  19. Epidemiology of Helicobacter pylori infection.

    PubMed

    Eusebi, Leonardo H; Zagari, Rocco M; Bazzoli, Franco

    2014-09-01

    Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013-March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one-third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori. However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.

  20. Fallacy of the Unique Genome: Sequence Diversity within Single Helicobacter pylori Strains.

    PubMed

    Draper, Jenny L; Hansen, Lori M; Bernick, David L; Abedrabbo, Samar; Underwood, Jason G; Kong, Nguyet; Huang, Bihua C; Weis, Allison M; Weimer, Bart C; van Vliet, Arnoud H M; Pourmand, Nader; Solnick, Jay V; Karplus, Kevin; Ottemann, Karen M

    2017-02-21

    Many bacterial genomes are highly variable but nonetheless are typically published as a single assembled genome. Experiments tracking bacterial genome evolution have not looked at the variation present at a given point in time. Here, we analyzed the mouse-passaged Helicobacter pylori strain SS1 and its parent PMSS1 to assess intra- and intergenomic variability. Using high sequence coverage depth and experimental validation, we detected extensive genome plasticity within these H. pylori isolates, including movement of the transposable element IS607, large and small inversions, multiple single nucleotide polymorphisms, and variation in cagA copy number. The cagA gene was found as 1 to 4 tandem copies located off the cag island in both SS1 and PMSS1; this copy number variation correlated with protein expression. To gain insight into the changes that occurred during mouse adaptation, we also compared SS1 and PMSS1 and observed 46 differences that were distinct from the within-genome variation. The most substantial was an insertion in cagY, which encodes a protein required for a type IV secretion system function. We detected modifications in genes coding for two proteins known to affect mouse colonization, the HpaA neuraminyllactose-binding protein and the FutB α-1,3 lipopolysaccharide (LPS) fucosyltransferase, as well as genes predicted to modulate diverse properties. In sum, our work suggests that data from consensus genome assemblies from single colonies may be misleading by failing to represent the variability present. Furthermore, we show that high-depth genomic sequencing data of a population can be analyzed to gain insight into the normal variation within bacterial strains.IMPORTANCE Although it is well known that many bacterial genomes are highly variable, it is nonetheless traditional to refer to, analyze, and publish "the genome" of a bacterial strain. Variability is usually reduced ("only sequence from a single colony"), ignored ("just publish the consensus

  1. Identification of a Latin American-specific BabA adhesin variant through whole genome sequencing of Helicobacter pylori patient isolates from Nicaragua

    SciTech Connect

    Thorell, Kaisa; Hosseini, Shaghayegh; Palacios Gonzales, Reyna Victoria Palacios; Chaotham, Chatchai; Graham, David Y.; Paszat, Lawrence; Rabeneck, Linda; Lundin, Samuel B.; Nookaew, Intawat; Sjoling, Asa

    2016-02-29

    In this study, Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk. The complete genomes of fifty-two Nicaraguan H. pylorii isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed. The Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South-and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates. In conclusion, the discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence

  2. Infection with CagA-Positive Helicobacter Pylori Strain Containing Three EPIYA C Phosphorylation Sites is Associated with More Severe Gastric Lesions in Experimentally Infected Mongolian Gerbils (Meriones Unguiculatus)

    PubMed Central

    Junior, M. Ferreira; Batista, S.A.; Vidigal, P.V.T; Cordeiro, A.A.C.; Oliveira, F.M.S.; Prata, L.O.; Diniz, A.E.T.; Barral, C.M.; Barbuto, R.C.; Comes, A.D.; Araujo, I.D.; Queiroz, D.M.M.; Caliari, M.V.

    2015-01-01

    Infection with Helicobacter pylori strains containing high number of EPIYA-C phosphorylation sites in the CagA is associated with significant gastritis and increased risk of developing pre-malignant gastric lesions and gastric carcinoma. However, these findings have not been reproduced in animal models yet. Therefore, we investigated the effect on the gastric mucosa of Mongolian gerbil (Meriones unguiculatus) infected with CagA-positive H. pylori strains exhibiting one or three EPIYA-C phosphorilation sites. Mongolian gerbils were inoculated with H. pylori clonal isolates containing one or three EPIYA-C phosphorylation sites. Control group was composed by uninfected animals challenged with Brucella broth alone. Gastric fragments were evaluated by the modified Sydney System and digital morphometry. Clonal relatedness between the isolates was considered by the identical RAPD-PCR profiles and sequencing of five housekeeping genes, vacA i/d region and of oipA. The other virulence markers were present in both isolates (vacA s1i1d1m1, iceA2, and intact dupA). CagA of both isolates was translocated and phosphorylated in AGS cells. After 45 days of infection, there was a significant increase in the number of inflammatory cells and in the area of the lamina propria in the infected animals, notably in those infected by the CagA-positive strain with three EPIYA-C phosphorylation sites. After six months of infection, a high number of EPIYA-C phosphorylation sites was associated with progressive increase in the intensity of gastritis and in the area of the lamina propria. Atrophy, intestinal metaplasia, and dysplasia were also observed more frequently in animals infected with the CagA-positive isolate with three EPIYA-C sites. We conclude that infection with H. pylori strain carrying a high number of CagA EPIYA-C phosphorylation sites is associated with more severe gastric lesions in an animal model of H. pylori infection. PMID:26150158

  3. Helicobacter pylori and nonmalignant diseases.

    PubMed

    Ierardi, Enzo; Goni, Elisabetta; Losurdo, Giuseppe; Di Mario, Francesco

    2014-09-01

    Peptic ulcer bleeding and recurrence rate are strongly linked to Helicobacter pylori infection even if nonsteroidal anti-inflammatory drugs (NSAIDs) play a relevant role in this setting. Further studies confirm that H. pylori eradication lowers the risk of recurrent peptic ulcer bleeding. Therefore, a test-and-treat strategy appears to be mandatory for patients with a history of ulcer bleeding and NSAIDs and/or aspirin use. Concerning gastroesophageal reflux disease (GERD), evidence clearly shows that H. pylori status has no effect on symptoms and treatment. Therefore, H. pylori treatment is not contraindicated in patients with GERD. The exact role of H. pylori in functional dyspepsia (FD) remains controversial. Novel possible mechanisms by which H. pylori may elicit dyspeptic symptoms include alterations of gastric motility, as well as endocrine and acid-secretory abnormalities. Hunger sensations, acid secretion, and gastrointestinal motility are regulated by ghrelin, particularly produced by the gastric enteroendocrine cell compartment. The improvement of symptoms correlates with enhanced plasma ghrelin levels. Apart from the need for more trials on this topic, these findings may give insight into the underlying pathophysiology of FD symptoms. Recent reports suggest that the presence of bacterial DNA in the oral cavity may be relevant to its transmission. A potential protective role of H. pylori on inflammatory bowel diseases needs to be better elucidated.

  4. Analysis of the intactness of Helicobacter pylori cag pathogenicity island in Iranian strains by a new PCR-based strategy and its relationship with virulence genotypes and EPIYA motifs.

    PubMed

    Yadegar, Abbas; Alebouyeh, Masoud; Zali, Mohammad Reza

    2015-10-01

    Variants of the Helicobacter pylori cag pathogenicity island (cagPAI) and certain virulence genotypes have been proposed to be associated with different gastric disorders. In the present study, we designed a new PCR-based strategy to investigate the intactness of cagPAI in Iranian patients using highly specific primer sets spanning the cagPAI region. The possible relationship between the cagPAI status of the strains and clinical outcomes was also determined. We also characterized virulence genotypes (cagL, cagA, vacA, babA2 and sabA) and variants of CagA EPIYA motifs in these strains. H. pylori was detected in 61 out of 126 patients with various gastroduodenal diseases. The cagL, cagA, vacA s1m1, vacA s1m2, vacA s2m2, babA2, and sabA genotypes were detected in 96.7%, 85.2%, 29.5%, 45.9%, 24.6%, 96.7%, and 83.6% of the strains, respectively. Among the 52 cagA-positive strains, EPIYA motifs ABC, ABCC, ABCCC, and mixed types were orderly detected in the 39, 7, 1, and 5 strains. The cagPAI positivity included both intact and partially deleted, with the overall frequencies of 70.5% and 26.2%, respectively. The majority of the strains from patients with PUD (87.5%), gastric erosion (83.3%) and cancer (80%) presented an intact cagPAI, while a lower frequency of cagPAI intactness was detected in gastritis patients (61.1%). However, no significant relationship was found between the possession of intact cagPAI and clinical outcomes. Furthermore, we found that cagA and vacA s1m1 genotypes were significantly correlated with intact cagPAI (P=0.015 and P=0.012). A significant correlation was also found between EPIYA-ABC and intact cagPAI (P=0.010). The proposed PCR-based scheme was found to be useful for determining the intactness of cagPAI. Our findings also indicate that the cagPAI appears to be intact and rather conserved in majority of Iranian strains. Finally, our study proposed that H. pylori strains with partially deleted cagPAI were less likely to cause severe diseases

  5. Helicobacter pylori in lacrimal secretions.

    PubMed

    Batioglu-Karaaltin, Aysegul; Saatci, Ozlem; Akpinar, Meltem; Celik, Melih Ozgür; Develioglu, Omer; Yigit, Ozgur; Külekçi, Mehmet; Akarsubaşı, Alper Tunga

    2016-03-01

    The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy-negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions.

  6. Endoscopic transmission of Helicobacter pylori.

    PubMed

    Tytgat, G N

    1995-01-01

    The contamination of endoscopes and biopsy forceps with Helicobacter pylori occurs readily after endoscopic examination of H. pylori-positive patients. Unequivocal proof of iatrogenic transmission of the organism has been provided. Estimates for transmission frequency approximate to 4 per 1000 endoscopies when the infection rate in the endoscoped population is about 60%. Iatrogenic transmission has also been shown to be the cause of the so-called 'acute mucosal lesion' syndrome in Japan. Traditional cleaning and alcohol rinsing is insufficient to eliminate endoscope/forceps contamination. Only meticulous adherence to disinfection recommendations guarantees H. pylori elimination.

  7. [Helicobacter pylori -- 2014].

    PubMed

    Buzás, György Miklós

    2015-02-08

    The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.

  8. Comparative Genomics of a Helicobacter pylori Isolate from a Chinese Yunnan Naxi Ethnic Aborigine Suggests High Genetic Divergence and Phage Insertion

    PubMed Central

    You, Yuanhai; He, Lihua; Zhang, Maojun; Zhang, Jianzhong

    2015-01-01

    Helicobacter pylori is a common pathogen correlated with several severe digestive diseases. It has been reported that isolates associated with different geographic areas, different diseases and different individuals might have variable genomic features. Here, we describe draft genomic sequences of H. pylori strains YN4-84 and YN1-91 isolated from patients with gastritis from the Naxi and Han populations of Yunnan, China, respectively. The draft sequences were compared to 45 other publically available genomes, and a total of 1059 core genes were identified. Genes involved in restriction modification systems, type four secretion system three (TFS3) and type four secretion system four (TFS4), were identified as highly divergent. Both YN4-84 and YN1-91 harbor intact cag pathogenicity island (cagPAI) and have EPIYA-A/B/D type at the carboxyl terminal of cagA. The vacA gene type is s1m2i1. Another major finding was a 32.5-kb prophage integrated in the YN4-84 genome. The prophage shares most of its genes (30/33) with Helicobacter pylori prophage KHP30. Moreover, a 1,886 bp transposable sequence (IS605) was found in the prophage. Our results imply that the Naxi ethnic minority isolate YN4-84 and Han isolate YN1-91 belong to the hspEAsia subgroup and have diverse genome structure. The genome has been extensively modified in several regions involved in horizontal DNA transfer. The important roles played by phages in the ecology and microevolution of H. pylori were further emphasized. The current data will provide valuable information regarding the H. pylori genome based on historic human migrations and population structure. PMID:25799515

  9. Identification of a Latin American-specific BabA adhesin variant through whole genome sequencing of Helicobacter pylori patient isolates from Nicaragua

    DOE PAGES

    Thorell, Kaisa; Hosseini, Shaghayegh; Palacios Gonzales, Reyna Victoria Palacios; ...

    2016-02-29

    In this study, Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk. The complete genomes ofmore » fifty-two Nicaraguan H. pylorii isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed. The Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South-and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates. In conclusion, the discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence properties.« less

  10. Non-pharmacological treatment of Helicobacter pylori

    PubMed Central

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-01-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  11. Which test to use to detect Helicobacter pylori infection in patients with low-grade gastric mucosa-associated lymphoid tissue lymphoma?

    PubMed

    Lehours, Philippe; Ruskone-Fourmestraux, Agnès; Lavergne, Anne; Cantet, Franck; Mégraud, Francis

    2003-02-01

    Helicobacter pylori is involved in the pathogenesis of lymphoma of the gastric mucosa-associated lymphoid tissue (MALT). Because gastric MALT lymphoma is a rare disease, few studies comparing the accuracy of diagnostic tests in this group of patients have been carried out, and only a limited number of tests (essentially histological) were performed. The aim of our study was to compare the results of four different diagnostic methods used to detect H. pylori (histology, culture, polymerase chain reaction, and serology) in a prospective multicenter study. A patient was considered to be H. pylori positive if culture or histology was positive. During the period 1995-2000, a total of 90 patients with low-grade gastric MALT lymphoma were enrolled. Results for the four tests were available for 56 patients (62.2%). Among these patients, the four tests were concordant in 35 cases (62.5%), i.e., were positive in 19 cases (33.9%) and negative in 16 patients (17.8%). Histology (39/40 positive, 97.5%) and serology (38/40 positive, 95.0%) were the most sensitive tests. Polymerase chain reaction (PCR) and culture were positive in 52.5% and 50%, respectively. The cagA gene was detected in 47.4% of the strains.

  12. Helicobacter pylori-Mediated Protection from Allergy Is Associated with IL-10-Secreting Peripheral Blood Regulatory T Cells

    PubMed Central

    Hussain, Khiyam; Letley, Darren P.; Greenaway, A. Borgel; Kenefeck, Rupert; Winter, Jody A.; Tomlinson, William; Rhead, Joanne; Staples, Emily; Kaneko, Kazuyo; Atherton, John C.; Robinson, Karen

    2016-01-01

    Helicobacter pylori infections are usually established in early childhood and continuously stimulate immunity, including T-helper 1 (Th1), Th17, and regulatory T-cell (Treg) responses, throughout life. Although known to be the major cause of peptic ulcer disease and gastric cancer, disease occurs in a minority of those who are infected. Recently, there has been much interest in beneficial effects arising from infection with this pathogen. Published data robustly show that the infection is protective against asthma in mouse models. Epidemiological studies show that H. pylori is inversely associated with human allergy and asthma, but there is a paucity of mechanistic data to explain this. Since Th1 and Treg responses are reported to protect against allergic responses, we investigated if there were links between the human systemic Th1 and Treg response to H. pylori and allergen-specific IgE levels. The human cytokine and T-cell responses were examined using peripheral blood mononuclear cells (PBMCs) from 49 infected and 58 uninfected adult patients. Concentrations of total and allergen-specific plasma IgE were determined by ELISA and ImmunoCAP assays. These responses were analyzed according to major virulence factor genotypes of the patients’ colonizing H. pylori strains. An in vitro assay was employed, using PBMCs from infected and uninfected donors, to determine the role of Treg cytokines in the suppression of IgE. Significantly higher frequencies of IL-10-secreting CD4+CD25hi Tregs, but not H. pylori-specific Th1 cells, were present in the peripheral blood of infected patients. Total and allergen-specific IgE concentrations were lower when there was a strong Treg response, and blocking IL-10 in vitro dramatically restored IgE responses. IgE concentrations were also significantly lower when patients were infected with CagA+ strains or those expressing the more active i1 form of VacA. The systemic IL-10+ Treg response is therefore likely to play a role in H. pylori

  13. Composition and Gene Expression of the cag Pathogenicity Island in Helicobacter pylori Strains Isolated from Gastric Carcinoma and Gastritis Patients in Costa Rica

    PubMed Central

    Occhialini, Alessandra; Marais, Armelle; Urdaci, Maria; Sierra, Rafaela; Muñoz, Nubia; Covacci, Antonello; Mégraud, Francis

    2001-01-01

    The composition and in vitro expression of the cag pathogenicity island genes in a group of Helicobacter pylori strains obtained from patients suffering from chronic gastritis-associated dyspepsia (n = 26) or gastric carcinoma (n = 17) were analyzed. No significant difference in the distribution of the 10 studied regions was found between the cases and the controls. Nine strains did not harbor any of the selected regions: eight (30.8%) isolated from patients with gastritis only and one (5.9%) from a patient with gastric carcinoma. No association was found between the number of repeated sequences at the 3′ end of the cagA gene or the presence of tyrosine phosphorylation motifs and the clinical origin of the strains. The virB10 homolog gene was the sole gene studied to be significantly expressed more often in cancer strains than in gastritis strains (P = 0.03). PMID:11179371

  14. Composition and gene expression of the cag pathogenicity island in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica.

    PubMed

    Occhialini, A; Marais, A; Urdaci, M; Sierra, R; Muñoz, N; Covacci, A; Mégraud, F

    2001-03-01

    The composition and in vitro expression of the cag pathogenicity island genes in a group of Helicobacter pylori strains obtained from patients suffering from chronic gastritis-associated dyspepsia (n = 26) or gastric carcinoma (n = 17) were analyzed. No significant difference in the distribution of the 10 studied regions was found between the cases and the controls. Nine strains did not harbor any of the selected regions: eight (30.8%) isolated from patients with gastritis only and one (5.9%) from a patient with gastric carcinoma. No association was found between the number of repeated sequences at the 3' end of the cagA gene or the presence of tyrosine phosphorylation motifs and the clinical origin of the strains. The virB10 homolog gene was the sole gene studied to be significantly expressed more often in cancer strains than in gastritis strains (P = 0.03).

  15. Epidemiology of Helicobacter pylori infection.

    PubMed

    Leja, Mārcis; Axon, Anthony; Brenner, Hermann

    2016-09-01

    This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal-oral transmission and the use of well-water and other unpurified water. Finally, the long-term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.

  16. Helicobacter pylori infection and skin disorders.

    PubMed

    Kutlubay, Zekayi; Zara, Tuba; Engin, Burhan; Serdaroğlu, Server; Tüzün, Yalçin; Yilmaz, Erkan; Eren, Bülent

    2014-08-01

    Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of Helicobacter pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, neurological, metabolic, autoimmune, and dermatological diseases. Some studies suggest an association between Helicobacter pylori infection and skin diseases such as chronic idiopathic urticaria and rosacea. There have also been few case reports documenting association between Helicobacter pylori and psoriasis vulgaris, Behçet's disease, alopecia areata, Henoch-Schönlein purpura, and Sweet's syndrome. However, more systematic studies are required to clarify the proposed association between Helicobacter pylori and skin diseases; most of the studies do not show relevant relationships of these diseases with Helicobacter pylori infections. This review discusses skin diseases that are believed to be associated with Helicobacter pylori.

  17. Comparison of PCR with other diagnostic techniques for the detection of H. pylori infection in patients presenting with gastroduodenal symptons in Nigeria

    PubMed Central

    Smith, Stella I; Fowora, Muinah A; Otegbayo, Jesse A; Abdulkareem, Fatimah B; Omonigbehin, Emmanuel A; Adegboyega, Akere; Contreras, Monica; Haas, Rainer

    2011-01-01

    The study was aimed at comparing PCR methods of direct detection from biopsy using the boiling method and one other method with two known gold standards (histology and CLO test) for the diagnosis of H. pylori in Nigeria. A total of 168 biopsies (three from antrum and one from corpus each) were taken from 42 patients presenting with various gastroduodenal symptons after informed consent was obtained from them.The biopsies were analysed using the CLO test kit and histology, while the boiling method as described by Holmes and Quigley (1981) was used to obtain DNA and then PCR using the 16S rRNA gene, glmM gene and cagA gene. With CLO test 15/42 (35.71%) were positive, histology 13/42 (30.95%) were positive, 16S rRNA 22/42 (52.38%) were positive, glmM 19/42 (45.24%) were positive, cagA 19/42 (45.24%) were positive. The sensitivity and specificity of the PCR tests with CLO as the gold standard showed that the tests were 100% sensitive and varied between 74.1% to 84.1% in specificity. The PPV and NPV showed that the NPV was almost 100%, while the PPV was between 68.2% and 75%. Using the histology as the gold standard, the sensitivity was almost 100% while the specificity, the PPV were reduced in comparison to the CLO test. The PCR test using the glmM gene appears to be the most reliable test for diagnosis of H. pylori in Nigeria most especially where culture is difficult due to the power outages. PMID:21686132

  18. Diet and Helicobacter pylori infection

    PubMed Central

    Imiela, Jacek

    2016-01-01

    Helicobacter pylori infection has accompanied man for thousands of years. In some infected patients, a complex and dynamic pathogen-host reaction triggers pathogenic pathways resulting in development, inter alia, of atrophic gastritis, peptic ulcer disease (both gastric and duodenal), gastric adenocarcinoma, and MALT lymphoma. Large-scale eradication therapy is associated with a rapid increase in antibiotic resistance, gut flora composition disturbances, and increased risk of development, inter alia, of paediatric infectious diarrhoeas, atopic diseases, and oesophageal adenocarcinoma. Our diet contains many substances with potent antibacterial activity against H. pylori. Dietary interventions enable a decrease in H. pylori colonisation and result in a decrease in gastritis prevalence, thus potentially lowering the risk of gastric adenocarcinoma development. PMID:27713775

  19. Genetic Manipulation of a Naturally Competent Bacterium, Helicobacter pylori

    PubMed Central

    Noto, Jennifer M.; Peek, Richard M.

    2013-01-01

    Genetic manipulation of Helicobacter pylori facilitates characterization and functional analysis of individual H. pylori genes. This chapter discusses the methods involved in H. pylori chromosomal DNA isolation, mutagenesis of individual genes, and natural transformation. PMID:23015491

  20. Increased Helicobacter pylori-associated Gastric Cancer Risk in the Andean Region of Colombia Is Mediated by Spermine Oxidase

    PubMed Central

    Chaturvedi, Rupesh; de Sablet, Thibaut; Asim, Mohammad; Piazuelo, M. Blanca; Barry, Daniel P.; Verriere, Thomas G.; Sierra, J. Carolina; Hardbower, Dana M.; Delgado, Alberto G.; Schneider, Barbara G.; Israel, Dawn A.; Romero-Gallo, Judith; Nagy, Toni A.; Morgan, Douglas R.; Murray-Stewart, Tracy; Bravo, Luis E.; Peek, Richard M.; Fox, James G.; Woster, Patrick M.; Casero, Robert A.; Correa, Pelayo; Wilson, Keith T.

    2014-01-01

    Helicobacter pylori infection causes gastric cancer, the third leading cause of cancer death worldwide. More than half of the world’s population is infected, making universal eradication impractical. Clinical trials suggest that antibiotic treatment only reduces gastric cancer risk in patients with non-atrophic gastritis (NAG), and is ineffective once preneoplastic lesions of multifocal atrophic gastritis (MAG) and intestinal metaplasia (IM) have occurred. Therefore, additional strategies for risk stratification and chemoprevention of gastric cancer are needed. We have implicated polyamines, generated by the rate limiting enzyme ornithine decarboxylase (ODC), in gastric carcinogenesis. During H. pylori infection, the enzyme spermine oxidase (SMOX) is induced, which generates hydrogen peroxide from the catabolism of the polyamine spermine. Herein, we assessed the role of SMOX in the increased gastric cancer risk in Colombia associated with the Andean mountain region when compared to the low risk region on the Pacific coast. When co-cultured with gastric epithelial cells, clinical strains of H. pylori from the high risk region induced more SMOX expression and oxidative DNA damage, and less apoptosis than low risk strains. These findings were not attributable to differences in the CagA oncoprotein. Gastric tissues from subjects from the high risk region exhibited greater levels of SMOX and oxidative DNA damage by immunohistochemistry and flow cytometry, and this occurred in NAG, MAG, and IM. In Mongolian gerbils, a prototype colonizing strain from the high risk region induced more SMOX, DNA damage, dysplasia and adenocarcinoma than a colonizing strain from the low risk region. Treatment of gerbils with either α-difluoromethylornithine (DFMO), an inhibitor of ODC, or MDL 72527, an inhibitor of SMOX, reduced gastric dysplasia and carcinoma, as well as apoptosis-resistant cells with DNA damage. These data indicate that aberrant activation of polyamine-driven oxidative

  1. Antibiotics resistance of Helicobacter pylori and treatment modalities in children with H. pylori infection.

    PubMed

    Seo, Ji-Hyun; Woo, Hyang-Ok; Youn, Hee-Shang; Rhee, Kwang-Ho

    2014-02-01

    Pediatric infection with Helicobacter pylori may occur early in childhood and persist lifelong. Global pediatric clinical studies have reported a decreasing tendency in the overall rate of H. pylori eradication. In pediatric patients with H. pylori infection, pediatric patients with peptic ulcer, and the first-degree relatives of patients with a history of gastric cancer, it is commonly recommended that H. pylori strains be eradicated. Antibiotic drug resistance to H. pylori, which has been reported to vary widely between geographic regions, is mainly associated with treatment failure in these patients. It is therefore imperative that the antibiotic resistance rates of H. pylori in children and adolescents be meticulously monitored across countries and throughout geographic regions. This paper particularly focuses on the antibiotic drug resistance of H. pylori and the thearpy of pediatric H. pylori infection cases.

  2. Helicobacter pylori: Friend or foe?

    PubMed Central

    Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob

    2014-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world’s population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is “anyone with a fear of gastric cancer” which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection. PMID:25083071

  3. Helicobacter pylori: friend or foe?

    PubMed

    Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob

    2014-07-21

    Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

  4. Toxicosis in Helicobacter Pylori infection - a hypothesis

    PubMed Central

    BELASCU, MIHAI

    2013-01-01

    Background and aim We present a new clinical entity in relation to the Helicobacter pylori infection characterized by complex and varied clinical extra-digestive manifestations. Clinical findings such as asthenia, adynamia, sleep disorders, hair and nails modifications, digestive symptoms and heart rhythm disorders describe the clinical aspect of toxicosis associated with Helicobacter pylori infection. Methods The clinical presentation and therapy of patients with Helicobacter pylori infection were analyzed. Results Combined drug therapy: antibiotics + proton pump inhibitors + colloidal bismuth compound determinate remission of the symptoms in the first 3 to 5 days. The characteristic of the relation between Helicobacter pylori and the mucus-epithelial cell complex, the properties of the bacterial cell components, and the inflammatory and immunological response targeting other organs describe the immuno-pathological outbreak of Helicobacter pylori. Conclusion We support the term of toxicosis associated with Helicobacter pylori infection in selected cases. PMID:26527950

  5. 3rd Brazilian Consensus on Helicobacter pylori.

    PubMed

    Coelho, Luiz Gonzaga; Maguinilk, Ismael; Zaterka, Schlioma; Parente, José Miguel; do Carmo Friche Passos, Maria; Moraes-Filho, Joaquim Prado P

    2013-04-01

    Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  6. Immune responses to Helicobacter pylori infection

    PubMed Central

    Moyat, Mati; Velin, Dominique

    2014-01-01

    Helicobacter pylori (H. pylori) infection is one of the most common infections in human beings worldwide. H. pylori express lipopolysaccharides and flagellin that do not activate efficiently Toll-like receptors and express dedicated effectors, such as γ-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase, that actively induce tolerogenic signals. In this perspective, H. pylori can be considered as a commensal bacteria belonging to the stomach microbiota. However, when present in the stomach, H. pylori reduce the overall diversity of the gastric microbiota and promote gastric inflammation by inducing Nod1-dependent pro-inflammatory program and by activating neutrophils through the production of a neutrophil activating protein. The maintenance of a chronic inflammation in the gastric mucosa and the direct action of virulence factors (vacA and cytotoxin-associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H. pylori cannot be considered as symbiotic bacteria but rather as part of the pathobiont. The development of a H. pylori vaccine will bring health benefits for individuals infected with antibiotic resistant H. pylori strains and population of underdeveloped countries. PMID:24914318

  7. Oral Helicobacter pylori, its relationship to successful eradication of gastric H. pylori and saliva culture confirmation.

    PubMed

    Wang, X M; Yee, K C; Hazeki-Taylor, N; Li, J; Fu, H Y; Huang, M L; Zhang, G Y

    2014-08-01

    The present study was designed to explore the existence of oral Helicobacter pylori (H. pylori), its relationship in the oral cavity to the success rate of eradication of the gastric H. pylori infection, and to determine if the mouthwash solution contained lysine (0.4%) and glycerol monolaurate (0.2%) (LGM) could eliminate oral H. pylori, as well as using the saliva H. pylori culture to confirm the existence of oral H. pylori. A total of 159 symptomatic individuals with stomach pain and 118 asymptomatic individuals with no stomach complaints, were recruited and tested using the saliva H. pylori antigen test (HPS), the H. pylori flagellin test (HPF), the urea breath test (UBT C(13)) and the polymerase chain reaction (PCR) test, which tests were also confirmed by saliva culture. The test subjects also received various treatments. It was found that the H. pylori antigen exists in the oral cavity in UBT C(13) negative individuals. Traditional treatment for gastric eradication had only a 10.67 percent (10.67%) effectiveness rate on the oral H. pylori infection. In groups of patients with the oral H. pylori infection, but with negative UBT C(13), a mouthwash solution provided a 72.58% effectiveness rate in the 95% of the confidence interval (CI) ranges on the oral H. pylori infection. Traditional drug gastric eradication and teeth cleaning (TC) had less than a 10% effectiveness rate. Treatment of the oral infection increased the success rate of eradication of the stomach infection from 61.33% to 82.26% in the 95% CI ranges. We concluded that the successful rate of eradication of gastric H. pylori bears a significant relationship to the oral infection from H. pylori.

  8. Helicobacter pylori colonization of the oral cavity: A milestone discovery

    PubMed Central

    Yee, John KC

    2016-01-01

    Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization. PMID:26811613

  9. Helicobacter pylori colonization of the oral cavity: A milestone discovery.

    PubMed

    Yee, John K C

    2016-01-14

    Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization.

  10. Systematic site-directed mutagenesis of the Helicobacter pylori CagL protein of the Cag type IV secretion system identifies novel functional domains

    PubMed Central

    Bönig, Tobias; Olbermann, Patrick; Bats, Simon H.; Fischer, Wolfgang; Josenhans, Christine

    2016-01-01

    The Cag Type IV secretion system, which contributes to inflammation and cancerogenesis during chronic infection, is one of the major virulence factors of the bacterial gastric pathogen Helicobacter pylori. We have generated and characterized a series of non-marked site-directed chromosomal mutants in H. pylori to define domains of unknown function of the essential tip protein CagL of the Cag secretion system. Characterizing the CagL mutants, we determined that their function to activate cells and transport the effector CagA was reduced to different extents. We identified three novel regions of the CagL protein, involved in its structural integrity, its possible interaction with the CagPAI T4SS pilus protein CagI, and in its binding to integrins and other host cell ligands. In particular two novel variable CagL motifs were involved in integrin binding, TSPSA, and TASLI, which is located opposite of its integrin binding motif RGD. We thereby defined functionally important subdomains within the CagL structure, which can be used to clarify CagL contributions in the context of other CagPAI proteins or for inhibition of the CagT4SS. This structure-function correlation of CagL domains can also be instructive for the functional characterization of other potential VirB5 orthologs whose structure is not yet known. PMID:27922023

  11. Cag-delta (Cag3) protein from the Helicobacter pylori 26695 cag type IV secretion system forms ring-like supramolecular assemblies.

    PubMed

    Smart, Jonathan; Fouillen, Aurélien; Casu, Bastien; Nanci, Antonio; Baron, Christian

    2017-01-01

    Helicobacter pylori is an important cause of gastric pathologies and persistent infection can lead to stomach cancer. Virulent H. pylori strains encode a type IV secretion system responsible for translocation of the oncogenic CagA protein into cells of the gastric mucosa. Gene HP0522 encodes the essential component Cagδ (Cag3), and we show by gel filtration and cross-linking that purified Cagδ forms high molecular mass complexes. In contrast, its interaction partner CagT is mostly monomeric, but co-fractionates after gel filtration. Analysis by transmission electron microscopy revealed that purified Cagδ complexes can self-assemble ring-like structures. Cagδ-overexpressing Escherichia coli exhibits membrane-associated circular profiles in regions of the cell envelope with intense immunogold labelling with a Cagδ-specific antiserum. Our results suggest that Cagδ has the capacity to form macromolecular structures contributing to the assembly of the type IV secretion system.

  12. Clinicopathological characteristics of invasive gastric Helicobacter pylori.

    PubMed

    Dudley, Jonathan; Wieczorek, Tad; Selig, Martin; Cheung, Hoiwan; Shen, Jeanne; Odze, Robert; Deshpande, Vikram; Zukerberg, Lawrence

    2017-03-01

    Helicobacter pylori organisms have been observed deep within the stomach mucosa with an "intracellular" appearance, although the clinicopathological characteristics of such cases remain poorly understood. We analyzed 18 cases of deep mucosal H pylori and associated clinical (sex, age, history of H pylori infection, or proton pump inhibitor [PPI] use, medications, smoking, alcohol use, comorbidities, treatment response) and pathological (presence of lymphoid aggregates, intestinal metaplasia, PPI effect, active and/or chronic inflammation, quantity of invasive versus surface H pylori) characteristics. Electron microscopy was performed on 6 cases with the highest burden of invasive H pylori. Within our sample, 3 of 16 had a history of H pylori infection, 10 of 15 were receiving PPIs at the time of biopsy, and 12 of 13 had a negative posttreatment follow-up. Histology revealed that invasive H pylori were more commonly associated with chronic inflammation, in both the antrum (15/15 chronic, 8/15 acute) and fundus (17/18 chronic, 8/18 acute). Electron microscopy showed organisms within intercellular and luminal spaces, but no intracellular organisms. Deep mucosal H pylori often have an intracellular appearance but are contained within intercellular and luminal spaces and are responsive to standard therapy.

  13. Are probiotics useful in Helicobacter pylori eradication?

    PubMed Central

    Homan, Matjaž; Orel, Rok

    2015-01-01

    Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects. PMID:26457024

  14. Helicobacter pylori and non-malignant diseases.

    PubMed

    Furuta, Takahisa; Delchier, Jean-Charles

    2009-09-01

    It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.

  15. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer.

  16. Construction of a Helicobacter pylori-Escherichia coli shuttle vector for gene transfer in Helicobacter pylori.

    PubMed Central

    Lee, W K; An, Y S; Kim, K H; Kim, S H; Song, J Y; Ryu, B D; Choi, Y J; Yoon, Y H; Baik, S C; Rhee, K H; Cho, M J

    1997-01-01

    In this study, a Helicobacter pylori-Escherichia coli shuttle vector was constructed for transferring DNA into H. pylori. The smallest cryptic plasmid (1.2 kb), pHP489, among those harbored by 77 H. pylori isolates was selected as a base replicon for constructing vectors. HindIII-digested pHP489 was ligated with a kanamycin resistance gene [aph(3')-III], which originated from Campylobacter jejuni, to produce the recombinant plasmid pHP489K. pHP489K was efficiently transformed into and stably maintained in H. pylori strains. The shuttle vector pBHP489K (3.6 kb) was constructed by the recombination of pHP489, ColE1, and aph(3')-III sequences. pBHP489K was reciprocally transformed into and maintained in both H. pylori and E. coli. Introduction of the shuttle vector clone DNA (pBHP489K/AB; 6.7 kb), containing the ureA and ureB genes of H. pylori, into urease-negative mutants of H. pylori led to the restoration of their urease activity. The transformants were confirmed to contain the incoming plasmid DNA. pBHP489K satisfied the requirements for an H. pylori-E. coli shuttle vector, implying that it might be a useful vector for investigating pathogenicity and restriction-modification systems of H. pylori. PMID:9406406

  17. Recurrent aphthous stomatitis and Helicobacter pylori

    PubMed Central

    Gomes, Carolina-Cavaliéri; Gomez, Ricardo-Santiago; Zina, Lívia-Guimarães

    2016-01-01

    Background Recurrent aphthous stomatitis (RAS) is a recurrent painful ulcerative disorder that commonly affects the oral mucosa. Local and systemic factors such as trauma, food sensitivity, nutritional deficiencies, systemic conditions, immunological disorders and genetic polymorphisms are associated with the development of the disease. Helicobacter pylori (H. pylori) is a gram-negative, microaerophile bacteria, that colonizes the gastric mucosa and it was previously suggested to be involved in RAS development. In the present paper we reviewed all previous studies that investigated the association between RAS and H. pylori. Material and Methods A search in Pubmed (MEDLINE) databases was made of articles published up until July 2015 using the following keywords: Helicobacter Pylori or H. pylori and RAS or Recurrent aphthous stomatitis. Results Fifteen experimental studies that addressed the relationship between infection with H. pylori and the presence of RAS and three reviews, including a systematic review and a meta-analysis were included in this review. The studies reviewed used different methods to assess this relationship, including PCR, nested PCR, culture, ELISA and urea breath test. A large variation in the number of patients included in each study, as well as inclusion criteria and laboratorial methods was observed. H. pylori can be detected in the oral mucosa or ulcerated lesion of some patients with RAS. The quality of the all studies included in this review was assessed using levels of evidence based on the University of Oxford’s Center for Evidence Based Medicine Criteria. Conclusions Although the eradication of the infection may affect the clinical course of the oral lesions by undetermined mechanisms, RAS ulcers are not associated with the presence of the bacteria in the oral cavity and there is no evidence that H. pylori infection drives RAS development. Key words:Campylobacter, elisa, h. pylori, Helicobacter Pylori, RAS, recurrent aphthous

  18. Helicobacter pylori as an oncogenic pathogen, revisited.

    PubMed

    Miftahussurur, Muhammad; Yamaoka, Yoshio; Graham, David Y

    2017-03-21

    Gastric cancer is an inflammation-associated malignancy aetiologically related to infection with the bacterium, Helicobacter pylori, which is considered a necessary but insufficient cause. Unless treated, H. pylori causes life-long acute and chronic gastric inflammation resulting in progressive gastric mucosal damage that may result in gastric cancer. The rate of progression from superficial gastritis, to an atrophic metaplastic mucosa, and ultimately to cancer relates to the virulence of the infecting H. pylori as well as host and environmental factors. H. pylori virulence is a reflection of its propensity to cause severe gastric inflammation. Both mucosal inflammation and H. pylori can cause host genomic instability, including dysregulation of DNA mismatch repair, stimulation of expression of activation-induced cytidine deaminase, abnormal DNA methylation and dysregulation of  micro RNAs, which may result in an accumulation of mutations and loss of normal regulation of cell growth. The difference in cancer risk between the most and least virulent H. pylori strain is only approximately 2-fold. Overall, none of the putative virulence factors identified to date have proved to be disease-specific. The presence, severity, extent and duration of inflammation appear to be the most important factors and current evidence suggests that any host, environmental or bacterial factor that reliably enhances the inflammatory response to the H. pylori infection increases the risk of gastric cancer.

  19. Metalloregulation of Helicobacter pylori physiology and pathogenesis

    PubMed Central

    Haley, Kathryn P.; Gaddy, Jennifer A.

    2015-01-01

    Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes over half of the world's population. Chronic H. pylori infection is associated with increased risk for numerous disease outcomes including gastritis, dysplasia, neoplasia, B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma), and invasive adenocarcinoma. The complex interactions that occur between pathogen and host are dynamic and exquisitely regulated, and the relationship between H. pylori and its human host are no exception. To successfully colonize, and subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors to subvert the host's innate and adaptive immune response. H. pylori achieves this precise gene regulation by sensing subtle environmental changes including host-mediated alterations in nutrient availability and responding with dramatic global changes in gene expression. Recent studies revealed that the presence or absence of numerous metal ions encountered in the lumen of the stomach, or within host tissues, including nickel, iron, copper and zinc, can influence regulatory networks to alter gene expression in H. pylori. These expression changes modulate the deployment of bacterial virulence factors that can ultimately influence disease outcome. In this review we will discuss the environmental stimuli that are detected by H. pylori as well as the trans regulatory elements, specifically the transcription regulators and transcription factors, that allow for these significant transcriptional shifts. PMID:26388855

  20. Hematologic manifestations of Helicobacter pylori infection

    PubMed Central

    Campuzano-Maya, Germán

    2014-01-01

    Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680

  1. Acetaldehyde and ethanol production by Helicobacter pylori.

    PubMed

    Salmela, K S; Roine, R P; Höök-Nikanne, J; Kosunen, T U; Salaspuro, M

    1994-04-01

    By virtue of possessing alcohol dehydrogenase activity, cytosol prepared from Helicobacter pylori produces toxic acetaldehyde from ethanol in vitro. To approach the in vivo situation in the stomach, we have now investigation whether intact H. pylori--without addition of exogenous nicotinamide adenine dinucleotide--also forms acetaldehyde. Furthermore, to assess the energy metabolism of H. pylori, we determined whether the alcohol dehydrogenase-catalyzed reaction can run in the opposite direction with ethanol as the end-product and thereby yield energy for the organism. Intact H. pylori formed acetaldehyde already at low ethanol concentrations (at 0.5% ethanol, acetaldehyde, 64 +/- 21 and 75 +/- 9 mumol/l (mean +/- SEM) for strains NCTC 11637 and NCTC 11638, respectively). H. pylori produced ethanol in concentrations that can be significant for the energy metabolism of the organism. Acetaldehyde production by H. pylori may be an important factor in the pathogenesis of gastroduodenal diseases associated with the organism. The primary function of H. pylori alcohol dehydrogenase may, however, be alcoholic fermentation and consequent energy production under microaerobic conditions.

  2. Helicobacter pylori and gastric cancer: Indian enigma.

    PubMed

    Misra, Vatsala; Pandey, Renu; Misra, Sri Prakash; Dwivedi, Manisha

    2014-02-14

    Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.

  3. Vaccine against Helicobacter pylori: Inevitable approach

    PubMed Central

    Talebi Bezmin Abadi, Amin

    2016-01-01

    Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium. PMID:27003991

  4. Vaccine against Helicobacter pylori: Inevitable approach.

    PubMed

    Talebi Bezmin Abadi, Amin

    2016-03-21

    Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.

  5. Helicobacter pylori Adhesion to Carbohydrates

    PubMed Central

    Aspholm, Marina; Kalia, Awdhesh; Ruhl, Stefan; Schedin, Staffan; Arnqvist, Anna; Lindén, Sara; Sjöström, Rolf; Gerhard, Markus; Semino-Mora, Cristina; Dubois, Andre; Unemo, Magnus; Danielsson, Dan; Teneberg, Susann; Lee, Woo-Kon; Berg, Douglas E.; Borén, Thomas

    2008-01-01

    Adherence of bacterial pathogens to host tissues contributes to colonization and virulence and typically involves specific interactions between bacterial proteins called adhesins and cognate oligosaccharide (glycan) or protein motifs in the host that are used as receptors. A given pathogen may have multiple adhesins, each specific for a different set of receptors and, potentially, with different roles in infection and disease. This chapter provides strategies for identifying and analyzing host glycan receptors and the bacterial adhesins that exploit them as receptors, with particular reference to adherence of the gastric pathogen Helicobacter pylori. PMID:17132512

  6. Case–control study of Epstein–Barr virus and Helicobacter pylori serology in Latin American patients with gastric disease

    PubMed Central

    Cárdenas-Mondragón, M G; Torres, J; Flores-Luna, L; Camorlinga-Ponce, M; Carreón-Talavera, R; Gomez-Delgado, A; Kasamatsu, E; Fuentes-Pananá, E M

    2015-01-01

    Background: Chronic tissue damage induced by Helicobacter pylori (HP)-driven inflammation is considered the main risk of gastric carcinoma (GC). Epstein–Barr virus (EBV) infection has also been associated with GC. In this study, we aim to address the role of EBV in inflammatory GC precursor lesions and its added risk to HP infection. Methods: Antibodies against EBV, HP and the bacterial virulence factor CagA were measured in sera from 525 Mexican and Paraguayan patients with gastric disease. Gastric samples were characterised according to the updated Sydney classification and associations were estimated between antibody responses and severity of both tissue damage and inflammation. Results: We found significant associations (odd ratios and trends) between EBV and HP copositivity and premalignant lesions and intestinal-type GC. The EBV and HP coinfection was also significantly associated with increased infiltration of immune cells. No association was found between EBV and the less inflammation-driven diffuse-type GC. Conclusions: Our study suggests that EBV co-participates with HP to induce severe inflammation, increasing the risk of progression to intestinal-type GC. PMID:25996206

  7. Effects of curcumin on Helicobacter pylori infection

    PubMed Central

    Vetvickova, Jana; Fernandez-Botran, Rafael

    2016-01-01

    Background Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. Methods Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. Results In all tests, one sample (Sabinsa) was consistently the most active. Conclusions All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity. PMID:28149841

  8. Thailand Consensus on Helicobacter pylori Treatment 2015.

    PubMed

    Mahachai, Varocha; Vilaichone, Ratha-Korn; Pittayanon, Rapat; Rojborwonwitaya, Jarin; Leelakusolvong, Somchai; Kositchaiwat, Chomsri; Mairiang, Pisaln; Praisontarangkul, Ong-Ard; Ovartlarnporn, Buncha; Sottisuporn, Jaksin; Pisespongsa, Pises; Maneerattanaporn, Monthira; Sony, Ravin; Sirinthornpunya, Siam; Chaiyamahapurk, Orawan; Wiwattanachang, Olarn; Sansak, Inchaya; Harnsomboon, Piyathida; Chitapanarux, Taned; Chuenrattanakul, Surapon

    2016-01-01

    Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes.

  9. Helicobacter Pylori Bacteremia: An Unusual Finding

    PubMed Central

    De Luca, Concetta; Mancin, Annalisa; Calabrò, Maria; Daleno, Cristina; Ferrario, Antonella; Renzulli, Raffaella; Scuderi, Cristina; Casari, Erminia

    2016-01-01

    We report a case of Helicobacter pylori transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gram-negative bacterium. This isolate was identified as H. pylori and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, H. pylori transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of Helicobacter pylori presence in blood.

  10. Epidemiology and Diagnosis of Helicobacter pylori infection.

    PubMed

    Mentis, Andreas; Lehours, Philippe; Mégraud, Francis

    2015-09-01

    During the period reviewed, prevalence studies were essentially performed in less economically advanced countries and a high prevalence was found. The traditional risk factors for Helicobacter pylori positivity were mostly found. Transmission studied by molecular typing showed a familial transmission. The eventual role of water transmission was explored in several studies with controversial results. Concerning diagnosis, most of the invasive and noninvasive methods used for the diagnosis of H. pylori infection are long standing with efficient performance. The most interesting recent improvements in H. pylori diagnosis include advances in endoscopy, developments in molecular methods, and the introduction of omics-based techniques. Interpretation of old or newer method should take into account the pretest probability and the prevalence of H. pylori in the population under investigation.

  11. Effectiveness of Citrus Fruits on Helicobacter pylori

    PubMed Central

    2017-01-01

    It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies.

  12. Characterization of Helicobacter pylori urease mutants.

    PubMed Central

    Segal, E D; Shon, J; Tompkins, L S

    1992-01-01

    The association between Helicobacter pylori, gastritis, and peptic ulcer is well established, and the association of infection with gastric cancer has been noted in several developing countries. However, the pathogenic mechanism(s) leading to disease states has not been elucidated. The H. pylori urease is thought to be a determinant of pathogenicity, since the enzyme is produced by all H. pylori clinical isolates. Evidence indicates that some H. pylori strains are more cytotoxic than others, with a correlation between the activity of the urease and the presence of a vacuolating cytotoxin having been made. However, the number of cytotoxins remains unknown at this time. The relationship between the urease and cytotoxicity has previously been examined with chemical inhibitors. To examine the role of the urease and its relationship to cytotoxicity, urease-deficient mutants were produced following ethyl methanesulfonate mutagenesis of H. pylori 87A300. Two mutants (the ure1 and ure5 mutants) which were entirely deficient in urease activity (Ure-) were selected. Characterization of the isolates at the protein level showed that the urease subunits lacked the ability to complex and form the active urease enzyme. The ure1 mutant was shown to be sensitive to the effects of low pH in vitro and exhibited no cytotoxicity to eucaryotic cells, whereas the parental strain (Ure+) produced a cytotoxic effect in the presence of urea. Interaction between the H. pylori Ure+ and Ure- strains and Caco-2 cells appeared to be similar in that both bacterial types elicited pedestal formation and actin condensation. These results indicate that the H. pylori urease may have many functions, among them (i) protecting H. pylori against the acidic environment of the stomach, (ii) acting as a cytotoxin, with human gastric cells especially susceptible to its activity, and (iii) disrupting cell tight junctions in such a manner that the cells remain viable but an ionic flow between the cells occurs

  13. Changing epidemiology of Helicobacter pylori in Japan.

    PubMed

    Inoue, Manami

    2017-03-01

    Helicobacter pylori (H. Pylori) is known as the most important cause of gastric cancer. The prevalence of H. pylori infection varies widely by geographic area, age, and socioeconomic status. In Japan, H. pylori infection has been highly correlated with the incidence rate of gastric cancer, and a reduction in H. pylori infection is therefore crucial for decreasing the incidence of gastric cancer, especially at the population level. Infection occurs during childhood, commonly before 5 years of age. In Japan, where gastric cancer has ranked as the most common cancer by incidence and mortality for the last several decades, the prevalence of H. pylori infection has dramatically declined by birth cohort effect, mainly due to improvements in the general hygiene environment in childhood. Older generations born before around 1950 show a high prevalence of around 80-90 %, decreasing with age to reach around 10 % or less in those born around the 1990s, and less than 2 % for children born after the year 2000. This change will have generational effects on gastric cancer prevention strategies, both primary and secondary. The risk-stratified approach to gastric cancer prevention should be considered in Japan and other countries which have similarly experienced rapid economic development.

  14. Helicobacter pylori and early gastric cancer.

    PubMed Central

    Craanen, M E; Blok, P; Dekker, W; Tytgat, G N

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered. PMID:7959189

  15. Evaluation of immobilized metal affinity chromatography kits for the purification of histidine-tagged recombinant CagA protein.

    PubMed

    Karakus, Cebrail; Uslu, Merve; Yazici, Duygu; Salih, Barik A

    2016-05-15

    Immobilized metal affinity chromatography (IMAC) technique is used for fast and reliable purification of histidine(His)-tagged recombinant proteins. The technique provides purification under native and denaturing conditions. The aim of this study is to evaluate three commercially available IMAC kits (Thermo Scientific, GE Healthcare and Qiagen) for the purification of a 6xHis-tagged recombinant CagA (cytotoxin-associated gene A) protein from IPTG-induced Escherichia coli BL21(DE3) culture. The kits were tested according to the manufacturer instructions and the protein was purified with only GE Healthcare and Qiagen kits under denaturing conditions. 1% (w/v) SDS was used as denaturing agent in PBS instead of extraction reagent of Thermo Scientific kit to lyse bacterial cells from 100ml culture. The 6xHis-tagged recombinant protein was purified by the three kits equally.

  16. Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

    PubMed Central

    Francesco, Vincenzo De; Ierardi, Enzo; Hassan, Cesare; Zullo, Angelo

    2009-01-01

    Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori (H pylori) infection should be remarked, especially regarding its potential oncologic risk. The inclusion of furazolidone in a treatment regimen for H pylori infection is, at least, controversial, and it does not appear to be safe. PMID:19370795

  17. Pathogenicity island cag, vacA and IS605 genotypes in Mexican strains of Helicobacter pylori associated with peptic ulcers

    PubMed Central

    2011-01-01

    Background Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. Two major virulence factors of H. pylori have been described: the pathogenicity island cag (cag PAI) and the vacuolating cytotoxin gene (vacA). Virtually all strains have a copy of vacA, but its genotype varies. The cag PAI is a region of 32 genes in which the insertion of IS605 elements in its middle region has been associated with partial or total deletions of it that have generated strains with varying virulence. Accordingly, the aim of this work was to determine the cag PAI integrity, vacA genotype and IS605 status in groups of isolates from Mexican patients with non-peptic ulcers (NPU), non-bleeding peptic ulcers (NBPU), and bleeding peptic ulcers (BPU). Methods The cag PAI integrity was performed by detection of eleven targeted genes along this locus using dot blot hybridization and PCR assays. The vacA allelic, cag PAI genotype 1 and IS605 status were determined by PCR analysis. Results Groups of 16-17 isolates (n = 50) from two patients with NPU, NBPU, and BPU, respectively, were studied. 90% (45/50) of the isolates harbored a complete cag PAI. Three BPU isolates lacked the cag PAI, and two of the NBPU had an incomplete cag PAI: the first isolate was negative for three of its genes, including deletion of the cagA gene, whereas the second did not have the cagM gene. Most of the strains (76%) had the vacA s1b/m1 genotype; meanwhile the IS605 was not present within the cag PAI of any strain but was detected elsewhere in the genome of 8% (4/50). Conclusion The patients had highly virulent strains since the most of them possessed a complete cag PAI and had a vacA s1b/m1 genotype. All the isolates presented the cag PAI without any IS605 insertion (genotype 1). Combined vacA genotypes showed that 1 NPU, 2 NBPU, and 1 BPU patients (66.6%) had a mixed infection; coexistence of H. pylori strains with different cag PAI status was observed in 1 NBPU and 2 BPU (50

  18. Optimizing the Growth of Stressed Helicobacter pylori

    PubMed Central

    Richards, Crystal L.; Buchholz, Brittany J.; Ford, Timothy E.; Broadaway, Susan C.; Pyle, Barry H.; Camper, Anne K.

    2010-01-01

    Helicobacter pylori is a Gram -negative bacterium that colonizes the human stomach and is responsible for causing gastric ulcers. H. pylori is known to become stressed and nonculturable after exposure to unfavorable conditions. In this study, we enhanced previously published resuscitation procedures, characterized conditions under which stressed H. pylori can be recovered, and formulated a selective and differential resuscitation medium. Results showed that a specialized broth supplemented with trace minerals and lysed human erythrocytes and serum is required for the recovery of nonculturable H. pylori. The type of stress was an important factor in the efficacy of resuscitation, with cells exposed to atmospheric oxygen more readily resuscitated than nutrient deprived cells. After resuscitation, culturable cells were recovered from previously nonculturable oxygen stressed cells (24 and 72 hours of exposure) and nonculturable nutrient deprived cells (24 hours of exposure). The length of time the cells were exposed to the stress was also an important factor in the recovery of stressed H. pylori. RNA levels were quantified and transcription of the cell division related gene, cdrA (HP0066), was assessed by qRT-PCR. The low levels of RNA detected in stressed cells, after resuscitation, support the idea that a small population of viable cells may be responsible for the colonies recovered on solid agar. The modification of the resuscitation broth into a selective and differential slant culture medium also allowed the recovery of stressed H. pylori. The methods presented here highlight the benefits and limitations of using human blood products for recovering nonculturable H. pylori. PMID:21129415

  19. Agglutination of Helicobacter pylori coccoids by lectins

    PubMed Central

    Khin, Mar Mar; Hua, Jie Song; Ng, Han Cong; Wadström, Torkel; Ho, Bow

    2000-01-01

    AIM: To study the agglutination pattern of Helicobacter pylori coccoid and spiral forms. METHODS: Assays of agglutination and agglutination inhibition were applied using fifteen commercial lectins. RESULTS: Strong agglutination was observed with mannose-specific Concanavalin A (Con A), fucose-specific Tetragonolobus purpureas (Lotus A) and N-acetyl glucosamine-specific Triticum vulgaris (WGA) lectins. Mannose and fucose specific lectins were reactive with all strains of H. pylori coccoids as compared to the spirals. Specific carbohydrates, glycoproteins and mucin were shown to inhibit H. pylori lectin-agglutination reactions. Pre-treatment of the bacterial cells with formalin and sulphuric acid did not alter the agglutination patterns with lectins. However, sodium periodate treatment of bacterial cells were shown to inhibit agglutination reaction with Con A, Lotus A and WGA lectins. On the contrary, enzymatic treatment of coccoids and spirals did not show marked inhibition of H. pylori lectin agglutination. Interes tingly, heating of H. pylori cells at 60 °C for 1 h was shown to augment the agglutination with all of the lectins tested. CONCLUSION: The considerable differences in lectin agglutination patterns seen among the two differentiated forms of H. pylori might be attributable to the structural changes during the events of morphological transformation, resulting in exposing or masking some of the sugar residues on the cell surface. Possibility of various sugar residues on the cell wall of the coccoids may allow them to bind to different carbohydrate receptors on gastric mucus and epithelial cells. The coccoids with adherence characteristics like the spirals could aid in the pathogenic process of Helicobacter infection. This may probably lead to different clinical outcome of H. pylori associated gastroduodenal disease. PMID:11819557

  20. Breath ammonia measurement in Helicobacter pylori infection.

    PubMed

    Kearney, David J; Hubbard, Todd; Putnam, David

    2002-11-01

    Our aim was to define the utility of breath ammonia measurement in assessing Helicobacter pylori infection. Volunteers breathed into a device containing three fiberoptic NH3 sensors at baseline and after ingesting 300 mg of urea. Breath ammonia levels were compared to the [14C]urea breath test. Thirteen subjects were tested. Before urea ingestion, H. pylori-positive subjects had significantly lower breath ammonia levels than negative subjects (mean +/- SD, 0.04 ppm +/- 0.09 vs 0.49 ppm +/- 0.24, P = 0.002) and had a significantly greater increases in breath ammonia after urea ingestion (range 198-1,494% vs 6-98%). One H. pylori-positive subject underwent treatment and breath ammonia levels shifted from the pattern seen in positive subjects to that seen in negative subjects. In conclusion, breath ammonia measurement for H. Pylori-positive and negative subjects showed distinct patterns. Breath ammonia measurement may be feasible as a diagnostic test for H. pylori.

  1. Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori.

    PubMed

    Li, Hong; Liao, Tingting; Debowski, Aleksandra W; Tang, Hong; Nilsson, Hans-Olof; Stubbs, Keith A; Marshall, Barry J; Benghezal, Mohammed

    2016-12-01

    This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram-negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O-antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa-saccharide (Kdo-LD-Hep-LD-Hep-DD-Hep-Gal-Glc), the outer core composed of a conserved trisaccharide (-GlcNAc-Fuc-DD-Hep-) linked to the third heptose of the inner core, the glucan, the heptan and a variable O-antigen, generally consisting of a poly-LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O-antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium.

  2. Immune evasion strategies used by Helicobacter pylori.

    PubMed

    Lina, Taslima T; Alzahrani, Shatha; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E

    2014-09-28

    Helicobacter pylori (H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival.

  3. N-acetylcysteine, a novel treatment for Helicobacter pylori infection.

    PubMed

    Huynh, Hien Quoc; Couper, Richard T L; Tran, Cuong D; Moore, Lynette; Kelso, Richard; Butler, Ross N

    2004-01-01

    N-Acetylcysteine (NAC), being both a mucolytic agent and a thiol-containing antioxidant, may affect the establishment and maintenance of H. pylori infection within the gastric mucus layer and mucosa. Agar and broth dilution susceptibility tests determined the MIC of H. pylori strain SSI to NAC. H. pylori load in SSI strain-infected C57BL mice was determined as colony forming units per gram of gastric tissue. Gastritis assessment was scored and gastric surface hydrophobicity was determined by contact angle measurement. MICs of NAC were 5 to 10 and 10 to 15 mg/ml using the agar dilution and broth dilution methods, respectively. NAC (120 mg per day for 14 days) reduced the H. pylori load in mice by almost 1 log compared with sham treatment. Pretreatment with NAC (40 mg/day) also significantly reduced the H. pylori load but did not prevent H. pylori colonization. Both H. pylori infection and NAC reduced the surface hydrophobicity of murine gastric mucosa. No significant differences were observed in the gastritis scores of H. felis- or H. pylori-infected mice receiving either NAC or sham treatments. This study demonstrates that NAC inhibits the growth of H. pylori in both agar and broth susceptibility tests and in H. pylori-infected mice. NAC did not alter the severity of H. pylori- or H. felis-induced gastritis.

  4. A Case of Small Bowel Ulcer Associated with Helicobacter pylori

    PubMed Central

    Kim, Eun Young; Kim, Ji Hyun; Woo, Saet Byul; Lee, Jeong Won; Lee, Kon Hee; Shin, Su Rin

    2012-01-01

    The etiology of peptic ulcer disease in children may be primary, associated with Helicobacter pylori infection, or secondary, relied on underlying disease. Ulcerative lesions by H. pylori are mainly distributed in the duodenal bulb and they are rare below the ampulla of Vater because H. pylori growth is inhibited by bile juice. In this reason, there are only some restrictive reports presented small bowel ulcer associated H. pylori. We found multiple small bowel ulcerative lesions associated with H. pylori in an 11-year-old girl without any systemic disease while performing esophagogastroenteroscopy to the level of the proximal jejunum for differentiating bezoar. The abdominal pain improved after the patient was administered H. pylori eradication therapy. Because a small bowel ulcer associated with H. pylori has rarely been reported, we report it here with literature review. PMID:24010097

  5. Prevalence of Helicobacter pylori in United States Navy submarine crews.

    PubMed

    Jackman, R P; Schlichting, C; Carr, W; Dubois, A

    2006-06-01

    Helicobacter pylori prevalence is elevated in German submarine crews and in United States Navy (USN) surface fleet personnel, but H. pylori prevalence in USN submariners was unknown. The goal of the study was to determine the prevalence of H. pylori in the crews of USN nuclear submarines compared to other military personnel and to the general US population. The presence of H. pylori IgG antibodies was determined in serum samples using a commercial ELISA. Only 47 out of 451 submariners (9.4%) were H. pylori positive, which is similar to that of the US general population with a similar level of education. In contrast, H. pylori prevalence is significantly higher in US Army recruits (26%), USN surface fleet personnel (25%), and German diesel submariners (38%). These data demonstrate that submarine service (and by inference activity requiring isolation and close contact, per se) is not a risk factor for H. pylori infection.

  6. A CCD-based reader combined with CdS quantum dot-labeled lateral flow strips for ultrasensitive quantitative detection of CagA

    NASA Astrophysics Data System (ADS)

    Gui, Chen; Wang, Kan; Li, Chao; Dai, Xuan; Cui, Daxiang

    2014-02-01

    Immunochromatographic assays are widely used to detect many analytes. CagA is proved to be associated closely with initiation of gastric carcinoma. Here, we reported that a charge-coupled device (CCD)-based test strip reader combined with CdS quantum dot-labeled lateral flow strips for quantitative detection of CagA was developed, which used 365-nm ultraviolet LED as the excitation light source, and captured the test strip images through an acquisition module. Then, the captured image was transferred to the computer and was processed by a software system. A revised weighted threshold histogram equalization (WTHE) image processing algorithm was applied to analyze the result. CdS quantum dot-labeled lateral flow strips for detection of CagA were prepared. One hundred sera samples from clinical patients with gastric cancer and healthy people were prepared for detection, which demonstrated that the device could realize rapid, stable, and point-of-care detection, with a sensitivity of 20 pg/mL.

  7. Theoretical study of silver-ion-mediated base pairs: the case of C-Ag-C and C-Ag-A systems.

    PubMed

    Fortino, Mariagrazia; Marino, Tiziana; Russo, Nino

    2015-05-28

    Silver-mediated base pairs applied to DNA represent a new biomacromolecular nanomaterial useful for generating nanodevices as ion sensors. Reported herein is a full quantum chemical study devoted to give further knowledge on the electronic and energetic properties of C-Ag-C and mixed C-Ag-A mismatched base pairs. The B3LYP functional in conjunction with the dispersion effects (D3) has been applied. Single-point calculations have been also performed by using the M06-L functional. The investigation of their behavior has been extended to the duplex DNA modeled by the (dC-Ag-dC)2 and (dC-Ag-dA)2 more complex systems. The solvent effect has been taken into account by the conductor-like screening model, COSMO. In the case of mixed C-Ag-A and (dC-Ag-dA)2 systems, both the Watson-Crick and Hoogsteen arrangements have been taken into account. Results show that for (dC-Ag-dA)2 systems, the binding energies are almost double that of the corresponding values of C-Ag-A ones.

  8. Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

    PubMed

    Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C

    2014-05-01

    Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies.

  9. Heat shock protein produced by Helicobacter pylori.

    PubMed

    Yokota, K; Hirai, Y; Haque, M; Hayashi, S; Isogai, H; Sugiyama, T; Nagamachi, E; Tsukada, Y; Fujii, N; Oguma, K

    1994-01-01

    The cells of Helicobacter pylori were suspended in the medium containing 35S-methionine. After a heat shock of the cells at 42 C for 5, 10, and 30 min, the production of proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Out of many proteins produced by the cells, only 66 kDa protein production was dramatically increased by heat treatment. The N-terminal amino acid sequence of 66 kDa protein was quite similar to that of 62 kDa and 54 kDa proteins previously suggested as heat shock protein (HSP) of H. pylori based on the reaction with polyclonal and monoclonal antibodies against HSP 60 family proteins produced by other bacteria. Therefore, it was concluded that H. pylori produces the 66 kDa protein as its major heat shock protein which belongs to HSP 60 family.

  10. Helicobacter pylori Detection and Antimicrobial Susceptibility Testing

    PubMed Central

    Mégraud, Francis; Lehours, Philippe

    2007-01-01

    The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed. PMID:17428887

  11. Impact of Helicobacter Pylori on Mucus Rheology

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Keates, Sarah; Kelly, Ciaran; Turner, Bradley; Bansil, Rama; Erramilli, Shyamsunder

    2006-03-01

    It is well known that the viscoelastic properties of gastric mucin are crucial to the protection of the lining of the stomach against its own acidic secretions and other agents. Helicobacter Pylori, a rod shaped, gram-negative bacteria that dwells in the mucus layer of approximately 50% of the world's population is a class I carcinogen and is associated with gastric ulcers and severe gastritis. The structural damage to the mucus layer caused by H. Pylori is an important aspect of infection with this bacteria. We are examining the impact of H. Pylori on mucin and mucus rheology quantitatively using a combination of dynamic light scattering and multiple particle tracking experiments. Video microscopy data will also be presented on the motility of this bacteria in mucin at different pH and in other viscoelastic gels.

  12. Rate and extent of Helicobacter pylori phagocytosis.

    PubMed

    Allen, Lee-Ann H

    2008-01-01

    Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric epithelium and plays a causative role in the development of peptic ulcers and gastric cancer. Phagocytosis is an element of innate defense used by macrophages and neutrophils to engulf microorganisms. We and others have shown that strains of H. pylori that contain the cag pathogenicity island actively retard their entry into phagocytes. Consequently, there is a lag of several minutes between bacterial binding and the onset of engulfment, and relative to other particles and microbes, the rate of internalization is slow. Herein, we describe in detail the use of synchronized phagocytosis and indirect immunofluorescence microscopy to quantify the rate and extent of H. pylori phagocytosis. This method is appropriate for primary phagocytes as well as transformed cell lines. More importantly, the effects of opsonins, virulence factors, and other agents on infection can be measured independent of bacterial viability or intracellular locale.

  13. Recent "omics" advances in Helicobacter pylori.

    PubMed

    Berthenet, Elvire; Sheppard, Sam; Vale, Filipa F

    2016-09-01

    The development of high-throughput whole genome sequencing (WGS) technologies is changing the face of microbiology, facilitating the comparison of large numbers of genomes from different lineages of a same organism. Our aim was to review the main advances on Helicobacter pylori "omics" and to understand how this is improving our knowledge of the biology, diversity and pathogenesis of H. pylori. Since the first H. pylori isolate was sequenced in 1997, 510 genomes have been deposited in the NCBI archive, providing a basis for improved understanding of the epidemiology and evolution of this important pathogen. This review focuses on works published between April 2015 and March 2016. Helicobacter "omics" is already making an impact and is a growing research field. Ultimately these advances will be translated into a routine clinical laboratory setting in order to improve public health.

  14. Helicobacter pylori vaccine: from past to future.

    PubMed

    Agarwal, Kanishtha; Agarwal, Shvetank

    2008-02-01

    Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.

  15. Detection of Helicobacter pylori in Oral Lesions

    PubMed Central

    Irani, Soussan; Monsef Esfahani, Alireza; Bidari Zerehpoush, Farahnaz

    2013-01-01

    Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC) and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000). In addition, there was a statistically significant difference between the lesions examined (P=0.042). Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000), inside the blood vessels (P=0.003), inside the salivary gland duct (P=0.036), and muscle layer (P=0.122). Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested. PMID:24578822

  16. [Celiac disease associated with Helicobacter pylori infection].

    PubMed

    Cârdei, E; Moraru, D; Trandafir, Laura; Bozomitu, Laura; Mihăilă, Doina

    2003-01-01

    Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune enteropathy caused by the ingestion of gluten-containing grains in susceptible subjects. The authors present a 3 years and 5 months old girl diagnosed with celiac disease at 1 year and 5 months old. Initially, the evolution after gluten-free diet was favorable. After 2 years the child presented abdominal pain and anorexia. The IgA antigliadin antibodies had normal values. The gastric biopsy found Helicobacter pylori gastritis. After treatment for Helicobacter pylori eradication the symptoms disappeared.

  17. Integrin Engagement by the Helical RGD Motif of the Helicobacter pylori CagL Protein Is Regulated by pH-induced Displacement of a Neighboring Helix*

    PubMed Central

    Bonsor, Daniel A.; Pham, Kieu T.; Beadenkopf, Robert; Diederichs, Kay; Haas, Rainer; Beckett, Dorothy; Fischer, Wolfgang; Sundberg, Eric J.

    2015-01-01

    Arginine-aspartate-glycine (RGD) motifs are recognized by integrins to bridge cells to one another and the extracellular matrix. RGD motifs typically reside in exposed loop conformations. X-ray crystal structures of the Helicobacter pylori protein CagL revealed that RGD motifs can also exist in helical regions of proteins. Interactions between CagL and host gastric epithelial cell via integrins are required for the translocation of the bacterial oncoprotein CagA. Here, we have investigated the molecular basis of the CagL-host cell interactions using structural, biophysical, and functional analyses. We solved an x-ray crystal structure of CagL that revealed conformational changes induced by low pH not present in previous structures. Using analytical ultracentrifugation, we found that pH-induced conformational changes in CagL occur in solution and not just in the crystalline environment. By designing numerous CagL mutants based on all available crystal structures, we probed the functional roles of CagL conformational changes on cell surface integrin engagement. Together, our data indicate that the helical RGD motif in CagL is buried by a neighboring helix at low pH to inhibit CagL binding to integrin, whereas at neutral pH the neighboring helix is displaced to allow integrin access to the CagL RGD motif. This novel molecular mechanism of regulating integrin-RGD motif interactions by changes in the chemical environment provides new insight to H. pylori-mediated oncogenesis. PMID:25837254

  18. Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix.

    PubMed

    Bonsor, Daniel A; Pham, Kieu T; Beadenkopf, Robert; Diederichs, Kay; Haas, Rainer; Beckett, Dorothy; Fischer, Wolfgang; Sundberg, Eric J

    2015-05-15

    Arginine-aspartate-glycine (RGD) motifs are recognized by integrins to bridge cells to one another and the extracellular matrix. RGD motifs typically reside in exposed loop conformations. X-ray crystal structures of the Helicobacter pylori protein CagL revealed that RGD motifs can also exist in helical regions of proteins. Interactions between CagL and host gastric epithelial cell via integrins are required for the translocation of the bacterial oncoprotein CagA. Here, we have investigated the molecular basis of the CagL-host cell interactions using structural, biophysical, and functional analyses. We solved an x-ray crystal structure of CagL that revealed conformational changes induced by low pH not present in previous structures. Using analytical ultracentrifugation, we found that pH-induced conformational changes in CagL occur in solution and not just in the crystalline environment. By designing numerous CagL mutants based on all available crystal structures, we probed the functional roles of CagL conformational changes on cell surface integrin engagement. Together, our data indicate that the helical RGD motif in CagL is buried by a neighboring helix at low pH to inhibit CagL binding to integrin, whereas at neutral pH the neighboring helix is displaced to allow integrin access to the CagL RGD motif. This novel molecular mechanism of regulating integrin-RGD motif interactions by changes in the chemical environment provides new insight to H. pylori-mediated oncogenesis.

  19. Antimicrobial Nanotherapeutics Against Helicobacter pylori Infection

    NASA Astrophysics Data System (ADS)

    Thamphiwatana, Soracha

    Helicobacter pylori (H. pylori) infection with its vast prevalence is responsible for various gastric diseases including gastritis, peptic ulcers, and gastric malignancy. While effective, current treatment regimens are challenged by a fast-declining eradication rate due to the increasing emergence of H. pylori strains resistant to existing antibiotics. Therefore, there is an urgent need to develop novel antibacterial strategies against H. pylori. The first area of this research, we developed a liposomal nanoformulation of linolenic acid (LipoLLA) and evaluated its bactericidal activity against resistant strains of H. pylori. We found that LipoLLA was effective in killing both spiral and dormant forms of the bacteria via disrupting bacterial membranes. LipoLLA eradicated all strains of the bacteria regardless of their antibiotic resistance status. Furthermore, the bacteria did not develop drug resistance toward LipoLLA. Our findings suggest that LipoLLA is a promising antibacterial nanotherapeutic to treat antibiotic-resistant H. pylori infection. The next step, we investigated the in vivo therapeutic potential of LipoLLA for the treatment of H. pylori infection. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha, which were otherwise elevated due to the H. pylori infection. Finally, toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this work indicate that LipoLLA is a promising, new, effective, and safe therapeutic agent for the treatment of H. pylori infection. The second area is stimuli-responsive liposomes development. By adsorbing small chitosan-modified gold nanoparticles (AuChi) onto the outer surface of liposomes, we show that at gastric pH the liposomes have

  20. Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection

    PubMed Central

    Yang, Jyh-Chin; Yang, Hung-Chih; Shun, Chia-Tung; Wang, Teh-Hong; Chien, Chiang-Ting; Kao, John Y.

    2013-01-01

    The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs), sialic acid (SA), or combination of CA and SA (CASA) on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells) and in vivo (BALB/c mice). Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection. PMID:23653660

  1. Helicobacter pylori infection - recent developments in diagnosis

    PubMed Central

    Lopes, Ana Isabel; Vale, Filipa F; Oleastro, Mónica

    2014-01-01

    Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance. PMID:25071324

  2. [Gastrointestinal giardiasis associated with Helicobacter pylori].

    PubMed

    Isaeva, G Sh; Efimova, N G

    2010-01-01

    The study involved 160 patients with chronic cholecystitis associated with chronic gastroduodenitis. Obtaining biopsy specimens of gastric mucosa and bile samples allowed to compare the microbial picture and the morphological structure of gastric mucosa in the same patient, to identify patterns of colonization of the stomach, 12 duodenal ulcer and gall bladder various microorganisms. At cytological examination was detected in the gall bladder G. lamblia in 47.5 +/- 3.95% of cases in the stomach--in 29.09 +/- 6.12% of cases. The frequency of H. pylori detection in biopsy of gastric mucosa amounted to 98.18 +/- 1.8% of cases, in 12-duodenum--93.75 +/- 1.9%, in the gall bladder--to 54.38 +/- 3.94%, in the bile duct--in 54.38 +/- 3.94%. It was found strict association between the detection of H. pylori and G. lamblia in the stomach--100% of H. pylori-infection combined with giardiasis. Morphological changes of gastric mucosa in the form of lymphoid infiltration detected mainly in the mixed-infection H. pylori and G. lamblia.

  3. Helicobacter pylori infection - recent developments in diagnosis.

    PubMed

    Lopes, Ana Isabel; Vale, Filipa F; Oleastro, Mónica

    2014-07-28

    Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance.

  4. Bacteriology and taxonomy of Helicobacter pylori.

    PubMed

    Windsor, H M; O'Rourke, J

    2000-09-01

    As the scientific community approaches the twentieth anniversary of the first isolation of H. pylori, it appears that despite the wealth of articles published in journals throughout the world every month, there are still many unanswered questions about the microbiology of this bacterium and others in the genus Helicobacter.

  5. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    PubMed

    Zhu, Xinyan; Liu, Fei

    2017-03-10

    Over 80% population with Helicobacter pylori (H. pylori) infection is asymptomatic. H. pylori was considered as a primary reason for various natural gastric physiopathology. Increased antibiotic resistance and less medication compliance lead to the failure of antibiotic eradication therapy. Probiotics have been applied as a supplementary treatment in H. pylori eradication therapy in recent years. They have direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials. Because of the improvement in eradication rates and therapy-related side effects, probiotics have been considered as the useful supplementation to current eradication therapy although the treatment outcomes were controversial due to the heterogeneity of probiotics in species, strains, doses and therapeutic duration. Despite the positive role of probiotics, several factors need to be further considered during the application of probiotics. At last, the adverse effects of probiotics are notable. Further investigation into the safety of adjuvant probiotics to present H. pylori eradication therapy is still needed.

  6. Extraintestinal manifestations of Helicobacter pylori: A concise review

    PubMed Central

    Wong, Frank; Rayner-Hartley, Erin; Byrne, Michael F

    2014-01-01

    Helicobacter pylori (H. pylori) infection has been clearly linked to peptic ulcer disease and some gastrointestinal malignancies. Increasing evidence demonstrates possible associations to disease states in other organ systems, known as the extraintestinal manifestations of H. pylori. Different conditions associated with H. pylori infection include those from hematologic, cardiopulmonary, metabolic, neurologic, and dermatologic systems. The aim of this article is to provide a concise review of the evidence that supports or refutes the associations of H. pylori and its proposed extraintestinal manifestations. Based on data from the literature, PUD, mucosal associated lymphoid tumors lymphoma, and gastric adenocarcinoma has well-established links. Current evidence most supports extraintestinal manifestations with H. pylori in immune thrombocytopenic purpura, iron deficiency anemia, urticaria, Parkinson’s, migraines and rosacea; however, there is still plausible link with other diseases that requires further research. PMID:25232230

  7. Helicobacter pylori infection: New pathogenetic and clinical aspects

    PubMed Central

    Hagymási, Krisztina; Tulassay, Zsolt

    2014-01-01

    Helicobacter pylori (H. pylori) infects more than half of the world’s human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial. PMID:24914360

  8. Immunobiological activities of Helicobacter pylori porins.

    PubMed Central

    Tufano, M A; Rossano, F; Catalanotti, P; Liguori, G; Capasso, C; Ceccarelli, M T; Marinelli, P

    1994-01-01

    Studies were carried out on some biological activities of Helicobacter pylori porins in vitro. We extracted and purified a porin with an apparent molecular mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori porins showed a decrease of chemotaxis, of adherence to nylon wool, and of chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as chemotaxinogens in place of zymosan, the porins induced polymorphonuclear leukocyte migration. Human monocytes and lymphocytes cultivated in the presence of H. pylori porins released cytokines. Release of the various cytokines studied was obtained with differentiated kinetics and at various porin concentrations. Starting only 3 h after culture, tumor necrosis factor alpha is released quickly, reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells. Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release gamma interferon after 18 h of culture at higher concentrations of porins (20 micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while both IL-3 and IL-4 are released after 18 h of culture at different porin concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results lead us to think that during H. pylori infection, surface components, porins in particular, are able to induce a series of chain reactions ranging from the inflammatory to the immunological responses. Images PMID:8132346

  9. Association between thyroid autoimmunity and Helicobacter pylori infection

    PubMed Central

    Choi, Yun Mi; Kim, Tae Yong; Kim, Eui Young; Jang, Eun Kyung; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2017-01-01

    Background/Aims There have been controversial reports linking Helicobacter pylori infection to autoimmune thyroid disease (AITD). However, data regarding the relationship are limited for Asian populations, which have an extremely high prevalence of H. pylori infection. We performed this study to investigate the association between H. pylori infection and AITD in Koreans. Methods This study involved adults aged 30 to 70 years who had visited a health promotion center. A total of 5,502 subjects were analysed. Thyroid status was assessed by free thyroxine, thyroid stimulating hormone, and anti-thyroid peroxidase antibody (TPO-Ab). Immunoglobulin G (IgG) antibodies to H. pylori were measured as an indication of H. pylori infection. We compared the prevalence of TPO-Ab in subjects with and without H. pylori infection. Results H. pylori IgG antibodies were found in 2,875 subjects (52.3%), and TPO-Ab were found in 430 (7.8%). Individuals positive for H. pylori Ab were older than those negative for H. pylori Ab (p < 0.01). The proportion of females was significantly higher in the TPO-Ab positive group (41.0% vs. 64.2%, p < 0.01). Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (8.6% vs. 7.00%, p = 0.03), and this association was significant after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04). Conclusions In our study, prevalence of TPO-Ab positivity is more frequent in subjects with H. pylori infection. Our findings suggest H. pylori infection may play a role in the development of autoimmune thyroiditis. PMID:28092700

  10. [On the rating of Helicobacter pylori in drinking water].

    PubMed

    Fedichkina, T P; Solenova, L G; Zykova, I E

    2014-01-01

    There are considered the issues related to the possibility to rate of Helicobacter pylori (H. pylori) content in drinking water. There is described the mechanism of of biofilm formation. The description refers to the biofilm formation mechanism in water supply systems and the existence of H. pylori in those systems. The objective premises of the definition of H. pylori as a potential limiting factor for assessing the quality of drinking water have been validated as follows: H. pylori is an etiologic factor associated to the development of chronic antral gastritis, gastric ulcer and duodenal ulcer, and gastric cancer either, in the Russian population the rate of infection with H. pylori falls within range of 56 - 90%, water supply pathway now can be considered as a source of infection of the population with H. pylori, the existence of WHO regulatory documents considering H. pylori as a candidate for standardization of the quality of the drinking water quite common occurrence of biocorrosion, the reduction of sanitary water network reliability, that creates the possibility of concentrating H. pylori in some areas of the water system and its delivery to the consumer of drinking water, and causes the necessity of the prevention of H. pylori-associated gastric pathology of the population. A comprehensive and harmonized approach to H. pylori is required to consider it as a candidate to its rating in drinking water. Bearing in mind the large economic losses due to, on the one hand, the prevalence of disease caused by H. pylori, and, on the other hand, the biocorrosion of water supply system, the problem is both relevant in terms of communal hygiene and economy.

  11. Helicobacter pylori infection in Canada's arctic: searching for the solutions.

    PubMed

    Cheung, Justin; Goodman, Karen; Munday, Rachel; Heavner, Karen; Huntington, Janis; Morse, John; Veldhuyzen van Zanten, Sander; Fedorak, Richard N; Corriveau, Andre; Bailey, Robert J

    2008-11-01

    The Canadian North Helicobacter pylori (CANHelp) working group is a team composed of investigators, health officials and community leaders from Alberta and the Northwest Territories. The group's initial goals are to investigate the impact of H pylori infection on Canada's Arctic communities; subsequent goals include identifying treatment strategies that are effective in this region and developing recommendations for health policy aimed at management of H pylori infection. The team's investigations have begun with the Aklavik H pylori Project in the Aboriginal community of Aklavik, Northwest Territories.

  12. Helicobacter pylori infection following partial gastrectomy for gastric cancer

    PubMed Central

    Park, Sanghoon; Chun, Hoon Jai

    2014-01-01

    Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer. The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori) infection is also a well-known characteristic of gastric carcinogenesis. H. pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis; however, the H. pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis. For instance, H. pylori infection of the gastric stump produced controversial results in several recent studies. The prevalence of H. pylori infection in the gastric stump has varied among recent reports. Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ. Bile refluxate also has a significant influence on the colonization of the stomach stump, with several studies reporting mixed results as well. In contrast, the elimination of H. pylori from the gastric stump has shown a dramatic impact on eradication rate. H. pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers. To overcome the current discrepancies in the literature regarding the role of H. pylori in the gastric stump, further research is required. PMID:24659869

  13. Chronic Gastritis and its Association with H. Pylori Infection.

    PubMed

    Fatema, J; Khan, A H; Uddin, M J; Rahman, M H; Saha, M; Safwath, S A; Alam, M J; Mamun, M A

    2015-10-01

    This cross sectional study was designed to see association of chronic gastritis including its type with H. pylori infection. Consecutive patients undergoing endoscopic examination having histopathological evidence of chronic gastritis were enrolled in the study and was done in Sylhet MAG Osmani Medical College from July 2011 to June 2012. Biopsies were taken from antrum, body and fundus in all patients. Histopathological examinations were done using H-E stain and for detection of H. pylori, rapid urease test, anti-H.pylori antibody test and histopathological test with modified Giemsa stain were done. Patients having results positive in at least two methods were considered infected by H. pylori. Total 80 dyspeptic patients having chronic gastritis were evaluated. Out of them 67(83.8%) had H. pylori infection and 13(16.2%) were H. pylori negative. Among all patients 57(71.2%) had pangastritis and 23(28.8%) had antral gastritis with female and male predominance respectively. H. pylori infection was present in 49(86.0%) cases of pangastritis and 18(78.3%) cases of antral gastritis. H. pylori infection was a little higher among males (34, 50.7%) females (33, 49.3%). H. pylori infection is the predominant cause of chronic gastritis and pangastritis is the major type.

  14. Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis.

    PubMed

    Shao, Yun; Sun, Kun; Xu, Wei; Li, Xiao-Lin; Shen, Hong; Sun, Wei-Hao

    2014-09-28

    Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.

  15. Inflammation, DNA Damage, Helicobacter pylori and Gastric Tumorigenesis

    PubMed Central

    Kalisperati, Polyxeni; Spanou, Evangelia; Pateras, Ioannis S.; Korkolopoulou, Penelope; Varvarigou, Anastasia; Karavokyros, Ioannis; Gorgoulis, Vassilis G.; Vlachoyiannopoulos, Panayiotis G.; Sougioultzis, Stavros

    2017-01-01

    Helicobacter pylori (H. pylori) is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably double strand breaks. The epithelial host cell responds by activation of DNA damage repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of H. pylori induced carcinogenesis. Here, we review the data on the molecular pathways involved in DNA damage and DDR activation during H. pylori infection. PMID:28289428

  16. Growth in children with Helicobacter pylori infection and dyspepsia

    PubMed Central

    Sood, M; Joshi, S; Akobeng, A; Mitchell, J; Thomas, A

    2005-01-01

    Aims: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. Methods: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients' postcodes. Results: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. Conclusion: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection. PMID:15956048

  17. Management of Helicobacter pylori infection after gastric surgery.

    PubMed

    Lin, Yang-Sheng; Chen, Ming-Jen; Shih, Shou-Chuan; Bair, Ming-Joug; Fang, Ching-Ju; Wang, Horng-Yuan

    2014-05-14

    The Maastricht IV/Florence Consensus Report and the Second Asia-Pacific Consensus Guidelines strongly recommend eradication of Helicobacter pylori (H. pylori) in patients with previous gastric neoplasia who have undergone gastric surgery. However, the guidelines do not mention optimal timing, eradication regimens, diagnostic tools, and follow-up strategies for patients undergoing gastrectomy and do not indicate if eradication of H. pylori reduces the risk of marginal ulcer or stump cancer in the residual stomach after gastrectomy. The purpose of this review is to provide an update which may help physicians to properly manage H. pylori infection in patients who have undergone gastric surgery. This review focuses on (1) the microenvironment change in the stomach after gastrectomy; (2) the phenomenon of spontaneous clearance of H. pylori after gastrectomy; (3) the effects of H. pylori on gastric atrophy and intestinal metaplasia after gastrectomy; (4) incidence and clinical features of ulcers developing after gastrectomy; (5) does eradication of H. pylori reduce the risk of gastric stump cancer in the residual stomach? (6) does eradication of H. pylori reduce the risk of secondary metachronous gastric cancer in the residual stomach? and (7) optimal timing and regimens for H. pylori eradication, diagnostic tools and follow-up strategies for patients undergoing gastrectomy.

  18. Helicobacter pylori infection and expression of DNA mismatch repair proteins

    PubMed Central

    Mirzaee, Vahid; Molaei, Mahsa; Shalmani, Hamid Mohaghegh; Zali, Mohammad Reza

    2008-01-01

    AIM: To determine the expression of DNA (MMR) proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori (H pylori)-infected gastritis. METHODS: Fifty H pylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination (Giemsa stain) and for immunohistochemical staining of hMLH1 and hMSH2. RESULTS: The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 ± 7.32% in H pylori-negative patients, while it was 73.34 ± 10.10% in H pylori-positive patients (P < 0.0001). No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining (81.16 ± 8.32% in H pylori-negative versus 78.24 ± 8.71% in H pylori-positive patients; P = 0.09). CONCLUSION: This study indicates that H pylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system. PMID:19034977

  19. Prevalence of Helicobacter pylori in Gastric Hyperplastic Polyps.

    PubMed

    Horvath, Bela; Pai, Rish K

    2016-12-01

    Hyperplastic polyps of the stomach are routinely encountered during upper endoscopy and often arise in the setting of abnormal surrounding mucosa, particularly Helicobacter pylori, autoimmune gastritis, and reactive gastropathy. Not infrequently gastroenterologists fail to biopsy the surrounding mucosa, thus determining the underlying etiology of the gastric hyperplastic polyp can be difficult. Recently, the Rodger C. Haggitt Gastrointestinal Pathology Society published guidelines on the use of special stains. The society guidelines indicate that H pylori are not usually present in hyperplastic polyps and special stains in this setting may have limited utility. We analyzed the histologic features of 32 gastric hyperplastic polyps in which the nonpolypoid mucosa demonstrated H pylori gastritis. A consecutive series of 50 hyperplastic polyps in which no surrounding mucosa was sampled was also analyzed. When H pylori are identified in biopsies of the nonpolypoid mucosa, it is also commonly present within the polyp tissue (22/32, 69%). The majority of H pylori organisms were identified on routine hematoxylin and eosin stain (16/22, 72%). In contrast, H pylori were only seen in 2/50 consecutive hyperplastic polyps in which the surrounding mucosa was not sampled. Compared with the hyperplastic polyps that lack the organisms, H pylori associated hyperplastic polyps more commonly had dense lymphoplasmacytic inflammation (P = .0001) and neutrophils within gastric epithelium (P = .036). Polyp location, number, size, and presence of intestinal metaplasia was not associated with H pylori These results provide empirical data to guide evaluation of hyperplastic polyps for H pylori.

  20. Inflammation, immunity, and vaccines for Helicobacter pylori infection.

    PubMed

    Velin, Dominique; Straubinger, Kathrin; Gerhard, Markus

    2016-09-01

    The tight control of the innate and adaptive immune responses in the stomach mucosa during chronic Helicobacter pylori infection is of prime importance for the bacteria to persist and for the host to prevent inflammation-driven diseases. This review summarizes recent data on the roles of innate and adaptive immune responses during H. pylori/host interactions. In addition, the latest preclinical developments of H. pylori vaccines are discussed with a special focus on the clinical trial reported by Zeng et al., who provided evidence that oral vaccination significantly reduces the acquisition of natural H. pylori infection in children.

  1. Helicobacter pylori infection in Canadian and related Arctic Aboriginal populations.

    PubMed

    Goodman, K J; Jacobson, K; Veldhuyzen van Zanten, S

    2008-03-01

    In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities.

  2. Host pathogen interactions in Helicobacter pylori related gastric cancer.

    PubMed

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-03-07

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

  3. Helicobacter pylori infection and chronic gastritis in gastric cancer.

    PubMed Central

    Sipponen, P.; Kosunen, T. U.; Valle, J.; Riihelä, M.; Seppälä, K.

    1992-01-01

    AIMS: To investigate the prevalence of Helicobacter pylori associated chronic gastritis in patients with gastric cancer. METHODS: Serum IgG antibodies for H pylori were determined in 54 consecutive patients with gastric carcinoma. The prevalence of H pylori in gastric mucosa was also examined histologically (modified Giemsa) in 32 patients from whom adequate biopsy specimens of the antrum and corpus were available. Thirty five patients with gastrointestinal tumours outside the stomach and 48 with non-gastrointestinal malignancies served as controls. RESULTS: Of the 54 patients, 38 (70%) had H pylori antibodies (IgG) in their serum (three additional patients had H pylori antibodies IgA, class specific but not IgG specific). This prevalence was significantly higher (p less than 0.05) than that (49%) in the 35 controls. No differences in prevalence of H pylori antibodies were found between gastric cancer cases of intestinal (IGCA) or diffuse (DGCA) type, both these types showing H pylori antibodies (IgG) in 71% of the patients. In the subgroup of 32 subjects, five patients had normal gastric mucosa and four showed corpus limited atrophy ("pernicious anaemia type" atrophy of type A). All of these nine patients had no evidence of current or previous H pylori infection in serum (no IgG antibodies) or in tissue sections (negative Giemsa staining). The remaining 23 patients had antral or pangastritis, and all had evidence of current or previous H pylori infection. CONCLUSIONS: H pylori associated chronic gastritis was the associated disease in 75% of the patients with gastric cancer occurring equally often in both IGCA and DGCA groups. About 25% of cases seem to have a normal stomach or severe corpus limited atrophy, neither of which showed evidence of concomitant H pylori infection. PMID:1577969

  4. Helicobacter pylori-Negative Gastritis: Prevalence and Risk Factors

    PubMed Central

    Nordenstedt, Helena; Graham, David Y.; Kramer, Jennifer R.; Rugge, Massimo; Verstovsek, Gordana; Fitzgerald, Stephanie; Alsarraj, Abeer; Shaib, Yasser; Velez, Maria E.; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B.

    2014-01-01

    OBJECTIVES Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. METHODS Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. RESULTS Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P = 0.06). CONCLUSIONS We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known. PMID:23147524

  5. Helicobacter pylori: A Possible Risk Factor for Bone Health

    PubMed Central

    Chung, Yun Hee; Gwak, Jong Seop; Hong, Sung Woo; Hyeon, Jung Hyeon; Lee, Cheol Min; Oh, Seung Won

    2015-01-01

    Background Helicobacter pylori (H. pylori) infection may cause systemic inflammation and increase the production of tumor necrosis factor-α, interleukin-1, and interleukin-6. Unfortunately, bone mineral density also may be affected by these cytokines. This study aimed to evaluate the association between bone mineral density and H. pylori infection. Methods A cross-sectional study evaluated 1,126 men undergoing a comprehensive health screening in a private Korean screening center. Subjects' sera were tested for H. pylori antibodies (immunoglobulin G) using an enzyme-linked immunosorbent assay, and bone mineral densities (g/cm2) of the lumbar spine, femoral neck, and total femur were obtained using dual-energy X-ray absorptiometry. To evaluate the difference in bone mineral density according to H. pylori infection status, the adjusted mean bone mineral densities at each site were compared after adjusting for potential confounders, including age, sex, body mass index, smoking, alcohol consumption, and exercise. Results H. pylori infection was associated with a significant decrease in mean lumbar bone mineral density (H. pylori-positive, 1.190 g/cm2; H. pylori-negative, 1.219 g/cm2; P=0.006), which was greatest among men who were ≥50 years old (H. pylori-positive, 1.193 g/cm2; H. pylori-negative, 1.233 g/cm2; P=0.006). However, no significant association was observed in the bone mineral densities of the total femur and femoral neck. Conclusion In men, H. pylori infection was negatively associated with lumbar bone mineral density. This association may be useful in the early detection, prevention, and management of male osteoporosis. PMID:26435815

  6. Host pathogen interactions in Helicobacter pylori related gastric cancer

    PubMed Central

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  7. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    PubMed

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.

  8. A fluid model for Helicobacter pylori

    NASA Astrophysics Data System (ADS)

    Reigh, Shang-Yik; Lauga, Eric

    2015-11-01

    Swimming microorganisms and self-propelled nanomotors are often found in confined environments. The bacterium Helicobacter pylori survives in the acidic environment of the human stomach and is able to penetrate gel-like mucus layers and cause infections by locally changing the rheological properties of the mucus from gel-like to solution-like. In this talk we propose an analytical model for the locomotion of Helicobacter pylori as a confined spherical squirmer which generates its own confinement. We solve analytically the flow field around the swimmer, and derive the swimming speed and energetics. The role of the boundary condition in the outer wall is discussed. An extension of our model is also proposed for other biological and chemical swimmers. Newton Trust.

  9. [Clinical analysis of unsuccessful Helicobacter pylori eradication].

    PubMed

    Szadkowski, Aleksander; Chojnacki, Jan; Klupińska, Grazyna; Wojtuń, Stanisław

    2004-01-01

    Numerous medical reports claim that the effectiveness of H. pylori therapy decreases. The aim of the study was the analysis of the reasons of this phenomenon on own material. The study included 437 subjects, aged 19-64 years with chronic gastritis with H. pylori infection. All patients were subjected to: endoscopy, fast urease test, breath test (UBT-13C) and antibody titer in IgG class was determined. In the case of ineffective therapy bacteriological examination was performed. In the first stage of the therapy pantoprazol (2 x 40 mg) and amoxicillin (2 x 1000 mg) with metronidazol (2 x 500 mg) were applied in 282 subjects for 7 days (group I), amoxicillin with clarithromycin (2 x 500 mg) in 182 subjects (group II) and clarithromycin with metronidazol in 43 subjects (group III). After 6 weeks negative breath test was observed on average in 65.68% without significant differences between the groups. Ineffective therapy was more frequent in subjects over 45 years of age with high intensity of H. pylori colonization and earlier treated with antibiotics due to other reasons; such differences were not observed dependently on the antibody titer. In the second stage of the therapy pantoprazol was still administered but antibacterial drugs were changed among the groups. From among 150 subjects eradication was obtained in 117 (78.0%). In 33 subjects with ineffective therapy bacteriological examination of gastric bioptates confirmed antibiotic resistance in 75.76%. It results from the study that the applied therapy, consistent with current recommendations of the experts, does not ensure H. pylori eradication in part of the patients, what points to the necessity of searching for other effective antibiotics.

  10. OVERVIEW: DISINFECTION OF HELICOBACTER PYLORI AND AEROMONAS SPECIES

    EPA Science Inventory

    Helicobacter pylori and Aeromonas hydrophila are contaminants listed on the USEPA's 1998 Contaminant Candidate List (CCL).The sensitivity of H. pylori to chlorine and of Aeromonas spp. to inactivation by free chlorine, chloramine and ultraviolet (UV) was examined. Selective and...

  11. RECOVERY OF HELICOBACTER PYLORI FROM WATER BY IMMUNOMAGNETIC CAPTURE

    EPA Science Inventory

    A few reports have been written stating that H. pylori can be found in waters. However, detection and identification of H. pylori from water samples remains a very difficult task. One method that seems to work successfully is immunomagnetic capture. Water samples were concentr...

  12. Helicobacter pylori and oral pathology: relationship with the gastric infection.

    PubMed

    Adler, Isabel; Muiño, Andrea; Aguas, Silvia; Harada, Laura; Diaz, Mariana; Lence, Adriana; Labbrozzi, Mario; Muiño, Juan Manuel; Elsner, Boris; Avagnina, Alejandra; Denninghoff, Valeria

    2014-08-07

    Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.

  13. Biofilm formation enhances Helicobacter pylori survivability in vegetables.

    PubMed

    Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow

    2017-04-01

    To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment.

  14. Probiotics for the treatment of Helicobacter pylori infection in children

    PubMed Central

    Pacifico, Lucia; Osborn, John Frederick; Bonci, Enea; Romaggioli, Sara; Baldini, Rossella; Chiesa, Claudio

    2014-01-01

    The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H. pylori) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with antimicrobials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed. PMID:24574741

  15. SURVIVAL OF HELICOBACTER PYLORI IN A NATURAL FRESHWATER ENVIRONMENT

    EPA Science Inventory

    The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...

  16. Oral Cavity as an Extragastric Reservoir of Helicobacter pylori

    PubMed Central

    Anand, Pradeep S.; Kamath, Kavitha P.; Patil, Shankargouda; Preethanath, R. S.; Anil, Sukumaran

    2014-01-01

    Background. Several studies were reported on the prevalence, and relationship between the existence of Helicobacter pylori (H. pylori) in oral cavity and in stomach of patients. The purpose of this study was to systematically review the existing literature on the presence of H. pylori in the oral cavity and its link to gastric infection, the existence of coinfection, and the impact of anti-H. pylori therapy on the dental plaque and vice versa. Method. Two authors independently searched the Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies. The articles were analyzed critically and all qualified studies were included. The search was carried out by using a combined text and the MeSH search strategies: using the key words Helicobacter, Helicobacter pylori, and H. pylori in combination with dental plaque, periodontitis, and oral hygiene. Results. The data was presented in 8 tables and each topic separately discussed. Conclusion. Based on the systematic review of the available literature on H. pylori infection and its presence in the oral cavity, it can be concluded that dental plaque can act as a reservoir, and proper oral hygiene maintenance is essential to prevent reinfection. Due to the diversified methods and population groups involved in the available literature, no concrete evidence can be laid down. Further studies are necessary to establish the role of H. pylori in the oral cavity and its eradication on preventing the gastroduodenal infection. PMID:24701355

  17. Natural maternal transmission of H pylori in Mongolian gerbils

    PubMed Central

    Lee, Jin-Uk; Kim, Okjin

    2006-01-01

    AIM: To investigate maternal H pylori infection status to determine the potential of maternal transmission. METHODS: In the present study, we examined these issues in an experimental murine model, which is a Mongolian gerbil model that has been reported as an optimal laboratory animal model to study H pylori. Pregnant Mongolian gerbils, infected experimentally with H pylori, were divided into as four groups. Following the experimental design, the stomachs of the mother and litters were isolated and assessed for transmission of H pylori at the prenatal period, parturition day, 1-wk old and 3-wk old respectively. Bacterial culture and polymerase chain reaction (PCR) were used to examine the presence of transmitted H pylori. RESULTS: All litters showed no transmission of H pylori during pregnancy and at parturition day. However, they revealed 33.3% and 69.6% at 1-wk and 3-wk of age respectively by PCR. CONCLUSION: These results suggested that vertical infection during the prenatal period or delivery procedure is unlikely as a route of mother-to-child H pylori infection. It may be that H pylori is acquired through breast-feeding, contaminated saliva and fecal-oral transmission during co-habitation. PMID:17007019

  18. [Second Brazilian Consensus Conference on Helicobacter pylori infection].

    PubMed

    Coelho, Luiz Gonzaga Vaz; Zaterka, Schlioma

    2005-01-01

    Significant progress has been obtained since the First Brazilian Consensus Conference on H. pylori Infection held in 1995, in Belo Horizonte, MG, and justify a second meeting to establish updated guidelines on the current management of H. pylori infection. The Second Brazilian Consensus Conference on H. pylori Infection was organized by the Brazilian Federation of Gastroenterology and Brazilian Nucleus for the Study of Helicobacter and took place on June, 19-20, 2004 in São Paulo, SP. Thirty six delegates coming from 15 different Brazilian states including gastroenterologists, pathologists, microbiologists and pediatricians undertook the meeting. The participants were allocated in one the five main topics of the meeting: H. pylori and dyspepsia, H. pylori and NSAIDs, H. pylori and gastroesophageal reflux disease, H. pylori treatment, and H. pylori retreatment. Seventy per cent and more votes were considered as acceptance for the final statement. The results were presented during a special session on the VI Brazilian Week of Digestive System, in Recife, PE (October 2004), and this publication represents the summary of the main recommendations and conclusions emerged from the meeting.

  19. Probiotics for the treatment of Helicobacter pylori infection in children.

    PubMed

    Pacifico, Lucia; Osborn, John Frederick; Bonci, Enea; Romaggioli, Sara; Baldini, Rossella; Chiesa, Claudio

    2014-01-21

    The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H. pylori) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with antimicrobials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.

  20. Strategy for the treatment of Helicobacter pylori infection.

    PubMed

    Shiota, Seiji; Yamaoka, Yoshio

    2014-01-01

    The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin-based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance.

  1. Exploring alternative treatments for Helicobacter pylori infection.

    PubMed

    Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma

    2014-02-14

    Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy.

  2. H pylori recurrence after successful eradication

    PubMed Central

    Niv, Yaron

    2008-01-01

    Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative 13CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent. PMID:18330934

  3. Exploring alternative treatments for Helicobacter pylori infection

    PubMed Central

    Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma

    2014-01-01

    Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy. PMID:24587621

  4. Molecular Dynamics Study of Helicobacter pylori Urease.

    PubMed

    Minkara, Mona S; Ucisik, Melek N; Weaver, Michael N; Merz, Kenneth M

    2014-05-13

    Helicobacter pylori have been implicated in an array of gastrointestinal disorders including, but not limited to, gastric and duodenal ulcers and adenocarcinoma. This bacterium utilizes an enzyme, urease, to produce copious amounts of ammonia through urea hydrolysis in order to survive the harsh acidic conditions of the stomach. Molecular dynamics (MD) studies on the H. pylori urease enzyme have been employed in order to study structural features of this enzyme that may shed light on the hydrolysis mechanism. A total of 400 ns of MD simulation time were collected and analyzed in this study. A wide-open flap state previously observed in MD simulations on Klebsiella aerogenes [Roberts et al. J. Am. Chem. Soc.2012, 134, 9934] urease has been identified in the H. pylori enzyme that has yet to be experimentally observed. Critical distances between residues on the flap, contact points in the closed state, and the separation between the active site Ni(2+) ions and the critical histidine α322 residue were used to characterize flap motion. An additional flap in the active site was elaborated upon that we postulate may serve as an exit conduit for hydrolysis products. Finally we discuss the internal hollow cavity and present analysis of the distribution of sodium ions over the course of the simulation.

  5. Association between Helicobacter pylori status and metachronous gastric cancer after endoscopic resection

    PubMed Central

    Kim, Sung Bum; Lee, Si Hyung; Bae, Seung Il; Jeong, Yo Han; Sohn, Se Hoon; Kim, Kyeong Ok; Jang, Byung Ik; Kim, Tae Nyeun

    2016-01-01

    AIM To investigate the effect of Helicobacter pylori (H. pylori) status test and H. pylori eradication on the occurrence of metachronous gastric cancer (MGC) after endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) and risk factors of MGC. METHODS The authors retrospectively reviewed the medical records of 433 patients (441 lesions) who underwent ESD for EGC from January 2005 to January 2015 in Yeungnam University Hospital. Patients were categorized into two groups; the H. pylori tested group (n = 257) and the H. pylori non-tested group (n = 176) based on performance of H. pylori status test after ESD of EGC. The H. pylori tested group was further categorized into three subgroups based on H. pylori status; the H. pylori-eradicated subgroup (n = 120), the H. pylori-persistent subgroup (n = 42), and the H. pylori-negative subgroup (n = 95). Incidences of MGC and risk factors of MGC were identified. RESULTS Median follow-up duration after ESD was 30.00 mo (range, 6-107 mo). Total 15 patients developed MGC during follow-up. MGC developed in 11 patients of the H. pylori tested group (7 in the H. pylori-negative subgroup, 3 in the H. pylori-eradicated subgroup, and 1 in the H. pylori-persistent subgroup) and 4 patients of the H. pylori non-tested group (P > 0.05). The risk factors of MGC were endoscopic mucosal atrophy in the H. pylori tested group and intestinal metaplasia in all patients. CONCLUSION H. pylori eradication and H. pylori status test seems to have no preventive effect on the development of MGC after ESD for EGC. The risk factors of MGC development were endoscopic mucosal atrophy in the H. pylori tested group alone and intestinal metaplasia in all patients. PMID:27956803

  6. Identification of Helicobacter pylori in skin biopsy of prurigo pigmentosa.

    PubMed

    Missall, Tricia A; Pruden, Samuel; Nelson, Christine; Fohn, Laurel; Vidal, Claudia I; Hurley, M Yadira

    2012-06-01

    A 23-year-old Chinese man presented with a 3-year history of a pruritic eruption. On examination, pink urticarial papules associated with hyperpigmented reticulated patches were noted on his neck, back, and upper chest. Histopathology revealed vacuolar interface dermatitis and numerous gram-negative rods within a dilated hair follicle. The organisms were reactive with anti-Helicobacter pylori immunohistochemisty. The histologic findings and clinical presentation support the diagnosis of prurigo pigmentosa. Additional testing demonstrated a positive urease breath test and serum H. pylori IgG antibodies. The patient was referred to gastroenterology and treated with appropriate antibiotics. After treatment, esophagogastroduodenoscopy revealed chronic gastritis without evidence of H. pylori infection and his skin showed reticulated hyperpigmented patches without evidence of active inflammatory papules. Although previous reports have associated prurigo pigmentosa to H. Pylori gastritis, this is the first report of H. pylori organisms identified in a skin biopsy of prurigo pigmentosa.

  7. [Helicobacter pylori eradication therapy with omeprazole and amoxicillin: current status].

    PubMed

    Bayerdörffer, E; Miehlke, S; Mannes, G A

    1994-11-01

    Combined therapy with the proton pump inhibitor omeprazole and amoxicillin has become an important alternative in the treatment of ulcer disease associated with Helicobacter pylori infection. Due to the high efficacy in eradicating H.pylori, missing resistance of H.pylori against amoxicillin and high tolerability and digestibility this regimen may be recommended for widespread routine use. In a randomized, double-blind multicenter trial an H.pylori eradication rate of over 90% has been achieved for the first time by dual therapy using a daily omeprazole dose of 120 mg (3x40 mg) in combination with 3 x 750 mg amoxicillin for 14 days, which is comparable with classical triple therapy containing bismuth and two antibiotics. On the basis of an "intention-to-treat-analysis" dual therapy of omeprazole 3x40 mg + 3x750 mg amoxicillin is considered at present to be the most effective regimen for the treatment of H.pylori-associated diseases.

  8. Immunology and vaccines and nanovaccines for Helicobacter pylori infection.

    PubMed

    Milani, Morteza; Sharifi, Yaeghob; Rahmati-Yamchi, Mohammad; Somi, Mohammad H; Akbarzadeh, Abolfazl

    2015-06-01

    Helicobacter pylori infection is very common worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. Since the eradication requires treatment with multidrug regimens, prevention of primary infection by a suitable vaccine is attractive. Developing vaccines on the spot when and where an infection is breaking out might be possible, thanks to engineered nanoparticles. In this review, the nature of the host immune response to H. pylori infection is considered. We explain recent candidate vaccines and prophylactic or therapeutic immunization strategies for use against H. pylori. We also describe identification of different types of immune responses that may be related to protection against H. pylori infection. Thus, it seems that there is still a strong need to clarify the main protective immune response against H. pylori.

  9. Inhibition of Helicobacter pylori colonization by an antiulcer agent, sulglycotide.

    PubMed

    Czajkowski, A; Piotrowski, J; Yotsumoto, F; Slomiany, A; Slomiany, B L

    1993-04-01

    Sulglycotide, a potent antiulcer agent derived from duodenal mucus glycopeptide through sulfation of the carbohydrate moieties, was evaluated with respect to its ability to interfere with H. pylori mucosal attachment. H. pylori cells were incubated with sulglycotide or human gastric mucin and then examined for their inhibitory capacity of H. pylori attachment to erythrocytes. Titration data revealed that the mucin inhibitory activity was confined to its sulfomucin fraction, the titer of which was found to be 16-fold higher than that of intact mucin. The data with sulglycotide showed that the inhibitory titer of this agent against H. pylori attachment was at least 30-fold higher than that of the sulfated gastric mucin fraction. The results point towards the involvement of sulfomucins in the protection of gastric mucosa from H. pylori colonization and demonstrate that sulglycotide, because of structural similarities, is ideally suited to augment the inherent mucosal defenses against this pathogen.

  10. Helicobacter pylori does not release cysteamine into gastric juice.

    PubMed Central

    Leonard, M B; Neithercut, W D; Gillen, D; McColl, K E

    1997-01-01

    AIM: To determine whether Helicobacter pylori releases cysteamine into gastric juice as cysteamine is known to be ulcerogenic. METHODS: Samples of fasting gastric juice were collected from 22 individuals (four women); 10 subjects were H pylori negative. The presence of infection was confirmed by examination and culture of gastric biopsies. Cysteamine in gastric juice was measured by reversed phase gradient high performance liquid chromatography with a detection limit of 10 mumol/l. RESULTS: Cysteamine was not detected in any of the gastric juice samples or in extracts of cultured H pylori. CONCLUSIONS: If H pylori produces cysteamine then the amounts produced are insignificant and are unlikely to explain the association between H pylori infection and the development of duodenal ulcer disease. PMID:9389979

  11. The eradication treatments of Helicobacter pylori.

    PubMed

    Wermeille, J; Zelger, G; Cunningham, M

    1998-02-01

    The eradication of Helicobacter pylori is at present widely recognized as the adequate therapeutic approach for gastric and duodenal ulcers in infected patients. In those with dyspepsia but no ulcer as well as in those with type B chronic gastritis, eradication remains controversial. It is difficult to have a clear opinion on the advantages and disadvantages of the numerous existing therapies. Therefore, a systematic review of published treatments has been made by the authors. Ideally, the eradication treatment of H. pylori should have the following advantages: 1. eradication superior to 90%, 2. simplicity, 3. short duration, 4. safety, 5. low cost, 6. reproducibility of results. Dual therapies (2 antibiotics or a proton pump inhibitor in combination with an antibiotic) rarely allow an eradication greater than 90% and the results have poor reproducibility. Consequently, they do not represent an ideal anti-H. pylori treatment. Triple therapies come closer to the requirements for an ideal treatment, with eradication rates generally close to 90%, varying little between studies and the countries in which they were performed. The triple therapy bismuth-imidazole-tetracycline (or amoxicillin) still represents for many authors the standard reference therapy. It has the advantage of low cost, high efficacy and widespread use. It is the therapy that has been the most studied. However, the increasing emergence of strains resistant to imidazoles, the complexity of the treatment (10 to 12 tablets per day), the numerous adverse effects and the lack of availability of bismuth salts in certain countries has led to the elaboration of therapeutic schemes combining an antisecretory drug with 2 antibiotics. Among these, the combination PPI-clarithromycine-imidazole during 7 days represents the most studied triple therapy of short duration for some authors, it already represents a new standard. However, the efficacy of this therapy seems dependent on the sensitivity of the bacteria to

  12. Role of Helicobacter pylori in gastric cancer: Updates

    PubMed Central

    Khatoon, Jahanarah; Rai, Ravi Prakash; Prasad, Kashi Nath

    2016-01-01

    Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC. PMID:26909129

  13. Epidemiological study on food intake and Helicobacter pylori infection.

    PubMed

    Toyonaga, A; Okamatsu, H; Sasaki, K; Kimura, H; Saito, T; Shimizu, S; Fukuizumi, K; Tsuruta, O; Tanikawa, K; Sata, M

    2000-01-01

    We conducted an epidemiological study to investigate the relation of food intake to Helicobacter pylori (H. pylori) infection in an area endemic for H. pylori. In this study, 365 subjects, 104 men and 261 women, were randomly selected from 7,389 adult (over age 20) inhabitants of town A, Japan. The prevalence of immunoglobulin G (IgG) class antibody to H. pylori (anti-H. pylori) was 83.7% and the prevalence of anti-H. pylori increased with age significantly (P < 0.05). Subjects with anamnesis of gastritis, gastroduodenal ulcer and gastric cancer tended to have a higher anti-H. pylori positive ratio (93.5%) than those without (81.0%). But there was no relationship between anti-H. pylori prevalence and sex, blood type, smoking or drinking habits. Daily intake of foods by food groups, nutrients and the concentrations of serum ingredients were compared between 37 anti-H. pylori-positive and 40 negative subjects selected from 365 inhabitants by matching up according to sex and age. The daily intake of cereals, potatoes and starches, and milks tended to be higher in positive than negative subjects, while the daily intake of algae and tea appeared to be a little higher in negative than in positive subjects. The daily zinc intake of antibody-positive subjects was significantly higher (P < 0.05) than in antibody negative subjects. On the other hand, the daily iron intake in negative subjects was significantly higher (P < 0.05) than in positive subjects. The serum concentrations of copper, zinc, and vitamin E tended to be higher in positive than negative subjects. But there were no significant differences in serum ingredients concentrations between antibody negative and positive subjects. Our findings suggest that iron and zinc intakes may effect on H. pylori infection.

  14. Evaluation of Helicobacter pylori in reflux oesophagitis and Barrett's oesophagus.

    PubMed Central

    Newton, M; Bryan, R; Burnham, W R; Kamm, M A

    1997-01-01

    BACKGROUND: One of the major pathophysiological abnormalities in patients with gastro-oesophageal reflux disease is thought to involve transient lower oesophageal sphincter (LOS) relaxations. One component of the neural mechanism controlling the LOS appears to be a reflex are whose afferent limb originates in the gastric fundus. As inflammation is known to be associated with neural activation an investigation was made to determine whether gastric infection with H pylori is altered in prevalence or distribution in patients with reflux disease. METHODS: Five groups of subjects referred for endoscopy-group 1: 25 controls (asymptomatic individuals with anaemia and normal endoscopy); group 2: 36 subjects with erosive oesophagitis alone (Savary-Millar grades I-III); group 3: 16 subjects with duodenal ulcer alone; group 4: 15 subjects with oesophagitis with duodenal ulcer; group 5: 16 subjects with Barrett's oesophagus. No patients were receiving acid suppressants or antibiotics. An antral biopsy specimen was taken for a rapid urease test, and two biopsy specimens were taken from the antrum, fundus, and oesophagus (inflamed and non-inflamed) for histological evidence of inflammation and presence of H pylori using a Giemsa stain. RESULTS: Nine (36%) controls had H pylori. Patients with duodenal ulcer alone had a significantly higher incidence of colonisation by H pylori than other groups (duodenal ulcer 15 (94%); oesophagitis 13 (36%); oesophagitis+duodenal ulcer 6 (40%); Barrett's oesophagus 4 (25%)). H pylori was not more common in oesophagitis. When H pylori colonised the gastric antrum it was usually found in the gastric fundus. There was no difference in anatomical distribution of H pylori in the different patient groups. In Barrett's oesophagus H pylori was found in two of 16 in the metaplastic epithelium. CONCLUSION: H pylori is not more common and its distribution does not differ in those with oesophagitis compared with control subjects, and is therefore unlikely

  15. Persistence of Helicobacter pylori in heterotrophic drinking-water biofilms.

    PubMed

    Gião, M S; Azevedo, N F; Wilks, S A; Vieira, M J; Keevil, C W

    2008-10-01

    Although the route of transmission of Helicobacter pylori remains unknown, drinking water has been considered a possible transmission vector. It has been shown previously that, in water, biofilms are a protective niche for several pathogens, protecting them from stressful conditions, such as low carbon concentration, shear stress, and less-than-optimal temperatures. In this work, the influence of these three parameters on the persistence and cultivability of H. pylori in drinking-water biofilms was studied. Autochthonous biofilm consortia were formed in a two-stage chemostat system and then inoculated with the pathogen. Total numbers of H. pylori cells were determined by microscopy using a specific H. pylori 16S rRNA peptide nucleic acid probe, whereas cultivable cells were assessed by standard plating onto selective H. pylori medium. Cultivable H. pylori could not be detected at any time point, but the ability of H. pylori cells to incorporate, undergo morphological transformations, persist, and even agglomerate in biofilms for at least 31 days without a noticeable decrease in the total cell number (on average, the concentration was between 1.54 x 10(6) and 2.25 x 10(6) cells cm(-2)) or in the intracellular rRNA content may indicate that the loss of cultivability was due to entry into a viable but noncultivable state. Unlike previous results obtained for pure-culture H. pylori biofilms, shear stress did not negatively influence the numbers of H. pylori cells attached, suggesting that the autochthonous aquatic bacteria have an important role in retaining this pathogen in the sessile state, possibly by providing suitable microaerophilic environments or linking biomolecules to which the pathogen adheres. Therefore, biofilms appear to provide not only a safe haven for H. pylori but also a concentration mechanism so that subsequent sloughing releases a concentrated bolus of cells that might be infectious and that could escape routine grab sample microbiological

  16. High antibiotic resistance rate: A difficult issue for Helicobacter pylori eradication treatment.

    PubMed

    Zhang, Mei

    2015-12-28

    Helicobacter pylori (H. pylori) infection is associated with a variety of upper gastrointestinal diseases, including gastric cancer. With the wide application of antibiotics in H. pylori eradication treatment, drug-resistant strains of H. pylori are increasing. H. pylori eradication treatment failure affects the outcome of a variety of diseases of the upper gastrointestinal tract. Therefore, antibiotic resistance that affects H. pylori eradication treatment is a challenging situation for clinicians. The ideal H. pylori eradication therapy should be safe, effective, simple, and economical. The eradication rate of triple antibiotic therapy is currently less than 80% in most parts of the world. Antibiotic resistance is the main reason for treatment failure, therefore the standard triple regimen is no longer suitable as a first-line treatment in most regions. H. pylori eradication treatment may fail for a number of reasons, including H. pylori strain factors, host factors, environmental factors, and inappropriate treatment.

  17. Advances in diagnosis and treatment of Helicobacter pylori infection.

    PubMed

    Ranjbar, Reza; Behzadi, Payam; Farshad, Shohreh

    2017-03-06

    Helicobacter pylori is a Gram-negative motile bacterium causative agent of acute and chronic digestive and extra-digestive human infections. According to different reports worldwide, H. pylori symptomatic and asymptomatic infections are a global problem. The statistical investigations show a percentage of 50 for people who are involved in H. pylori acute/chronic digestive and/or extra-digestive infections around the world. This review focuses on digestive and extra-digestive diseases caused by H. pylori, the related virulence factors, diagnostic techniques including non-invasive and invasive diagnostics and treatment. There is an abundance of diagnostics for detection and identification of H. pylori. The availability, cost, and the condition of test performance may differ from place to place. To increase the level of reliability in association with diagnostic tools for detecting H. pylori, several techniques must be applied at once as multi-diagnostic technique. Furthermore, there are several pharmacotherapies which can be used for complete eradication of H. pylori infection.

  18. Treatment of Helicobacter pylori infection: Current and future insights

    PubMed Central

    Safavi, Maliheh; Sabourian, Reyhaneh; Foroumadi, Alireza

    2016-01-01

    Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects. PMID:26798626

  19. Lipid Profile in Cardiac Syndrome X: Association with Helicobacter pylori

    PubMed Central

    Zeynalzadeh, Javad; Shirpoor, Alireza; Seyedmohammadzad, Mirhossein; Hajhosseini, Reza

    2016-01-01

    Introduction Chronic inflammation caused by Helicobacter pylori (H.pylori) infection has a pathogenic role in Cardiac Syndrome X (CSX). In addition, it has shown that bacterial infection may affect blood lipids. Aim To assess if H.pylori affects the level of lipid profile in CSX. Materials and Methods Eighty-eight CSX patients and 97 healthy controls were enrolled. The Total Cholesterol (TC), Triglyceride (TG), Lipoprotein A (LP{A}), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Apoprotein A1 (APOA1), and Apoprotein B (APOB) was estimated colorimetrically. In addition, the presence of IgG antibody to H.pylori was tested in plasma samples by using enzyme linked immunosorbent assay method. Results TC, LP{A}, LDL, APOA1 and APOB levels in CSX group were significantly higher than those of the control group (p<0.05). But, these parameters in H.pylori positive and H.pylori negative, among CSX and control groups were not significant. Conclusion Increased plasma level of lipid profile and H.pylori infection were associated with CSX; it seems that plasma lipid disorders have a significant role in the development of CSX. PMID:27630835

  20. Serologic Evidence for Fecal–Oral Transmission of Helicobacter pylori

    PubMed Central

    Bui, David; Brown, Heidi E.; Harris, Robin B.; Oren, Eyal

    2016-01-01

    Helicobacter pylori infection is among the most prevalent infections in the world and a key cause of gastric diseases; however, its route of transmission remains unclear. This study aimed to assess the potential for fecal–oral transmission of H. pylori by leveraging its association with a disease with known etiology. Utilizing serology data from the National Health and Nutrition Examination Survey (NHANES 1999; N = 6,347), the association between H. pylori and hepatitis A virus (HAV), a sensitive indicator for fecal–oral exposure, was assessed. Survey-weighted kappa and multiple logistic regression were used to quantify the association between H. pylori and HAV after controlling for age, sex, race, poverty, birthplace, crowding, smoking, and alcohol use. Concordant serological results were found among 69.8% of participants (survey-weighted κ = 0.30, 95% confidence interval [CI] = 0.26, 0.35). The adjusted odds of H. pylori seropositivity were over two times higher after adjusting for confounders (odds ratio = 2.27, 95% CI = 1.79, 2.87). Results from this study suggest H. pylori and HAV infections are strongly associated. Since HAV is primarily transmitted through the fecal–oral route, fecal–oral transmission may be an important pathway for H. pylori spread. PMID:26598563

  1. Helicobacter pylori seropositivity in subjects with acute myocardial infarction.

    PubMed Central

    Rathbone, B.; Martin, D.; Stephens, J.; Thompson, J. R.; Samani, N. J.

    1996-01-01

    OBJECTIVE: To determine whether Helicobacter pylori infection increases the risk of myocardial infarction. DESIGN: Case-control study. SETTING: University teaching hospital. METHODS: Serological evidence of H pylori infection was determined in 342 consecutive patients with acute myocardial infarction admitted into the coronary care unit and in 236 population-based controls recruited from visitors to patients on medical and surgical wards. RESULTS: 206/342 (60.2%) of cases were H pylori positive compared with 132/236 (55.9%) of controls (P = 0.30). Age and sex stratified odds ratio for myocardial infarction associated with H pylori seropositivity was 1.05 (95% CI 0.7 to 1.53, P = 0.87) and this remained non-significant (P = 0.46) when other risk factors for ischaemic heart disease were taken into account using logistic regression analysis. H pylori seropositivity was not associated with several coronary risk factors in either cases or controls. CONCLUSION: No increase was found in H pylori seropositivity in subjects with acute myocardial infarction. This suggests that previous H pylori infection is not a major risk factor for acute myocardial infarction. Images PMID:8983674

  2. Evolution of the Selenoproteome in Helicobacter pylori and Epsilonproteobacteria

    PubMed Central

    Cravedi, Pietro; Mori, Giulia; Fischer, Frédéric; Percudani, Riccardo

    2015-01-01

    By competing for the acquisition of essential nutrients, Helicobacter pylori has the unique ability to persist in the human stomach, also causing nutritional insufficiencies in the host. Although the H. pylori genome apparently encodes selenocysteine synthase (SelA, HP1513), a key pyridoxal phosphate (PLP)-dependent enzyme for the incorporation of selenium into bacterial proteins, nothing is known about the use of this essential element in protein synthesis by this pathogen. We analyzed the evolution of the complete machinery for incorporation of selenium into proteins and the selenoproteome of several H. pylori strains and related Epsilonproteobacteria. Our searches identified the presence of selenoproteins—including the previously unknown DUF466 family—in various Epsilonproteobacteria, but not in H. pylori. We found that a complete system for selenocysteine incorporation was present in the Helicobacteriaceae ancestor and has been recently lost before the split of Helicobacter acinonychis and H. pylori. Our results indicate that H. pylori, at variance with other gastric and enterohepatic Helicobacter, does not use selenocysteine in protein synthesis and does not use selenium for tRNA wobble base modification. However, selA has survived as a functional gene, having lost the domain for the binding of selenocysteine tRNA, but maintaining the ability to bind the PLP cofactor. The evolutionary modifications described for the SelA protein of H. pylori find parallels in other bacterial and archaeal species, suggesting that an alternative enzymatic function is hidden in many proteins annotated as selenocysteinyl-tRNA synthase. PMID:26342139

  3. Helicobacter pylori and Antibiotic Resistance, A Continuing and Intractable Problem.

    PubMed

    Hu, Yue; Zhang, Meng; Lu, Bin; Dai, Jinfeng

    2016-10-01

    Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti-H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation-reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered.

  4. Anti-Helicobacter pylori Potential of Artemisinin and Its Derivatives

    PubMed Central

    Goswami, Suchandra; Chinniah, Annalakshmi; Pal, Anirban; Kar, Sudip K.

    2012-01-01

    The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative β-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC90, and minimum bactericidal concentration range values of 0.25 to 1.0 μg/ml, 1.0 μg/ml, and 1 to 16 μg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, β-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted. PMID:22687518

  5. Structure, function and localization of Helicobacter pylori urease.

    PubMed Central

    Dunn, B. E.; Phadnis, S. H.

    1998-01-01

    Helicobacter pylori is the causative agent of most cases of gastritis. Once acquired, H. pylori establishes chronic persistent infection; it is this long-term infection that, is a subset of patients, leads to gastric or duodenal ulcer, gastric cancer or gastric MALT lymphoma. All fresh isolates of H. pylori express significant urease activity, which is essential to survival and pathogenesis of the bacterium. A significant fraction of urease is associated with the surface of H. pylori both in vivo and in vitro. Surface-associated urease is essential for H. pylori to resist exposure to acid in the presence of urea. The mechanism whereby urease becomes associated with the surface of H. pylori is unique. This process, which we term "altruistic autolysis," involves release of urease (and other cytoplasmic proteins) by genetically programmed autolysis with subsequent adsorption of the released urease onto the surface of neighboring intact bacteria. To our knowledge, this is the first evidence of essential communal behavior in pathogenic bacteria; such behavior is crucial to understanding the pathogenesis of H. pylori. PMID:10378351

  6. Role of Helicobacter pylori infection on nutrition and metabolism

    PubMed Central

    Franceschi, Francesco; Annalisa, Tortora; Teresa, Di Rienzo; Giovanna, D’Angelo; Ianiro, Gianluca; Franco, Scaldaferri; Viviana, Gerardi; Valentina, Tesori; Riccardo, Lopetuso Loris; Antonio, Gasbarrini

    2014-01-01

    Helicobacter pylori (H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world’s population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome. PMID:25278679

  7. In vitro antagonistic activity of Lactobacillus casei against Helicobacter pylori

    PubMed Central

    Enany, Shymaa; Abdalla, Salah

    2015-01-01

    Helicobacter pylori is one of the most common causes of chronic infections in humans. Curing H. pylori infection is difficult because of the habitat of the organism below the mucus adherent layer of gastric mucosa. Lactobacilli are known as acid-resistant bacteria and can remain in stomach for a long time than any other organism, we aimed in this study to examine the efficacy of Lactobacillus casei as a probiotic against H. pylori in humans. Particularly, L. casei was opted as it is considered to be one of the widely used probiotics in dairy products. One hundred and seven strains of H. pylori were isolated from dyspeptic patients and were tested for their antibiotic susceptibility to metronidazole (MTZ), clarithromycin (CLR), tetracycline (TET), and amoxicillin (AMX) by the disc diffusion method. The strains were examined for their susceptibility toward L. casei - present in fermented milk products - by well diffusion method. It was found that 74.7% strains were resistant to MTZ; 1.8% to MTZ, TET, and CLR; 3.7% to MTZ and CLR; 4.6% to MTZ and TET; and 0.9% were resistant to MTZ, TET, and AMX. The antibacterial activity of L. casei against H. pylori was determined on all the tested H. pylori isolates including antibiotic resistant strains with different patterns. Our study proposed the use of probiotics for the treatment of H. pylori infection as an effective approach. PMID:26691482

  8. Gastroprotective agents in mucosal defense against Helicobacter pylori.

    PubMed

    Slomiany, B L; Murty, V L; Piotrowski, J; Slomiany, A

    1994-09-01

    1. Convincing evidence now exists that infection with H. pylori plays a major role in the pathogenesis of gastric disease. Having a niche bordering two major perimeters of mucosal defenses, the bacterium apparently exerts its detrimental effect on the mucus layer as well as the gastric epithelium. Therefore, gastroprotective agents capable of counteracting these detrimental effects of H. pylori are gaining importance in the treatment of gastric disease. 2. The colonization of gastric mucosa by H. pylori involves specific glycolipid receptors bearing acidic substituents, a process inhibited by gastric sulfomucins. Two antiulcer agents bearing sulfated sugar groups have been demonstrated to possess the ability to interfere with H. pylori colonization process. These are sucralfate and sulglycotide. The two agents are also potent inhibitors of H. pylori glycosulfatase activity directed against indigenous mucosal defenses. 3. A variety of extracellular enzymes such as proteases, lipases and phospholipases, elaborated by H. pylori cause the weakening of the integrity of gastric mucus coat and render the underlying epithelium vulnerable to noxious luminal contents. Among the most potent agents capable of countering the proteolytic activity of H. pylori are nitecapone, ebrotidine and sulglycotide, while ebrotidine and sulglycotide were found to be most effective inhibitors of H. pylori lipolytic activities. 4. The gastric epithelial integrity is compromized by the H. pylori cell-wall lipopolysaccharide untoward effect on the epithelial surface receptors. The interference of the lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding.

  9. Helicobacter pylori associated Asian enigma: Does diet deserve distinction?

    PubMed Central

    Zaidi, Syed Faisal

    2016-01-01

    Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world’s population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with

  10. Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia?

    PubMed Central

    Mearin, F; de Ribot, X; Balboa, A; Salas, A; Varas, M J; Cucala, M; Bartolomé, R; Armengol, J R; Malagelada, J R

    1995-01-01

    The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension. PMID:7672680

  11. Helicobacter pylori associated Asian enigma: Does diet deserve distinction?

    PubMed

    Zaidi, Syed Faisal

    2016-04-15

    Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world's population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with

  12. A study of recombinant protective H. pylori antigens

    PubMed Central

    Jiang, Zheng; Tao, Xiao-Hong; Huang, Ai-Long; Wang, Pi-Long

    2002-01-01

    AIM: To construct a recombinant vector which can express Mr26000 outer membrane protein (OMP) from Helicobacter pylori (H. pylori), and to obtain the vaccine protecting against H. pylori infection and a diagnostic reagent kit quickly detecting H. pylori infection. METHODS: The gene encoding the structural Mr26000 outer membrane protein of H. pylori was amplified from H. pylori chromosomal DNA by PCR, and inserted in the prokaryotic expression vector pET32a(+), which was transformed into the Top10 E. coli strain. Recombinant vector was selected, identified and transformed into BL-21(DE3) E. coli strain. The recombinant fusion proteins were expressed. The antigenicity of recombinant protein was studied by ELISA or immunoblotting and immunized Balb/c mice. RESULTS: The gene of Mr26000 OMP was amplified to be 594 base pairs, 1.1% of the cloned genes was mutated and 1.51% of amino acid residues was changed, but there was homogeneity between them. The recombinant fusion protein encoded objective polypeptides of 198 amino acid residues, corresponding to calculated molecular masses of Mr26000. The level of soluble expression products was about 38.96% of the total cell protein. After purification by Ni-NTA agarose resin columniation, the purity of objective protein became about 90%. The ELISA results showed that recombinant fusion protein could be recognized by patient serum infected with H. pylori and rabbit serum immunized with the recombinant protein. Furthermore, Balb/c mice immunized with the recombinant protein were protected against H. pylori infection. CONCLUSION: Mr26000 OMP may be a candidate vaccine preventing H. pylori infection. PMID:11925614

  13. Optimizing enrichment culture conditions for detecting Helicobacter pylori in foods.

    PubMed

    Jiang, Xiuping; Doyle, Michael P

    2002-12-01

    The survival and growth of Helicobacter pylori under enrichment conditions in fresh, autoclaved and irradiated ground beef were determined. H. pylori grew in autoclaved ground beef at 37 degrees C under microaerobic conditions in brain heart infusion broth with 7% horse serum at pH 7.3 after 3 to 7 days of lag time but did not grow within 7 days in irradiated (10 kGy) ground beef under the same enrichment conditions. Adjustment of the enrichment broth to pH 5.5 enabled the growth (ca. 2 log10 CFU/ml) of H. pylori within 7 days in the presence of irradiated ground beef and the prolific growth (ca. 3 to 4 log10 CFU/ml) of H. pylori within 3 days in the presence of autoclaved beef. H. pylori in fresh ground beef could not be isolated from enrichment media with antibiotics; however. H. pylori ureA could be detected by polymerase chain reaction (PCR) in such enrichment media after 1 to 3 days of incubation at 37 degrees C. The addition of supplements, i.e., 0.3% mucin, 0.05% ferrous sulfate, and 0.05% sodium pyruvate or 0.008 M urea, or the adjustment of the enrichment broth pH to 5.5 or 4.5 enabled the detection of H. pylori ureA in enrichment media incubated for 1, 2, 3, and/or 7 days at 37 degrees C. H. pylori in sterile milk refrigerated at 4 degrees C at an initial level of 10(6) CFU/ml was inactivated to an undetectable level within 6 days; however, H. pylori was not detected either by a PCR assay or by the plating of enrichment cultures of 120 raw bovine milk samples.

  14. Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori.

    PubMed

    Marone, P; Bono, L; Leone, E; Bona, S; Carretto, E; Perversi, L

    2001-12-01

    In this study we evaluated the antibacterial activity of mastic gum, a resin obtained from the Pistacia lentiscus tree, against clinical isolates of Helicobacter pylori. The minimal bactericidal concentrations (MBCs) were obtained by a microdilution assay. Mastic gum killed 50% of the strains tested at a concentration of 125 microg/ml and 90% at a concentration of 500 microg/ml. The influence of sub-MBCs of mastic gum on the morphologies of H. pylori was evaluated by transmission electron microscopy. The lentiscus resin induced blebbing, morphological abnormalities and cellular fragmentation in H. pylori cells.

  15. Immune Homeostasis of Human Gastric Mucosa in Helicobacter pylori Infection.

    PubMed

    Reva, I V; Yamamoto, T; Vershinina, S S; Reva, G V

    2015-05-01

    We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.

  16. Helicobacter pylori-associated idiopathic thrombocytopenic purpura: a narrative review.

    PubMed

    Franchini, Massimo; Vescovi, Pier Paolo; Garofano, Massimo; Veneri, Dino

    2012-07-01

    The Gram-negative bacterium Helicobacter pylori has a well-demonstrated role in several gastroduodenal diseases, including peptic ulcer disease, chronic active gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In addition, more recently, several studies have focused on the possible causal role of H. pylori in various extragastric disorders, such as cardiovascular, respiratory, neurological, skin, and autoimmune conditions. The current status of the research on the pathogenesis, clinical and therapeutic aspects of H. pylori-associated idiopathic thrombocytopenic purpura in adults and children will be addressed in this narrative review.

  17. [Relation between Helicobacter pylori and atopic diseases].

    PubMed

    López Pérez, Gerardo; Alcántara Rodríguez, Fernando

    2002-01-01

    The rise in the incidence of atopic diseases in the last years is associated to a greater prevalence of viral and bacterial infections. The infections facilitate a chronic inflammatory process that is directly related to the sensibilization of mast cells which favors manifestations of allergic diseases. Within the proposed bacteriological agents as causes of is Helicobacter pylori. This work is a bibliographical revision and concludes that there is not evidence of the direct causal relation between infection by Helicobacter and allergic diseases; however, it can play an indirect role. Controlled and randomized studies are necessary to know accurately this relation because the eradication treatment could be a real alternative in these patients handling.

  18. Association between Parkinson's Disease and Helicobacter Pylori

    PubMed Central

    Oğuz, Sıdıka

    2016-01-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  19. Rapid improvement of Henoch-Schonlein purpura associated with the treatment of Helicobacter pylori infection

    PubMed Central

    Ulas, Turgay; Tursun, Irfan; Dal, Mehmet Sinan; Eren, Mehmet Ali; Buyukhatipoglu, Hakan

    2012-01-01

    Helicobacter pylori (H. pylori) are one of the most common bacterial infections, seen in humans, worldwide and their possible relationships to different diseases are a focus of attention nowadays. H. pylori may cause some extra intestinal manifestations some of which are dermatological conditions, including Henoch-Schönlein purpura (HSP), chronic urticaria and atopic dermatitis. We describe a 49-year-old man who presented with HSP triggered by gastric H. pylori infection. Treatment of H. Pylori infection was accompanied by prompt resolution of the gastrointestinal manifestations and purpuric rashes. These findings suggest a causative role for H. pylori in the occurrence of HSP. PMID:23833587

  20. Diagnostic methods for Helicobacter pylori detection and eradication

    PubMed Central

    Goddard, A F; Logan, R P H

    2003-01-01

    Helicobacter pylori is the principal cause of peptic ulcer disease and an important risk factor for the development of gastric cancer. The efficacy of 1 week triple therapies, which often have eradication rates of > 90%, is undermined by poor patient compliance and bacterial antimicrobial resistance. The development of new anti-H. pylori therapies presents enormous challenges to clinical pharmacologists, not only in the identification of novel targets, but also in ensuring adequate drug delivery to the unique gastric mucus niche of H. pylori. Animal models of H. pylori infection have been developed but their clinical validity has yet to be established. Vaccination, to prevent or treat infection, has been demonstrated in animal models, but human studies have not been so encouraging. PMID:12919175

  1. The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

    PubMed Central

    Sheh, Alexander; Fox, James G

    2013-01-01

    The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values < 4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota. PMID:23962822

  2. [Role of Helicobacter pylori coccoid forms in infection and recrudescence].

    PubMed

    Sarem, Muhannad; Corti, Rodolfo

    2016-01-01

    Helicobacter pylori is a spiral Gram-negative bacillus, which colonizes the human stomach and plays a key role in the pathogenesis of a number of gastroduodenal diseases. However, when expose to environmental stressed conditions, such as increased oxygen tension, extended incubation and exposure to antibiotics, Helicobacter pylori is able to entering the viable but nonculturable state, in which the bacterium modifies its morphology from a spiral to coccoid form, as a manifestation of cell adaptation to these adverse conditions. In gastric tissues, viable coccoid forms may remain latent for long time and retain virulence factors, so these forms possibly contribute to the treatment failures and recurrence of Helicobacter pylori infection and gastroduodenal diseases as well. In this review, we will discuss several aspects of cellular adaptation and survival of Helicobacter pylori, antibiotic susceptibility and virulence of coccoid forms and its involvement with recrudescence.

  3. Individual and combined effects of foods on Helicobacter pylori growth.

    PubMed

    Keenan, Jacqueline I; Salm, Nina; Hampton, Mark B; Wallace, Alison J

    2010-08-01

    Eradication of H. pylori can reduce the risk of non-cardia gastric cancer developing in infected humans. Thus, the consumption of foods that inhibit the growth of these bacteria may provide an alternative to current therapies that include antibiotics, proton pump inhibitors and/or bismuth salts. This study describes a simple broth dilution assay developed to screen a range of foods for their individual and combined effects on H. pylori growth. It was found that foods with measurable anti-H. pylori activity have an effect greater in combination than the sum of foods tested singly, and that this was most noticeable with a combination of broccoli sprouts and blackcurrant oil. The results suggest that food synergy should be considered in any nutraceutical approach to H. pylori infection.

  4. Antibacterial activity of Chamomilla recutita oil extract against Helicobacter pylori.

    PubMed

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarov, Valery G; Kvetnaya, Asya S

    2008-02-01

    The antibacterial activity of an oil extract of Chamomilla recutita flowers against Helicobacter pylori (H. pylori) was evaluated by the agar dilution method using Colombia agar with 10% sheep blood, an inoculum of McFarland 0.5 and incubation in an anaerobic atmosphere at 37 degrees C for 3 days. The oil extract was prepared by olive oil extraction of Chamomilla recutita flowers using rotary pulsation. The MIC(90) (minimal inhibitory concentration) and MIC(50) were 125 mg/mL and 62.5 mg/mL, respectively. It was shown that the Chamomilla recutita oil extract inhibited the production of urease by H. pylori. In addition, it was found that the morphological and fermentative properties of H. pylori were affected by application of the Chamomilla recutita oil extract.

  5. Discovery – The Link to H.Pylori Bacteria

    Cancer.gov

    NCI supported research to solidify the link between H. pylori infections and stomach cancer. As a result, new cancer treatment and prevention strategies are being developed, encouraging scientists to carefully examine other cancers for viral and bacterial connections.

  6. Recent Acquisition of Helicobacter pylori by Baka Pygmies

    PubMed Central

    Montano, Valeria; Maady, Ayas; Nkwescheu, Armand; Siri, Jose; Elamin, Wael F.; Falush, Daniel; Linz, Bodo; Achtman, Mark; Moodley, Yoshan; Suerbaum, Sebastian

    2013-01-01

    Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations

  7. Infection with Helicobacter pylori Is Associated with Protection against Tuberculosis

    PubMed Central

    Perry, Sharon; de Jong, Bouke C.; Solnick, Jay V.; la Luz Sanchez, Maria de; Yang, Shufang; Lin, Philana Ling; Hansen, Lori M.; Talat, Najeeha; Hill, Philip C.; Hussain, Rabia; Adegbola, Richard A.; Flynn, JoAnne; Canfield, Don; Parsonnet, Julie

    2010-01-01

    Background Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings We first examined M. tuberculosis-specific IFN-γ and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-γ responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36–0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63–2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12–0.80], p = 0.04). Conclusions/Significance H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for

  8. Biofilm and Helicobacter pylori: from environment to human host.

    PubMed

    García, Apolinaria; Salas-Jara, María José; Herrera, Carolina; González, Carlos

    2014-05-21

    Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively colonizes the human gastric epithelium. Over 50% of the world population is infected with H. pylori reaching up to 90% of infected individuals in developing countries. Nonetheless the increased impact upon public health care, its reservoir and the transmission pathway of the species has not been clearly established yet. Molecular studies allowed the detection of H. pylori in various aquatic environments, even forming biofilm in tap water distribution systems in several countries, suggesting a role of water as a possible reservoir of the pathogen. The persistence of human infection with H. pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the last years, experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents. However, only two anti- H. pylori biofilm disrupting agents have been successfully used: Curcumin - a natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory diseases. The main goal of this review was to discuss the evidences available in the literature supporting the ability of H. pylori to form biofilm upon various surfaces in aquatic environments, both in vivo and in vitro. The results published and our own observations suggest that the ability of H. pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans, mainly through natural water sources and water distribution systems.

  9. Heliobactor pylori Virulence Factors and Their Role in Pathogenesis

    DTIC Science & Technology

    2011-03-25

    pylori infection in children living in communal apartments as compared to children with traditional families (212). Transmission is also thought...isolated from the stomach and dental plaque (56, 99, 318). However, the rate of isolation of H. pylori from dental plaque is extremely low (39, 54, 56...99, 318), and PCR detection rates in dental plaque vary (224). Interestingly, dental workers do not have an increased rate of infection (194, 207

  10. One week's anti-Helicobacter pylori treatment for duodenal ulcer.

    PubMed Central

    Logan, R P; Gummett, P A; Misiewicz, J J; Karim, Q N; Walker, M M; Baron, J H

    1994-01-01

    This open study tested whether eradication of Helicobacter pylori (H pylori) heals duodenal ulcers as well as decreasing recurrence. H pylori was detected in patients with endoscopic duodenal ulcers by histology, CLO-test, culture, and 13C-urea breath test (13C-UBT). Tripotassium dicitrato bismuthate (120 mg) and amoxycillin (500 mg) each four times daily, were given for seven days, with 400 mg metronidazole five times a day on days 5-7. The 13C-UBT was repeated immediately after treatment and endoscopy repeated within 21 days. After treatment unhealed ulcers were reinspected one month later and healed ulcers followed up by 13C-UBT alone for 12 months. Of 45 patients, 44 were available for follow up. Mean pretreatment excess delta 13CO2 excretion was 25.6 per mil, which fell to 2.4 per mil immediately after finishing treatment, indicating clearance of H pylori in every patient. At the second endoscopy (median interval 20 days from start of treatment) 33 of 44 (75%) duodenal ulcers had healed. Ten of the remaining 11 duodenal ulcers were smaller and those 10 healed in the next two weeks with no further treatment. Two patients' ulcers that initially healed with clearance of H pylori recurred three weeks later (both had metronidazole resistant H pylori). H pylori was eradicated in 28 of 44 (64%) patients (13C-UBT negative for median follow up 10.2 months). Overall 41 of 43 (93%, 95% confidence intervals 81%-99%) duodenal ulcers were healed at one month. This study suggests that one week of anti-H pylori triple treatment is effective in healing duodenal ulcers. PMID:8307442

  11. Relatedness of Helicobacter pylori populations to gastric carcinogenesis

    PubMed Central

    Dong, Quan-Jiang; Zhan, Shu-Hui; Wang, Li-Li; Xin, Yong-Ning; Jiang, Man; Xuan, Shi-Ying

    2012-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrica1, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and possibly result from geographical separation of the bacterium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different populations of H. pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H. pylori. Further studies are indicated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals. PMID:23236231

  12. Helicobacter Pylori Gastritis, a Presequeale to Coronary Plaque

    PubMed Central

    Raut, Shrikant C.; Patil, Vinayak W.; Dalvi, Shubhangi M.; Bakhshi, Girish D.

    2015-01-01

    Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student’s t-test, Pearson’s correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology. PMID:25918633

  13. Age of the Association between Helicobacter pylori and Man

    PubMed Central

    Bond, Robert P.; Nieuwoudt, Martin; Soodyall, Himla; Schlebusch, Carina M.; Bernhöft, Steffi; Hale, James; Suerbaum, Sebastian; Mugisha, Lawrence; van der Merwe, Schalk W.; Achtman, Mark

    2012-01-01

    When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya. PMID:22589724

  14. Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

    PubMed Central

    Yoon, Kichul; Kim, Nayoung; Kim, Jaeyeon; Lee, Jung Won; Lee, Hye Seung; Lee, Jong-Chan; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung Ho; Lee, Yoon Jin; Lee, Kyoung-Ho; Kim, Young-Hoon; Lee, Dong Ho

    2017-01-01

    Background/Aims Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. pylori status. Methods Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively. Results One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group. Conclusions A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori. PMID:27840366

  15. New transport medium for cultural recovery of Helicobacter pylori.

    PubMed

    Cellini, Luigina; Di Campli, Emanuela; Di Bartolomeo, Soraya; Bessa, Lucinda Janete; Baffoni, Marina; Di Giulio, Mara

    2014-12-01

    We developed a new transport medium (GESA--Helicobacter pylori transport medium [publication no. WO/2014/019696, patent pending no. PCT/EP2013/002292; Liofilchem s.r.l., Roseto degli Abruzzi, Teramo, Italy]) for recovery of Helicobacter pylori from gastric biopsy samples. GESA transport medium, in a semisolid state, provides the optimal conditions for maintaining the viability of the microorganism over time. The efficacy of the transport medium was assessed through in vitro and ex vivo experiments. We were able to recover different suspensions of H. pylori ATCC 43629 and H. pylori 13 A in GESA transport medium stored at 4 °C for up to 10 days. In particular, with a starting inoculum of ∼ 10(5) CFU, after 7 days of storage, 150 ± 25 CFU and 40 ± 7 CFU of the reference and clinical strains were detected, respectively. H. pylori colonies were isolated from gastric specimens taken from both the antrum and the fundus in 68 (90.66%) of 75 urea breath test (UBT)-positive patients. Moreover, GESA transport medium allowed the recovery and isolation of H. pylori colonies from additional biopsy samples from 13 of the 75 detected subjects at up to 10 days of biopsy sample storage at 4 °C. Finally, GESA transport medium preserved its characteristics when stored at 4°C for 1 year from its preparation, thus allowing good recovery of H. pylori. GESA transport medium can be considered a standardized transport medium with high performance that optimizes the recovery rate of H. pylori grown by culture.

  16. Biofilm and Helicobacter pylori: From environment to human host

    PubMed Central

    García, Apolinaria; Salas-Jara, María José; Herrera, Carolina; González, Carlos

    2014-01-01

    Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively colonizes the human gastric epithelium. Over 50% of the world population is infected with H. pylori reaching up to 90% of infected individuals in developing countries. Nonetheless the increased impact upon public health care, its reservoir and the transmission pathway of the species has not been clearly established yet. Molecular studies allowed the detection of H. pylori in various aquatic environments, even forming biofilm in tap water distribution systems in several countries, suggesting a role of water as a possible reservoir of the pathogen. The persistence of human infection with H. pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the last years, experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents. However, only two anti- H. pylori biofilm disrupting agents have been successfully used: Curcumin - a natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory diseases. The main goal of this review was to discuss the evidences available in the literature supporting the ability of H. pylori to form biofilm upon various surfaces in aquatic environments, both in vivo and in vitro. The results published and our own observations suggest that the ability of H. pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans, mainly through natural water sources and water distribution systems. PMID:24914322

  17. Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors

    PubMed Central

    Al-Marhoon, Mohammed S.; Ouhtit, Allal; Al-Abri, Aisha O.; Venkiteswaran, Krishna P.; Al-Busaidi, Qassim; Mathew, Josephkunju; Al-Haddabi, Ibrahim; Shareef, Omar; Aquil, Shahid; Rahman, Khalid; Al-Hashmi, Intisar; Gupta, Ishita; Ganguly, Shyam S.

    2015-01-01

    Objectives To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa. Methods One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables. Results Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09–23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients. Conclusions This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa. PMID:26889133

  18. Helicobacter Pylory infection in patients with esophageal squamous cell carcinoma

    PubMed Central

    Poyrazoglu, Omer Bilgehan; Dulger, Ahmet Cumhur; Gultepe, Bilge Sumbul

    2017-01-01

    OBJECTIVE: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy. METHOD: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively. RESULTS: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively). CONCLUSION: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy. PMID:28355360

  19. Transforming growth factor-beta/Smads signaling induces transcription of the cell type-restricted ankyrin repeat protein CARP gene through CAGA motif in vascular smooth muscle cells.

    PubMed

    Kanai, H; Tanaka, T; Aihara, Y; Takeda, S; Kawabata, M; Miyazono, K; Nagai, R; Kurabayashi, M

    2001-01-19

    Transforming growth factor (TGF)-beta plays a major role in the development of vascular diseases. Despite the pleiotropic effects of TGF-ss on vascular smooth muscle cells (VSMCs), only a few genes have been characterized as direct targets of TGF-beta in VSMCs. Cardiac ankyrin repeat protein (CARP) has been thought to be expressed exclusively in the heart. In the present study, we showed that CARP is expressed in the vasculature after balloon injury and in cultured VSMCs in response to TGF-beta. Analysis of a half-life of the cytoplasmic CARP mRNA levels and the transient transfection of the CARP promoter/luciferase gene indicates that the regulation of CARP expression is increased by TGF-beta at the transcriptional level. Transfection of expression vectors encoding Smads significantly activated the CARP promoter/luciferase activity. Deletion analysis and site-specific mutagenesis of the CARP promoter indicate that TGF-beta response element is localized to CAGA motif at -108 bp relative to the transcription start site. Electrophoretic mobility shift assays showed that the binding activity to the CAGA motif was increased in nuclear extracts of cultured VSMCs by TGF-beta. Cells transfected with adenovirus vector expressing CARP showed a significant decrease in DNA synthesis. Overexpression of CARP enhanced the TGF-beta-mediated inhibition of the DNA synthesis. These data indicate that CARP is a downstream target of TGF-beta/Smad signaling in VSMCs and suggest a role of CARP in mediation of the inhibitory effects of TGF-beta on the proliferation of VSMCs.

  20. A 20-minute breath test for helicobacter pylori

    SciTech Connect

    Marshall, B.J.; Plankey, M.W.; Hoffman, S.R.; Boyd, C.L.; Dye, K.R.; Frierson, H.F. Jr.; Guerrant, R.L.; McCallum, R.W. )

    1991-04-01

    In this study, we evaluated a simplified rapid {sup 14}C-urea breath test for the diagnosis of Helicobacter pylori. Fasting patients undergoing initial assessment for H. pylori drank 5 microCi of {sup 14}C-urea in 20 ml of water. Breath was collected at intervals for 30 min. Samples were counted in a beta-counter, and the results were expressed as counts per minute (cpm). In the same week, patients underwent endoscopy, and a blinded investigator examined biopsy samples of gastric mucosa by culture and histology for H. pylori. There were 49 H. pylori-negative (HP-) and 104 H. pylori-positive (HP+) patients in the study. HP+ patients expired a mean of 4398 cpm (SD 2468) per mmol CO{sub 2} in a sample taken 20 min after ingestion of the isotope. In contrast, HP--patients expired only 340 cpm (SD 196). If the mean +3 SD of HP- patients was used as a cutoff value, the 20-minute sample gave a sensitivity of 97% and a specificity of 100% for detecting H. pylori. The radiation exposure from this test is less than 1% of that received from an upper gastrointestinal series, and the short collection time makes it both convenient and cost effective.

  1. Lymphocytic gastritis and Helicobacter pylori infection in gastric lymphoma.

    PubMed Central

    Miettinen, A; Karttunen, T J; Alavaikko, M

    1995-01-01

    Lymphocytic gastritis and primary gastric lymphoma are rare conditions with unknown aetiology. It has recently been suggested that Helicobacter pylori has a role in the pathogenesis of both of them. The occurrence of lymphocytic gastritis and H pylori was studied in a series of patients with primary gastric lymphoma. The cases of primary gastric lymphomas (n = 35) diagnosed in years 1970-1993 were identified. The specimens of 22 cases contained gastric mucosa sufficiently so that the number of intra-epithelial lymphocytes, severity of gastritis, and occurrence of H pylori could be studied. Lymphocytic gastritis was detected in seven of 22 patients (32%), and in most cases both in antral and body mucosa. Atrophy of the body glands was significantly more severe in lymphocytic gastritis patients. H pylori was detected in 13 of all 22 patients (59%); two of seven lymphocytic gastritis patients (29%), and 11 of 15 (73%) of patients without lymphocytic gastritis were H pylori positive. Patients with gastric lymphoma have significantly increased prevalence of lymphocytic gastritis. Rarity of H pylori in these patients might be connected with atrophic changes in body mucosa. Further studies are needed to show the significance of lymphocytic gastritis as a precursor of gastric lymphoma. Images Figure 2 Figure 3 Figure 4 PMID:7489930

  2. The Relationship between H. pylori Infection and Osteoporosis in Japan.

    PubMed

    Asaoka, Daisuke; Nagahara, Akihito; Hojo, Mariko; Sasaki, Hitoshi; Shimada, Yuji; Yoshizawa, Takashi; Osada, Taro; Watanabe, Sumio

    2014-01-01

    Background and Objective. H. pylori infection causes a chronic inflammation in the gastric mucosa. However, this local inflammation may result in extra-digestive conditions. Our aim is to investigate the relationship between H. pylori infection and osteoporosis in Japan. Methods. This cross-sectional study was conducted among outpatients at the Juntendo University Hospital between 2008 and 2014. Participants for patient profile, H. pylori infection status, comorbidity, internal medical therapies, lumbar dual-energy X-ray absorptiometry (DXA), and bone turnover marker were collected and upper gastrointestinal endoscopy for reflux esophagitis, hiatal hernia, peptic ulcer disease (PUD), and endoscopic gastric mucosal atrophy (EGA) was performed. The diagnosis of osteoporosis was performed in accordance with the Japanese criteria. We investigated risk factors of osteoporosis. Results. Of the eligible 200 study subjects, 41 cases were of osteoporosis. Bivariate analysis showed that age, being female, BMI, alcohol, smoking, H. pylori, bone-specific ALP, PUD, and EGA were related to osteoporosis. Multivariate analysis showed that age (OR 1.13; 95%CI 1.07-1.20), being female (OR 4.77; 95%CI 1.78-12.77), BMI (OR 0.79; 95%CI 0.68-0.92), H. pylori (OR 5.33; 95%CI 1.73-16.42), and PUD (OR 4.98; 95%CI 1.51-16.45) were related to osteoporosis. Conclusions. H. pylori infection may be a risk factor of osteoporosis in Japan.

  3. Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy

    PubMed Central

    Liao, Wei-Chih; Huang, Mei-Zi; Wang, Michelle Lily; Lin, Chun-Jung; Lu, Tzu-Li; Lo, Horng-Ren; Pan, Yi-Jiun; Sun, Yu-Chen; Kao, Min-Chuan; Lim, Hui-Jing; Lai, Chih-Ho

    2017-01-01

    Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been found to provide protective effects against several bacterial infectious diseases. Although the use of statins has been shown to enhance antimicrobial treated Helicobacter pylori eradication and reduce H. pylori-mediated inflammation, the mechanisms underlying these effects remain unclear. In this study, in vitro and ex vivo macrophage models were established to investigate the molecular pathways involved in statin-mediated inhibition of H. pylori-induced inflammation. Our study showed that statin treatment resulted in a dose-dependent decrease in intracellular H. pylori burden in both RAW264.7 macrophage cells and murine peritoneal exudate macrophages (PEMs). Furthermore, statin yielded enhanced early endosome maturation and subsequent activation of the autophagy pathway, which promotes lysosomal fusion resulting in degradation of sequestered bacteria, and in turn attenuates interleukin (IL)-1β production. These results indicate that statin not only reduces cellular cholesterol but also decreases the H. pylori burden in macrophages by promoting autophagy, consequently alleviating H. pylori-induced inflammation. PMID:28144585

  4. Genome Sequencing Reveals a Phage in Helicobacter pylori

    PubMed Central

    Lehours, Philippe; Vale, Filipa F.; Bjursell, Magnus K.; Melefors, Ojar; Advani, Reza; Glavas, Steve; Guegueniat, Julia; Gontier, Etienne; Lacomme, Sabrina; Alves Matos, António; Menard, Armelle; Mégraud, Francis; Engstrand, Lars; Andersson, Anders F.

    2011-01-01

    ABSTRACT Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, likely to grow as more genomes are sampled. Here we describe the draft genome sequence (63 contigs; 26× mean coverage) of H. pylori strain B45, isolated from a patient with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The major finding was a 24.6-kb prophage integrated in the bacterial genome. The prophage shares most of its genes (22/27) with prophage region II of Helicobacter acinonychis strain Sheeba. After UV treatment of liquid cultures, circular DNA carrying the prophage integrase gene could be detected, and intracellular tailed phage-like particles were observed in H. pylori cells by transmission electron microscopy, indicating that phage production can be induced from the prophage. PCR amplification and sequencing of the integrase gene from 341 H. pylori strains from different geographic regions revealed a high prevalence of the prophage (21.4%). Phylogenetic reconstruction showed four distinct clusters in the integrase gene, three of which tended to be specific for geographic regions. Our study implies that phages may play important roles in the ecology and evolution of H. pylori. PMID:22086490

  5. Diagnosis of Helicobacter pylori infection by invasive and noninvasive tests.

    PubMed

    Pourakbari, Babak; Ghazi, Mona; Mahmoudi, Shima; Mamishi, Setareh; Azhdarkosh, Hossein; Najafi, Mehri; Kazemi, Bahram; Salavati, Ali; Mirsalehian, Akbar

    2013-01-01

    Although several invasive and noninvasive tests have been developed for the diagnosis of Helicobacter pylori infection, all of the tests have their limitations. We conducted a study to investigate and compare the suitability of rapid urease test (RUT), serology, histopathology and stool antigen tests with polymerase chain reaction (PCR) for detection of H. pylori, and correlate the diagnostic methods with PCR. Eighty nine patients (61 adults, 28 children) referred to the Firoozgar Hospital and Children Medical Center Hospital for diagnostic upper gastrointestinal endoscopy entered to the study and noninvasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in feces were measured. The biopsies were utilized for histological examination, RUT and PCR. The H. pylori statuses were evaluated by the positivity of ureC PCR in biopsy specimens and 53 subjects had H. pylori positive result. Histopathology showed high overall performance in adults and children with sensitivity and specificity 100% and 90%, respectively. Sensitivity, specificity, and accuracy for stool antigen test were 87.8%, 75% and 82%, respectively. Correlation of RUT, serology (IgG), histopathology and stool antigen tests with PCR were 0.82, 0.32, 0.91 and 0.63, respectively. In conclusion, the RUT and histopathology are as accurate as the PCR of biopsy and stool antigen test can consider as appropriate noninvasive test for detection of H. pylori infection.

  6. [Helicobacter pylori gastritis: assessment of OLGA and OLGIM staging systems].

    PubMed

    Ben Slama, Sana; Ben Ghachem, Dorra; Dhaoui, Amen; Jomni, Mohamed Taieb; Dougui, Mohamed Hédi; Bellil, Khadija

    2016-01-01

    Helicobacter pylori (H pylori) gastritis presents a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to identify high-risk forms (stages III and IV). The aim of this study is to evaluate the OLGA and OLGIM staging systems in H pylori gastritis. A descriptive study of 100 cases of chronic H pylori gastritis was performed. The revaluation of Sydney System parameters of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed identifying respectively the stages of OLGA and OLGIM systems. The progressive risk of our H pylori gastritis was 6% according to OLGA staging and 7% according to OLGIM staging. Significant correlation was revealed between age and OLGA staging. High-risk gastritis according to OLGIM staging was significantly associated with moderate to severe atrophy. High-risk forms according to OLGA staging were associated in 80% of the cases to intestinal metaplasia. OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 5% for H pylori gastritis. The OLGA and OLGIM staging systems in addition to Sydney System, allow selection of high risk forms of chronic gastritis requiring accurate observation.

  7. Methods for Detecting the Environmental Coccoid Form of Helicobacter pylori

    PubMed Central

    Mazaheri Assadi, Mahnaz; Chamanrokh, Parastoo; Whitehouse, Chris A.; Huq, Anwar

    2015-01-01

    Helicobacter pylori is recognized as the most common pathogen to cause gastritis, peptic and duodenal ulcers, and gastric cancer. The organisms are found in two forms: (1) spiral-shaped bacillus and (2) coccoid. H. pylori coccoid form, generally found in the environment, is the transformed form of the normal spiral-shaped bacillus after exposed to water or adverse environmental conditions such as exposure to sub-inhibitory concentrations of antimicrobial agents. The putative infectious capability and the viability of H. pylori under environmental conditions are controversial. This disagreement is partially due to the fact of lack in detecting the coccoid form of H. pylori in the environment. Accurate and effective detection methods of H. pylori will lead to rapid treatment and disinfection, and less human health damages and reduction in health care costs. In this review, we provide a brief introduction to H. pylori environmental coccoid forms, their transmission, and detection methods. We further discuss the use of these detection methods including their accuracy and efficiency. PMID:26075197

  8. Growth phase-dependent composition of the Helicobacter pylori exoproteome.

    PubMed

    Snider, Christina A; Voss, Bradley J; McDonald, W Hayes; Cover, Timothy L

    2016-01-01

    Helicobacter pylori colonizes the human stomach and is associated with an increased risk of gastric cancer and peptic ulcer disease. Analysis of H. pylori protein secretion is complicated by the occurrence of bacterial autolysis. In this study, we analyzed the exoproteome of H. pylori at multiple phases of bacterial growth and identified 74 proteins that are selectively released into the extracellular space. These include proteins known to cause alterations in host cells, antigenic proteins, and additional proteins that have not yet been studied in any detail. The composition of the H. pylori exoproteome is dependent on the phase of bacterial growth. For example, the proportional abundance of the vacuolating toxin VacA in culture supernatant is higher during late growth phases than early growth phases, whereas the proportional abundance of many other proteins is higher during early growth phases. We detected marked variation in the subcellular localization of putative secreted proteins within soluble and membrane fractions derived from intact bacteria. By providing a comprehensive view of the H. pylori exoproteome, these results provide new insights into the array of secreted H. pylori proteins that may cause alterations in the gastric environment.

  9. [The diagnostic of chronic infection Helicobacter pylori in children].

    PubMed

    Tereschenko, S Yu; Olkhovskiy, I A

    2014-02-01

    The epidemiological studies testify an extremely high prevalence of chronic infection of children with Helicobacter pylori in Russia. The affection consists from 50% to 80% depending on region and age of examined children. The currently in force recommendations "Maastricht IV" concerning diagnostic and treatment of Helicobacter pylori infection adult patients are applied not in its fullness to children adolescent population. At the same time recently published joint conciliatory document of the European and North American associations of pediatric gastroenterologists is oriented to populations with low prevalence of Helicobacter pylori infection and particular profile of drug resistance. Hence, an urgent need exists to develop modern local algorithm concerning diagnostic, treatment and control of eradication of Helicobacter pylori infection among children and adolescents in Russia. The review presents analysis of admissibility of application in Russia's conditions of the international conciliatory documents concerning diagnostic of Helicobacter pylori infection in children. The data from conciliatory document of the European (ESPGHAN) and North American (NASPGHAN) associations of pediatric gastroenterologists, particular orginal research studies and one's own clinical experience were used. The advantages and shortcomings of actual methods of laboratory diagnostic of Helicobacter pylori infection are discussed. The approaches to application of particular diagnostic methods are considered. The enhanced indications to detection of infection and implementation of eradication therapy are proposed.

  10. Antibiotic treatment for Helicobacter pylori: Is the end coming?

    PubMed Central

    Kim, Su Young; Choi, Duck Joo; Chung, Jun-Won

    2015-01-01

    Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID:26558152

  11. Helicobacter pylori infection in India from a western perspective.

    PubMed

    Thirumurthi, Selvi; Graham, David Y

    2012-10-01

    Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of medical research and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here we discuss H. pylori as a problem in India with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments are discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

  12. Helicobacter pylori infection in India from a western perspective.

    PubMed

    Thirumurthi, Selvi; Graham, David Y

    2010-09-01

    Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of Medicine and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here, we discuss H. pylori as an Indian problem with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments is discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

  13. Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

    PubMed Central

    Graham, David Y.

    2015-01-01

    Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections. PMID:25655557

  14. Helicobacter pylori and autoimmune disease: Cause or bystander

    PubMed Central

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  15. Transmission of Helicobacter pylori: a role for food?

    PubMed Central

    van Duynhoven, Y. T.; de Jonge, R.

    2001-01-01

    Helicobacter pylori colonizes and grows in human gastric epithelial tissue and mucus. Its presence is associated with gastritis and there is substantial evidence that it causes peptic and duodenal ulcers and chronic gastritis. Since 1994, H. pylori has been classified as carcinogenic to humans. In industrialized countries, as many as 50% of adults are infected with the pathogen, while in the developing world, prevalence values of about 90% have been reported. As little is known about the mode of transmission, a literature search was carried out to determine whether food acts a reservoir or vehicle in the transmission of H. pylori. Although growth of the pathogen should be possible in the gastrointestinal tract of all warm-blooded animals, the human stomach is its only known reservoir. Under conditions where growth is not possible, H. pylori can enter a viable, but nonculturable state. H. pylori has been detected in such states in water, but not in food. Person-to-person contact is thought to be the most likely mode of transmission, and there is no direct evidence that food is involved in the transmission of H. pylori. PMID:11417041

  16. Diagnosis of Helicobacter pylori infection: Current options and developments

    PubMed Central

    Wang, Yao-Kuang; Kuo, Fu-Chen; Liu, Chung-Jung; Wu, Meng-Chieh; Shih, Hsiang-Yao; Wang, Sophie SW; Wu, Jeng-Yih; Kuo, Chao-Hung; Huang, Yao-Kang; Wu, Deng-Chyang

    2015-01-01

    Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes. PMID:26523098

  17. Analysis of Helicobacter pylori Prevalence in Chittagong, Bangladesh, Based on PCR and CLO Test

    PubMed Central

    Habib, Abdul Musaweer; Alam, Md. Jibran; Rudra, Bashudev; Quader, Md. Abdul; Al-Forkan, Mohammad

    2016-01-01

    The pathogenic bacterium Helicobacter pylori is a causative agent of gastric diseases in Bangladesh as well as throughout the world. This study aimed at analyzing the prevalence of H. pylori infection among dyspeptic patients in Chittagong, the second most populous city of Bangladesh, using 16S rRNA-based H. pylori-specific Polymerase Chain Reaction and Campylobacter-like organism test. We found that 67% of the population under study was positive for H. pylori infection. Gastric ulcer and duodenal ulcer disease showed statistically significant association with H. pylori infection; however, no association of H. pylori infection was observed in terms of age and gender. This study would play a crucial role in managing H. pylori-induced gastric diseases by understanding the current trend of H. pylori infection in the Chittagong region of Bangladesh. PMID:27891051

  18. Helicobacter pylori in gastroduodenal diseases: rapid identification by endoscopic brush cytology.

    PubMed

    De Francesco, F; Nicòtina, P A; Picciotto, M; Martines, F; Ferlazzo, G; d'Aquino, A

    1993-08-01

    Previous reports showed Helicobacter pylori (H. pylori) in type B gastritis-affected stomachs. This study was carried out to compare H. pylori staining effectiveness on biopsy to brush cytology. Tissue and brush parallel samples of gastric mucosa with abnormal or normal appearances were examined: 57.6% H. pylori-positive pieces from the antrum and 19.2% from the body were found, versus 65.3% and 25% H. pylori-positive brush smears, respectively. H. pylori resembling organisms were mainly related to chronic and acute antral inflammations and were often associated with higher amounts of round-shaped cocco-bacteria. In addition, H. pylori direct stain on brushing is proposed as the most rapid and reliable method for the routine diagnosis of Helicobacter pylori infection, in both ulcer or nonulcer gastritis.

  19. [Expanded indication of National Health Insurance for H. pylori associated gastritis].

    PubMed

    Kato, Mototsugu

    2014-05-01

    Since National Health Insurance covered eradication therapy for H. pylori infected gastritis, all patients with H. pylori infection could be received eradication under insurance. Cure of H. pylori infection improves histological gastritis, also atrophic change, and intestinal metaplasia. Prevention of H. pylori associated diseases such as gastric cancer is expected. According to Insurance instruction, it is carried out in order of endoscopic diagnosis of chronic gastritis, diagnosis of H. pylori infection, and eradication treatment. Endoscopic examination prior to H. pylori diagnosis is necessary for screening of gastric cancer. Endoscopic finding of RAC (regular arrangement of collecting venules) in the angle of stomach suggests lack of infection with H. pylori, disappearance of RAC suspects H. pylori infection.

  20. p53, a potential predictor of Helicobacter pylori infection-associated gastric carcinogenesis?

    PubMed Central

    Lu, Nong-Hua

    2016-01-01

    Helicobacter pylori (H. pylori) is an ancient and persistent inhabitant of the human stomach that is closely linked to the development of gastric cancer (GC). . Emerging evidence suggests that H. pylori strain interactions with gastric epithelial cells subvert the best- characterized p53 tumour suppressor pathway. A high prevalence of p53 mutations is related to H. pylori infection. H. pylori also accelerates p53 protein degradation by disturbing the MDM2-P53 feedback loop. Additionally, H. pylori triggers the alteration of other p53 isoforms. Dysregulation of p53 by H. pylori infection contributes to gastric carcinogenesis by mediating cell proliferation and apoptosis. This review focuses on the regulation of p53 in H. pylori infection-associated GC. PMID:27556187

  1. Helicobacter pylori FliD protein is a highly sensitive and specific marker for serologic diagnosis of H. pylori infection.

    PubMed

    Khalifeh Gholi, Mohammad; Kalali, Behnam; Formichella, Luca; Göttner, Gereon; Shamsipour, Fereshteh; Zarnani, Amir Hassan; Hosseini, Mostafa; Busch, Dirk H; Shirazi, Mohammad Hasan; Gerhard, Markus

    2013-12-01

    Screening for H. pylori in large populations continues to be a challenging task, since available tests have limited sensitivity and specificity, which, in population-based approaches, leads to significant numbers of false positive and false negative results. Various H. pylori proteins associated with virulence are highly immunogenic and therefore candidates to detect the infection. There are currently no defined markers that are recognized in all H. pylori infected patients and that do not show cross-reactivity with other bacterial proteins. We identified the H. pylori "hook-associated protein 2 homologue", FliD (UniProtKB/Swiss-Prot: P96786.4) as a novel marker of infection for serological analysis. The H. pylori FliD protein is an essential element in the assembly of the functional flagella. However, this virulence factor has not yet been tested as a diagnostic marker in serology. For this purpose FliD was recombinantly expressed in E. coli, purified by affinity chromatography and gel filtration and used to coat ELISA plates or immobilized on nitrocellulose stripes. To evaluate its antigenicity we screened a defined panel of patient sera. The recombinant H. pylori FliD protein reacted with a high percentage of human sera. Among 318 samples reported positive by histology, 310 (97.4%) were tested positive by FliD Line assay, and 165 out of 170 samples were tested positive by ELISA (97%). We could also reconfirm 297 out of 300 (99%) negative sera by Line assay and 73 from 76 (96%) by ELISA. Taken together, application of FliD in serological diagnosis of H. pylori infection presents a high specificity of up to 99% and a sensitivity of up to 97%. This makes especially the FliD ELISA a simple, cost effective and highly efficient tool to detect H. pylori infection in developing countries where prevalence is high and other screening methods are either not available or are unaffordable.

  2. Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.

    PubMed Central

    1997-01-01

    There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin. PMID:9274464

  3. Antibodies Anti-Caga Cross-React with Trophoblast Cells: A Risk Factor for Pre-Eclampsia?

    PubMed Central

    Franceschi, Francesco; Di Simone, Nicoletta; D’Ippolito, Silvia; Castellani, Roberta; Di Nicuolo, Fiorella; Gasbarrini, Giovanni; Yamaoka, Yoshio; Todros, Tullia; Scambia, Giovanni; Gasbarrini, Antonio

    2013-01-01

    Background Previous studies reported an epidemiological association between CagA-positive H. pylori strains and pre-eclampsia. As antibodies anti-CagA cross-react with endothelial cells and trophoblast cells show an endothelial phenotypic profile, we hypothesized that anti-CagA antibodies may recognize antigens of cytotrophoblast cells, thus impairing their function. Materials and Methods Placenta samples were obtained from healthy women. Cytotrophoblast cells were cultured in a medium containing increasing concentration of polyclonal anti-CagA antibodies. Binding of anti-CagA antibodies to cytotrophoblast cells was evaluated by cell ELISA and immunofluorescence assay. Invasive potential of those cells was assessed by an invasion culture system and by measuring of MMP-2. Protein sequencing was performed on antigens precipitated by anti-CagA antibodies. Measurement of phosphorylated ERK expression and NF-kB DNA-binding activity in trophoblast cells incubated with anti-CagA or irrelevant antibodies was also performed. Results Anti-CagA antibodies recognized β-actin of cytotrophoblast cells, showing a dose-dependent binding. Incubation of cytotrophoblast cells with increasing doses of anti-CagA antibodies significantly reduced their invasiveness and determined a significant decrease in phosphorylated ERK expression and a reduced NF-kB translocation activity. Conclusions This study shows that anti-CagA antibodies recognize β-actin of cytotrophoblast cells, reducing their invasiveness ability, possibly giving a biological explanation for the epidemiological association. PMID:23066738

  4. CONVENTIONAL VIDEOENDOSCOPY CAN IDENTIFY HELICOBACTER PYLORI GASTRITIS?

    PubMed Central

    GOMES, Alexandre; SKARE, Thelma Larocca; PRESTES, Manoel Alberto; COSTA, Maiza da Silva; Petisco, Roberta Dombroski; RAMOS, Gabriela Piovezani

    2016-01-01

    ABSTRACT Background: Studies with latest technologies such as endoscopy with magnification and chromoendoscopy showed that various endoscopic aspects are clearly related to infection by Helicobacter pylori (HP). The description of different patterns of erythema in gastric body under magnification of images revived interest in identifying these patterns by standard endoscopy. Aim: To validate the morphologic features of gastric mucosa related to H. pylori infection gastritis allowing predictability of their diagnosis as well as proper targeting biopsies. Methods: Prospective study of 339 consecutive patients with the standard videoendoscope image analysis were obtained, recorded and stored in a program database. These images were studied with respect to the presence or absence of H. pylori, diagnosed by rapid urease test and/or by histological analysis. Were studied: a) normal mucosa appearance; b) mucosal nodularity; c) diffuse nonspecific erythema or redness (with or without edema of folds and exudate) of antrum and body; d) mosaic pattern with focal area of hyperemia; e) erythema in streaks or bands (red streak); f) elevated (raised) erosion; g) flat erosions; h) fundic gland polyps. The main exclusion criteria were the use of drugs, HP pre-treatment and other entities that could affect results. Results: Applying the exclusion criteria, were included 170 of the 339 patients, of which 52 (30.58%) were positive for HP and 118 negative. On the positive findings, the most associated with infection were: nodularity in the antrum (26.92%); presence of raised erosion (15.38%) and mosaic mucosa in the body (21.15%). On the negative group the normal appearance of the mucosa was 66.94%; erythema in streaks or bands in 9.32%; flat erosions 11.86%; and fundic gland polyps 11.86%. Conclusion: Endoscopic findings are useful in the predictability of the result and in directing biopsies. The most representative form of HP related gastritis was the nodularity of the antral mucosa

  5. Effects of prolonged chlorine exposures upon PCR detection of Helicobacter pylori DNA.

    EPA Science Inventory

    The effect of low doses of free chlorine on the detection by qPCR of Helicobacter pylori (H. pylori) cells by qPCR in tap water was monitored. H. pylori target sequences (within suspended, intact cells at densities of 102 to 103 cells /ml) were rendered undetectable by qPCR an...

  6. "Helicobacter Pylori" Infection in Five Inpatient Units for People with Intellectual Disability and Psychiatric Disorder

    ERIC Educational Resources Information Center

    Clarke, David; Vemuri, Murali; Gunatilake, Deepthi; Tewari, Sidhartha

    2008-01-01

    Background: A high prevalence of "Helicobacter pylori" infection has been reported among people with intellectual disability, especially those residing in hospital and similar settings. Surveys of inpatients have found unusually high rates of gastrointestinal malignancy, to which "H. pylori" infection predisposes. Methods: "Helicobacter pylori"…

  7. Streptococcus mitis Induces Conversion of Helicobacter pylori to Coccoid Cells during Co-Culture In Vitro

    PubMed Central

    Khosravi, Yalda; Dieye, Yakhya; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna

    2014-01-01

    Helicobacter pylori (H. pylori) is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptocccus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes. PMID:25386948

  8. Helicobacter pylori and food products: a public health problem.

    PubMed

    Herrera, Anavella Gaitan

    2004-01-01

    Helicobacter pylori is a major human pathogen causing gastritis and chronic superficial infection (CSG). It colonizes the stomach of more than 50% of humans and causes disease. This microorganism is associated with the gastric antral epithelium in patients with active chronic gastritis, peptic (gastric) or duodenal ulcers, and gastric adenocarcinoma H. pylori is present in feces, sewage, and water but is killed by routine chlorination. Therefore, in developing countries, consumption of sewage-contaminated drinking water and vegetables may pose a risk; properly cooking foods and chlorinating water reduces the risk of transmitting H. pylori to humans. In South America the consumption of raw vegetables fertilized with human feces has been found to be a risk factor for infection, and consumption of water from a municipal supply has been suggested as a risk factor for children. Epidemiological studies have found that H. pylori organisms colonize the stomach and duodenum of humans and many animal species and family clusters; it is believed to be orally transmitted person to person. This transmission is the major, if not exclusive, source of infection.H. pylori has been detected in the mouth from dental plaque. Recent observations in persons infected with H. pylori caused to vomit or have diarrhea showed that an actively unwell person with these symptoms could spread H. pylori in the immediate vicinity by aerosol, splashing of vomitus, infected vomitus, and infected diarrhea. In summary, H. pylori is usually spread by the fecal-oral route but possibly also by the oral-oral route and the spread of contaminated secretions. Thus, in developing countries, individuals catch H. pylori at a very young age from other persons (children) in their environment. In developed countries, H. pylori is more difficult to acquire and is usually transmitted from one family member to another, possibly by the fecal-oral route, or by the oral-oral route, e.g., kissing, vomitus. On occasion

  9. Helicobacter pylori-negative Russell body gastritis: Case report

    PubMed Central

    Gobbo, Alessandro Del; Elli, Luca; Braidotti, Paola; Nuovo, Franca Di; Bosari, Silvano; Romagnoli, Solange

    2011-01-01

    Russell body gastritis is an unusual form of chronic gastritis characterized by the permeation of lamina propria by numerous plasma cells with eosinophilic cytoplasmic inclusions. Very few cases have been reported in the literature; the majority of which have shown Helicobacter Pylori (H. pylori) infection, thus suggesting a correlation between plasma cell presence and antigenic stimulation by H. pylori. We present a case of Russell body gastritis in a 78-year-old woman who was undergoing esophagogastroduodenoscopy for epigastric pain. Gastric biopsy of the gastroesophageal junction showed the presence of cells with periodic acid-Schiff-positive hyaline pink bodies. Giemsa staining for H. pylori infection was negative, as well as immunohistochemical detection. The cells with eosinophilic inclusions stained positive for CD138, CD79a, and κ and lambda light chains, which confirmed plasma cell origin. In particular, κ and lambda light chains showed a polyclonal origin and the patient was negative for immunological dyscrasia. The histological observations were confirmed by ultrastructural examination. The cases reported in the literature associated with H. pylori infection have shown regression of plasma cells after eradication of H. pylori. Nothing is known about the progression of H. pylori-negative cases. The unusual morphological appearance of this type of chronic gastritis should not be misinterpreted during routine examination, and it should be distinguished from other common forms of chronic gastritis. It is mandatory to exclude neoplastic diseases such as gastric carcinoma, lymphoma and plasmocytoma by immunohistochemistry and electron microscopy, which can help with differential diagnosis. The long-term effects of plasma cells hyperactivation are still unknown, because cases of gastric tumor that originated in patients affected by Russell body gastritis have not been described in the literature. We are of the opinion that these patients should be scheduled

  10. Helicobacter pylori-negative Russell body gastritis: case report.

    PubMed

    Del Gobbo, Alessandro; Elli, Luca; Braidotti, Paola; Di Nuovo, Franca; Bosari, Silvano; Romagnoli, Solange

    2011-03-07

    Russell body gastritis is an unusual form of chronic gastritis characterized by the permeation of lamina propria by numerous plasma cells with eosinophilic cytoplasmic inclusions. Very few cases have been reported in the literature; the majority of which have shown Helicobacter Pylori (H. pylori) infection, thus suggesting a correlation between plasma cell presence and antigenic stimulation by H. pylori. We present a case of Russell body gastritis in a 78-year-old woman who was undergoing esophagogastroduodenoscopy for epigastric pain. Gastric biopsy of the gastroesophageal junction showed the presence of cells with periodic acid-Schiff-positive hyaline pink bodies. Giemsa staining for H. pylori infection was negative, as well as immunohistochemical detection. The cells with eosinophilic inclusions stained positive for CD138, CD79a, and κ and lambda light chains, which confirmed plasma cell origin. In particular, κ and lambda light chains showed a polyclonal origin and the patient was negative for immunological dyscrasia. The histological observations were confirmed by ultrastructural examination. The cases reported in the literature associated with H. pylori infection have shown regression of plasma cells after eradication of H. pylori. Nothing is known about the progression of H. pylori-negative cases. The unusual morphological appearance of this type of chronic gastritis should not be misinterpreted during routine examination, and it should be distinguished from other common forms of chronic gastritis. It is mandatory to exclude neoplastic diseases such as gastric carcinoma, lymphoma and plasmocytoma by immunohistochemistry and electron microscopy, which can help with differential diagnosis. The long-term effects of plasma cells hyperactivation are still unknown, because cases of gastric tumor that originated in patients affected by Russell body gastritis have not been described in the literature. We are of the opinion that these patients should be scheduled

  11. Probiotics in Helicobacter pylori-induced peptic ulcer disease.

    PubMed

    Boltin, Doron

    2016-02-01

    The ideal treatment regimen for the eradication Helicobacter pylori infection has yet to be identified. Probiotics, particularly Lactobacillus, Bifidobacterium and Saccharomyces, have been suggested as adjuncts to antibiotics for the treatment of H. pylori. There is in vitro evidence that probiotics dampen the Th1 response triggered by H. pylori, attenuate H. pylori associated hypochlorhydria and secrete bacteriocidal metabolites. Probiotics interact with the innate host immune system through adherence to the gastric epithelium and secretion of bacterial adhesins. In prospective human studies, probiotic monotherapy effectively decrease H. pylori density (expired (13)CO2) by 2.0%-64.0%. Probiotic monotherapy has also been shown to eradicate H. pylori in up to 32.5%, although subsequent recrudescence is likely. Eleven meta-analyses have evaluated the efficacy of probiotics as adjuvants to antibiotics for the eradication of H. pylori. The addition of a probiotic increased treatment efficacy, OR 1.12-2.07. This benefit is probably strain-specific and may only be significant with relatively ineffective antibiotic regimens. The pooled prevalence of adverse effects was 12.9%-31.5% among subjects receiving adjuvant probiotics, compared with 24.3%-45.9% among controls. Diarrhea in particular was significantly reduced in subjects receiving adjuvant probiotics, compared with controls (OR 0.16-0.47). A reduction in adverse events other than diarrhea is variable. Despite the apparent benefit on efficacy and side effects conferred by probiotics, the optimal probiotic species, dose and treatment duration has yet to be determined. Further studies are needed to identify the probiotic, antibiotic and patient factors which might predict benefit from probiotic supplementation.

  12. [Could Helicobacter pylori treatment reduce stomach cancer risk?].

    PubMed

    Bretagne, Jean-François

    2003-03-01

    Despite its dramatic decline in incidence in developed countries, gastric cancer is a major public health issue in the world. Accumulating evidence for considering H. pylori as a causal factor for gastric cancer comes from recent epidemiologic studies, the advent of an animal model of gastric cancer and from new insights into the biological mechanisms for gastric carcinogenesis. The stomach cancer risk for people infected with H. pylori is rather low, inferior to 1%. It depends on genotypic polymorphisms of both the bacterium and the host. Environmental risk factors such as smoking habits, salt intake, and the amount of antioxidants in diet may interfere with H. pylori and modify the cancer risk. There is no definite clinical evidence of the benefit of eradication on cancer risk in humans due to the lack of randomized controlled studies in large populations. The occurrence of gastric adenocarcinomas in patients after complete remission of gastric MALT lymphoma induced by H. pylori eradication suggests also the limits of the preventive strategy against gastric cancer. Furthermore, the effectiveness of eradication to reverse precancerous gastric lesions such as severe atrophy and intestinal metaplasia is questionable. For many reasons discussed in our review, population-based screening and routine eradication of H. pylori infection seem to be an unrealistic goal and cannot be recommended in France. By waiting for effective anti-H. pylori vaccine, public health measures such as dietary modification should be promoted to further decrease the gastric cancer incidence. On the individual basis the specialist has a role in the diagnosis of gastric precancerous lesions by endoscopy and also in the prevention of gastric cancer by selecting indications for H. pylori therapy.

  13. Overview of the phytomedicine approaches against Helicobacter pylori

    PubMed Central

    Vale, Filipa F; Oleastro, Mónica

    2014-01-01

    Helicobacter pylori (H. pylori) successfully colonizes the human stomach of the majority of the human population. This infection always causes chronic gastritis, but may evolve to serious outcomes, such as peptic ulcer, gastric carcinoma or mucosa-associated lymphoid tissue lymphoma. H. pylori first line therapy recommended by the Maastricht-4 Consensus Report comprises the use of two antibiotics and a proton-pomp inhibitor, but in some regions failure associated with this treatment is already undesirable high. Indeed, treatment failure is one of the major problems associated with H. pylori infection and is mainly associated with bacterial antibiotic resistance. In order to counteract this situation, some effort has been allocated during the last years in the investigation of therapeutic alternatives beyond antibiotics. These include vaccines, probiotics, photodynamic inactivation and phage therapy, which are briefly revisited in this review. A particular focus on phytomedicine, also described as herbal therapy and botanical therapy, which consists in the use of plant extracts for medicinal purposes, is specifically addressed, namely considering its history, category of performed studies, tested compounds, active principle and mode of action. The herbs already experienced are highly diverse and usually selected from products with a long history of employment against diseases associated with H. pylori infection from each country own folk medicine. The studies demonstrated that many phytomedicine products have an anti-H. pylori activity and gastroprotective action. Although the mechanism of action is far from being completely understood, current knowledge correlates the beneficial action of herbs with inhibition of essential H. pylori enzymes, modulation of the host immune system and with attenuation of inflammation. PMID:24914319

  14. The Role of Helicobacter pylori in Laryngopharyngeal Reflux.

    PubMed

    Campbell, Ross; Kilty, Shaun J; Hutton, Brian; Bonaparte, James P

    2017-02-01

    Objective The primary objective was to determine the prevalence of Helicobacter pylori among patients with laryngopharyngeal reflux. The secondary objective was determining if H pylori eradication leads to greater symptom improvement in patients with laryngopharyngeal reflux as compared with standard proton pump inhibitor therapy alone. Data Sources EMBASE, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, World Health Organization International Clinical Trials Registry Platform, European Union Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov. Review Methods A systematic review was performed of studies assessing the diagnosis or treatment of H pylori among patients with laryngopharyngeal reflux. Randomized controlled trials, cohort studies, case-control studies, and case series were included. A meta-analysis of prevalence data and assessment of heterogeneity was performed on relevant studies. Results Fourteen studies were analyzed in the review, with 13 eligible for the meta-analysis. We determined that the prevalence of H pylori among patients with laryngopharyngeal reflux was 43.9% (95% confidence interval, 32.1-56.5). The heterogeneity of studies was high, with an overall I(2) value of 92.3%. We were unable to quantitatively assess findings for our secondary outcome, since H pylori identification and treatment were not the primary focus of the majority of studies. Conclusion There is a high rate of H pylori infection among patients with laryngopharyngeal reflux. The infection rate in North America and Western Europe has not been adequately studied. There is insufficient evidence to make a recommendation regarding the testing and treatment of H pylori infection among patients with laryngopharyngeal reflux.

  15. [Diagnosis and treatment guidelines for Helicobacter pylori infection in Korea].

    PubMed

    Kim, Nayoung; Kim, Jae J; Choe, Yon Ho; Kim, Hyun Soo; Kim, Jin Il; Chung, In-Sik

    2009-11-01

    Eleven years has passed since the guideline of the Korean College of Helicobacter and Upper Gastrointestinal Research group for H. pylori infection was produced in 1998. During this period the research for H. pylori has much progressed that H. pylori is now regarded as the major cause of gastric cancer. The seroprevalence of H. pylori in Korea was found to be decreased especially below the age of 40s and in the area of Seoul-Gyeonggi province, and annual reinfection rate of H. pylori has decreased up to 2.94%. In the aspect of diagnostic tests of H. pylori the biopsy is recommended in the body instead of antrum in the subjects with atrophic gastritis and/or intestinal metaplasia for the modified Giemsa staining or Warthin Starry silver staining. The urea breath test is the test of choice to confirm eradication when follow-up endoscopy is not necessary. Definite indication for H. pylori eradication is early gastric cancer in addition to the previous indications of peptic ulcer including scar and Marginal zone B cell lymphoma (MALT type). Treatment is also recommended for the relatives of gastric cancer patient, unexplained iron deficiency anemia, and chronic idiopathic thrombocytopenic purpura. One or two week treatment of proton pump inhibitor (PPI) based triple therapy consisting of one PPI and two antibiotics, clarithromycin and amoxicillin, is recommended as the first line treatment regimen. In the case of treatment failure, one or two weeks of quadruple therapy (PPI+metronidazole+tetracycline+bismuth) is recommended. Herein, Korean College of Helicobacter and Upper Gastrointestinal Research proposes a diagnostic and treatment guideline based on currently available evidence.

  16. The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer.

    PubMed

    Moss, Steven F

    2017-03-01

    Gastric cancer has long been recognized to be accompanied and preceded by chronic gastritis, lasting decades. Arguably, the most important development in our understanding of gastric cancer pathogenesis over the past 50 years has been the realization that, for most cases of gastric cancer, Helicobacter pylori is the cause of the underlying gastritis. Gastritis can promote gastric carcinogenesis, typically via the Correa cascade of atrophic gastritis, intestinal metaplasia, and dysplasia. Nested case-control studies have shown that H pylori infection increases the risk of gastric cancer significantly, both of the intestinal and diffuse subtypes, and that H pylori is responsible for approximately 90% of the world's burden of noncardia gastric cancer. Based largely on randomized studies in high gastric cancer prevalence regions in East Asia, it appears that primary and tertiary intervention to eradicate H pylori can halve the risk of gastric cancer. Some public health authorities now are starting screening and treatment programs to reduce the burden of gastric cancer in these high-risk areas. However, there is currently much less enthusiasm for initiating similar attempts in the United States. This is partially because gastric cancer is a relatively less frequent cause of cancer in the United States, and in addition there are concerns about theoretical downsides of H pylori eradication, principally because of the consistent inverse relationship noted between H pylori and esophageal adenocarcinoma. Nevertheless, establishing a link between chronic H pylori infection and gastric cancer has led to novel insights into cancer biology, the gastrointestinal microbiome, and on individual and population-based gastric cancer prevention strategies.

  17. Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes.

    PubMed

    Ito, Takashi; Kobayashi, Daisuke; Uchida, Keisuke; Takemura, Tamiko; Nagaoka, Sakae; Kobayashi, Intetsu; Yokoyama, Tetsuji; Ishige, Ikuo; Ishige, Yuki; Ishida, Noriko; Furukawa, Asuka; Muraoka, Hiroe; Ikeda, Satoshi; Sekine, Masaki; Ando, Noboru; Suzuki, Yoshimi; Yamada, Tetsuo; Suzuki, Takashige; Eishi, Yoshinobu

    2008-06-01

    Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.

  18. The Role of PPARγ in Helicobacter pylori Infection and Gastric Carcinogenesis

    PubMed Central

    Lee, Jong-Min; Kim, Sung Soo; Cho, Young-Seok

    2012-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγ plays an important role in gastric mucosal injury due to Helicobacter pylori (H. pylori). As H. pylori infection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγ in H. pylori infection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγ in H. pylori infection and its related gastric carcinogenesis. PMID:22936949

  19. [Kyoto global consensus report for treatment of Helicobacter pylori and its implications for China].

    PubMed

    Xie, Chuan; Lyu, Nonghua

    2016-01-01

    Kyoto global consensus report on Helicobacter pylori gastritis (Gut, July 2015) is another important international consensus since the European Maastricht Ⅳ consensus was published. Kyoto consensus will improve the etiology-based classification, the diagnostic assessment of gastritis, and the treatment of H. pylori-associated dyspepsia and H. pylori gastritis. However, because of high rate of H. pylori infection and antibiotic resistance as well as limited health resources in China, we need to develop our own strategies of H. pylori infection control with the reference of the Kyoto global consensus.

  20. Prevalence of Helicobacter pylori Infection in Samples of Gastric Biopsies

    PubMed Central

    Trindade, Leda Maria Delmondes Freitas; Menezes, Lania Barreto de Oliveira; de Souza Neta, Adozina Marques; Leite Rolemberg, Paulo Candido; Souza, Lais Dantas; Barreto, Ikaro Daniel de Carvalho; Meurer, Luise

    2017-01-01

    Background Helicobacter pylori (H. pylori) infection affects about 50% of the world population and its association with environmental factors and host properties is involved in gastric carcinogenesis. The study aimed to estimate the prevalence of H. pylori in samples of gastric mucosa biopsies, correlate the presence of the bacteria in the sample with the variables age, sex and origin, to identify the types of lesions found in patients with H. pylori, and to evaluate the association of the lesions with the region of the gastric mucosa. Methods A cross-sectional, retrospective study was carried out in Aracaju, Sergipe, Brazil, from January 2013 to December 2015. A total of 45,206 gastric mucosal biopsies were obtained from patients submitted to upper gastrointestinal endoscopy. Of the reports evaluated, 12,909 met the inclusion criteria since they presented the patient’s demographic data as well as the histopathological characteristics of gastric mucosal regions and positivity for H. pylori. Data were analyzed by IBM SPSS Statistic 20 and subjected to descriptive analyses (categorical variables) and inferential (Pearson’s Qui-square and linear association tests) and multiple correspondence analyses. Significance level adopted 5%. Results Of the total of 12,909 (28.6%) reports evaluated, 67% (8,647) came from urban areas and 64.5% (8,320) were female. The mean age (standard deviation (SD)) was 43 years, ranging from 8 to 100 years, prevailing between 21 and 60 years. Among the types of gastric mucosa analyzed, 95.5% (12,322) were of the antral mucosa. The absence of glandular atrophy, the mild infection intensity for H. pylori, the absence of metaplasia, the presence of foveolar hyperplasia and lymphoid follicles were statistically significant (P < 0.001) in this region. In the fundic region, the evidence of fibrinoleucocytic crust and lymphoid follicles was significant (P < 0.001). There was no evidence of associated ulcerated lesions or significant relationship

  1. The Antibacterial Activity of Honey on Helicobacter Pylori

    PubMed Central

    Nzeako, Basil C; Al-Namaani, Faiza

    2006-01-01

    Objective: This project aimed to assess the antibacterial potential of various brands of honey sold in Muscat area on some isolates of H. pylori and to determine if there is any synergy between honey and amoxycillin or clarithromycin used in the treatment of H. pylori gastritis and duodenal ulcer. Methods: Eight samples of commercial honey were used in the experiment after they were checked for purity by sub-culturing on blood agar and incubating for 48 hours at 37°c. Honey samples showing gross contamination were discarded. Purified culture isolates of H. pylori from our laboratory stock cultures were swabbed on chocolate plate using 1x 104 cfu/ml. One hundred microlitres (100μl) of various honey samples were placed on each plate which was subsequently incubated microaerophilically at 37ºc for 3 days. The presence or absence of growth inhibition zones on each plate was noted and an average zone size of each honey was taken. Honey samples with high zone sizes were further diluted from 1:2–1:8 to find the end-points of their growth inhibition concentrations and the experiment was repeated in triplicates. The synergistic effect between honey, amoxycillin and clarithromycin was done in triplicates by placing honey at various distances between each antibiotic after swabbing chocolate agar with 1x 104 cfu/ml of H. pylori. The plates were incubated as before. Results: All honey samples produced growth inhibition zones with H. pylori no at dilution of honey but had different zone sizes at 1:2–1:8 dilutions. Black Forest honey had the highest antibacterial activity followed by Langnese honey. None of the honeys had a synergistic effect with either clarithromycin or amoxycillin. Conclusion: We conclude that, in vitro, some honey brands possess antibacterial activity against H. pylori and that no synergy or antagonism was observed between honey and clarithromycin or honey and amoxicillin using H. pylori as a test organism. Though no synergy or antagonism was observed

  2. Drug therapy for Helicobacter pylori infection: problems and pitfalls.

    PubMed

    Glupczynski, Y; Burette, A

    1990-12-01

    Antibacterial chemotherapy against Helicobacter pylori is currently being assessed by open or randomized controlled clinical studies for its efficacy in eradicating this bacterium from the stomach of patients with gastritis or gastroduodenal ulcer. Whereas there is presently no "optimal" agent and treatment scheme, the combination of some antibiotics (metronidazole, tinidazole, amoxicillin) with bismuth salts proves definitely superior in vivo to either of these agents administered alone. Several reasons have been proposed, to explain the clinical failure after treatment: insufficient concentration of active drugs in gastric mucus, instability of some agents at an acidic pH, inappropriate formulation of drug, insufficient duration of treatment, and variable compliance of patients. Recently, it has appeared from several clinical trials that H. pylori may rapidly acquire resistance to some antibiotics, and that this event might also account for clinical failure. A critical review of the literature on H. pylori treatment indicates that association of bismuth and antibiotics or of antibiotics alone both may efficiently reduce the risk of emergence of resistance and improve the therapeutic outcome. Guidelines of treatment are suggested in order to avoid the future misuse of antibiotics that would increase selection of antibiotic-resistant H. pylori and negatively affect the ecology of the gastric microflora. Likewise, an accurate definition of a subset of patients with H. pylori who really will require treatment needs to be rapidly established.

  3. Quinolone-containing therapies in the eradication of Helicobacter pylori.

    PubMed

    Chuah, Seng-Kee; Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

    2014-01-01

    Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to "rescue" therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

  4. Does Helicobacter pylori exhibit corkscrew motion while swimming?

    NASA Astrophysics Data System (ADS)

    Constantino, Maira; Hardcastle, Joseph; Bansil, Rama

    2015-03-01

    Helicobacter pylori is a spiral shaped bacterium associated with ulcers, gastric cancer, gastritis among other diseases. In order to colonize the harsh acidic environment of the stomach H. pylori has to go across the viscoelastic mucus layer of the stomach. Many studies have been conducted on the swimming of H. pylori in viscous media however none have taken into account the influence of cell-body shape on the trajectory. We present an experimental study of the effects of body shape in the swimming trajectory of H. pylori in viscous media by a quantitative analysis of the bacterium rotation and translation in gels using phase contrast microscopy and particle tracking techniques. Preliminary microscopic tracking measurements show very well defined helical trajectories in the spiral-shaped wild type H. pylori. These helical trajectories are not seen in rod-shaped mutants which sometimes display whirling motion about one end acting as a hinge. We will present an analysis of the different trajectories for bacteria swimming in media with different viscoelastic parameters. Supported by the National Science Foundation PHY PoLS.

  5. Chinese Helicobacter pylori vaccine: Solution for an old challenge?

    PubMed Central

    Talebi Bezmin Abadi, Amin; Lee, Yeong Yeh

    2016-01-01

    Helicobacter pylori (H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world’s population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class I carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase III study of an oral recombinant vaccine (Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children (6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge. PMID:27602242

  6. PCR Detection of Helicobacter pylori in Clinical Samples

    PubMed Central

    Rimbara, Emiko; Sasatsu, Masanori; Graham, David Y.

    2014-01-01

    Helicobacter pylori is an important pathogen whose primary niche is the human stomach. H. pylori is etio-logically associated with gastric inflammation (gastritis), peptic ulcer disease, and gastric cancer. Both noninvasive (e.g., urea breath and stool antigen tests) and invasive (gastric biopsy for histology, culture, or PCR) tests are used for diagnosis. PCR detection of H. pylori has been reported using a variety of clinical samples including gastric biopsy, gastric juice, saliva, dental plaque, and stools as well as environmental samples. Whenever possibly, noninvasive tests are preferred over invasive tests. H. pylori are excreted in the stool. Culture from stool is variable whereas stool antigen testing is widely used. Stool consists of a complicated mixture of commensal bacteria and chemicals and often includes inhibitors of PCR. Nevertheless, simple extraction methods are available to efficiently extract DNA from human stools and nested-PCR targeting the 23S rRNA gene have proven to be highly sensitive for the detection of H. pylori. Detection of clarithromycin susceptibility/resistance is important clinically and the mutation of the 23S rRNA gene responsible for resistance can also be detected using stool. This described method can be modified for other clinical samples such as gastric juice or biopsy material. PMID:23104297

  7. Review of Helicobacter pylori infection and chronic renal failure.

    PubMed

    Sugimoto, Mitsushige; Yamaoka, Yoshio

    2011-02-01

    Chronic renal failure patients receiving hemodialysis and continuous ambulatory peritoneal dialysis often encounter gastrointestinal troubles over their long treatment period. Helicobacter pylori infection has close association with development of peptic ulcer, gastric cancer and gastric lymphoma, and is thought to be one of the major risk factors for gastrointestinal troubles in dialysis patients. However, it is unclear whether H. pylori infection is directly associated with progression of renal dysfunction and prognosis of chronic renal failure patients. Recent consensus shows that the prevalence of H. pylori infection in chronic renal failure patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in hemodialysis patients, the prevalence of infection decreases as dialysis periods progressed, in particular within the first four years after the start of treatment. However, the chance of natural eradication becomes rare for patients receiving dialysis treatment for a long time. Moreover, chronic renal failure patients with H. pylori infection have a higher incidence of gastroduodenal diseases, and therefore, are recommended to receive eradication therapies, especially for those receiving treatment for a long time and with higher risks of complication. Intensive endoscopic check-ups for the prevention of gastrointestinal events and the discovery of peptic ulcer and neoplastic diseases at an early phase may be required.

  8. Role of gastritis pattern on Helicobacter pylori eradication.

    PubMed

    Zullo, Angelo; Severi, Carola; Vannella, Lucy; Hassan, Cesare; Sbrozzi-Vanni, Andrea; Annibale, Bruno

    2012-12-01

    Helicobacter pylori eradication rate following standard triple therapy is decreasing. Identification of predictive factors of therapy success would be useful for H. pylori management in clinical practice. This study aimed to evaluate the role of different gastritis patterns on the efficacy of the currently suggested 14-day triple therapy regimen. One-hundred and seventeen, consecutive, non-ulcer dyspeptic patients, with H. pylori infection diagnosed at endoscopy, were enrolled. All patients received a 14-day, triple therapy with lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g, all given twice daily. Bacterial eradication was assessed with (13)C-urea breath test 4-6 weeks after completion of therapy. H. pylori infection was cured in 70.1% at ITT analysis and 83.7% at PP analysis. The eradication rate tended to be lower in patients with corpus-predominant gastritis as compared to those with antral-predominant gastritis at both ITT (66.1 vs 74.5%) and PP (80.4 vs 87.2%) analyses. The multivariate analysis failed to identify factors associated with therapy success. However, 14-day triple therapy does not achieve acceptable H. pylori cure rate in Italy, and should be not recommended in clinical practice.

  9. Contemporary Diagnostic Strategies for the Detection of Helicobacter pylori Infection

    PubMed Central

    Elfant, Adam B.; Howden, Colin W.; Stollman, Neil

    2012-01-01

    Helicobacter pylori infection is highly prevalent, affecting approximately half of the world’s population. While the majority of infected individuals are asymptomatic, H. pylori infection is associated with certain diseases, including peptic ulcers (either duodenal or gastric), gastritis, and 2 malignancies—gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. Many of the epidemiologic associations between these diseases and H. pylori infection have been further validated by treatment studies, which show that effective eradication therapy correlates with a decreased risk of disease. A variety of testing strategies are used to detect H. pylori infection. Serologic techniques are widely available and inexpensive, but they are no longer preferred as they have low sensitivities and specificities, and they may show a positive result for a long period following effective therapy. The remaining testing methods are divided into 2 categories: invasive tests (which require endoscopy) and noninvasive tests. Noninvasive test methods such as the urea breath test and stool antigen test have gained popularity due to their high sensitivities and specificities. Further, both of these methods may be used to confirm the absence of infection following eradication therapy. Due to the increasing incidence of treatment failure (caused in part by antibiotic resistance), post-treatment testing is recommended to confirm H. pylori eradication. PMID:24847180

  10. Analysis of Helicobacter pylori genotypes in clinical gastric wash samples.

    PubMed

    Miyamoto, Shuichi; Watanabe, Yoshiyuki; Oikawa, Ritsuko; Ono, Shoko; Mabe, Katsuhiro; Kudo, Takahiko; Yamamoto, Hiroyuki; Itoh, Fumio; Kato, Mototsugu; Sakamoto, Naoya

    2016-08-01

    Helicobacter pylori is a key factor in the development of gastric cancer; indeed, clearance of H. pylori helps prevent gastric cancer. However, the relationship between gastric cancer and the abundance and diversity of H. pylori genotypes in the stomach remains unknown. Here, we present, for the first time, a quantitative analysis of H. pylori genotypes in gastric washes. A method was first developed to assess diversity and abundance by pyrosequencing and analysis of single nucleotide polymorphisms in 23S ribosomal RNA (rRNA), a gene associated with clarithromycin resistance. This method was then validated using arbitrarily mixed plasmids carrying 23S rRNA with single nucleotide polymorphisms. Multiple strains were detected in many of 34 clinical samples, with frequency 24.3 ± 24.2 and 26.3 ± 33.8 % for the A2143G and A2144G strains, respectively. Importantly, results obtained from gastric washes were similar to those obtained from biopsy samples. The method provides opportunities to investigate drug resistance in H. pylori and assess potential biomarkers of gastric cancer risk, and should thus be validated in large-scale clinical trials.

  11. [Animal models for the study of Helicobacter pylori infection].

    PubMed

    Miszczyk, Eliza; Walencka, Maria; Mikołajczyk-Chmiela, Magdalena

    2014-05-15

    The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural history of H. pylori infection. Preclinical investigations on animal models are an essential stage of research which enrich the knowledge on treatment and prevention strategies.

  12. Helicobacter pylori Stores Nickel To Aid Its Host Colonization

    PubMed Central

    Benoit, Stéphane L.; Miller, Erica F.

    2013-01-01

    The transition metal nickel (Ni) is critical for the pathogenicity of Helicobacter pylori. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important for in vivo colonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellular H. pylori protein content, and therefore the bacterial Ni demand is very high. H. pylori possess two small and abundant histidine-rich, Ni-binding proteins, Hpn and Hpn-like, whose physiological role in the host have not been investigated. In this study, special husbandry conditions were used to control Ni levels in the host (mouse), including the use of Ni-free versus Ni-supplemented food. The efficacy of each diet was confirmed by measuring the Ni concentrations in sera of mice fed with either diet. Colonization levels (based on rank tests) of the Δhpn Δhpn-like double mutants isolated from the mice provided Ni-deficient chow were statistically lower than those for mice given Ni in their diet. In contrast, H. pylori wild-type colonization levels were similar in both host groups (e.g., regardless of Ni levels). Our results indicate that the gastric pathogen H. pylori can utilize stored Ni via defined histidine-rich proteins to aid colonization of the host. PMID:23230291

  13. Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection

    PubMed Central

    Lee, Sun-Young

    2016-01-01

    Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer. PMID:27604795

  14. Antimicrobial activity of Northwestern Mexican plants against Helicobacter pylori.

    PubMed

    Robles-Zepeda, Ramón E; Velázquez-Contreras, Carlos A; Garibay-Escobar, Adriana; Gálvez-Ruiz, Juan C; Ruiz-Bustos, Eduardo

    2011-10-01

    Helicobacter pylori is the major etiologic agent of such gastric disorders as chronic active gastritis and gastric carcinoma. Over the past few years, the appearance of antibiotic-resistant bacteria has led to the development of better treatments, such as the use of natural products. This study evaluated the anti-H. pylori activity of 17 Mexican plants used mainly in the northwestern part of Mexico (Sonora) for the empirical treatment of gastrointestinal disorders. The anti-H. pylori activity of methanolic extracts of the plants was determined by using the broth microdilution method. The 50% minimum inhibitory concentrations ranged from less than 200 to 400 μg/mL for Castella tortuosa, Amphipterygium adstringens, Ibervillea sonorae, Pscalium decompositum, Krameria erecta, Selaginella lepidophylla, Pimpinella anisum, Marrubium vulgare, Ambrosia confertiflora, and Couterea latiflora and were greater than 800 μg/mL for Byophyllum pinnatum, Tecoma stans linnaeus, Kohleria deppena, Jatropha cuneata, Chenopodium ambrosoides, and Taxodium macronatum. Only Equisetum gigantum showed no activity against H. pylori. This study suggests the important role that these plants may have in the treatment of gastrointestinal disorders caused by H. pylori. The findings set the groundwork for further characterization and elucidation of the active compounds responsible for such activity.

  15. Identification of Helicobacter pylori genes that contribute to stomach colonization.

    PubMed

    Baldwin, David N; Shepherd, Benjamin; Kraemer, Petra; Hall, Michael K; Sycuro, Laura K; Pinto-Santini, Delia M; Salama, Nina R

    2007-02-01

    Chronic infection of the human stomach by Helicobacter pylori leads to a variety of pathological sequelae, including peptic ulcer and gastric cancer, resulting in significant human morbidity and mortality. Several genes have been implicated in disease related to H. pylori infection, including the vacuolating cytotoxin and the cag pathogenicity island. Other factors important for the establishment and maintenance of infection include urease enzyme production, motility, iron uptake, and stress response. We utilized a C57BL/6 mouse infection model to query a collection of 2,400 transposon mutants in two different bacterial strain backgrounds for H. pylori genetic loci contributing to colonization of the stomach. Microarray-based tracking of transposon mutants allowed us to monitor the behavior of transposon insertions in 758 different gene loci. Of the loci measured, 223 (29%) had a predicted colonization defect. These included previously described H. pylori virulence genes, genes implicated in virulence in other pathogenic bacteria, and 81 hypothetical proteins. We have retested 10 previously uncharacterized candidate colonization gene loci by making independent null alleles and have confirmed their colonization phenotypes by using competition experiments and by determining the dose required for 50% infection. Of the genetic loci retested, 60% have strain-specific colonization defects, while 40% have phenotypes in both strain backgrounds for infection, highlighting the profound effect of H. pylori strain variation on the pathogenic potential of this organism.

  16. Helicobacter pylori infection--a boon or a bane: lessons from studies in a low-prevalence population.

    PubMed

    Lee, Yeong Yeh; Mahendra Raj, Sundramoorthy; Graham, David Y

    2013-10-01

    Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori-infected non-Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.

  17. Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model.

    PubMed Central

    Kabir, A M; Aiba, Y; Takagi, A; Kamiya, S; Miwa, T; Koga, Y

    1997-01-01

    BACKGROUND: Helicobacter pylori is a bacterium which causes gastric inflammatory diseases. Oral inoculation of H pylori usually results in only a temporary colonisation without a successful infection in the stomach of conventional mice in which lactobacilli are the predominant indigenous bacteria. AIM: To determine whether lactobacilli exert an inhibitory effect on colonisation by H pylori in the stomach. METHODS: The effects of H pylori on attachment to murine and human gastric epithelial cells and the H pylori mediated release of interleukin-8 (IL-8) by these cells were examined in vitro. Lactobacillus salivarius infected gnotobiotic BALB/c mice and control germ free mice were inoculated orally with H pylori to examine whether L salivarius can inhibit colonisation by H pylori. RESULTS: L salivarius inhibited both the attachment and IL-8 release in vitro. H pylori could not colonise the stomach of L salivarius infected gnotobiotic BALB/c mice, but colonised in large numbers and subsequently caused active gastritis in germ free mice. In addition, L salivarius given after H pylori implantation could eliminate colonisation by H pylori. CONCLUSION: These findings suggest the possibility of lactobacilli being used as probiotic agents against H pylori. Images PMID:9274471

  18. Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms.

    PubMed

    Inoue, Izumi; Kato, Jun; Tamai, Hideyuki; Iguchi, Mikitaka; Maekita, Takao; Yoshimura, Noriko; Ichinose, Masao

    2014-02-14

    To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.

  19. Antimicrobial Characterization of Inula britannica against Helicobacter pylori on Gastric Condition.

    PubMed

    Lee, Young Hwan; Lee, Na-Kyoung; Paik, Hyun-Dong

    2016-06-28

    The antimicrobial effects of methanol and ethanol extracts of Inula britannica against several Helicobacter pylori strains (26695, J99, and SS1) were evaluated in vitro, to determine their applicability as functional foods. In the paper disc diffusion method, the antimicrobial effects of the I. britannica extracts against the H. pylori strains were apparent. Viable cell counting also showed that the extracts at 100 μg/ml concentration dramatically decreased the viability of the H. pylori strains. In particular, the methanol and ethanol extracts at a concentration of 100 μg/ml reduced the H. pylori SS1 cell number to 2.46 log CFU/ml and 1.08 log CFU/ml, respectively. In the presence of 100 μg/ml extracts, the urease production of H. pylori SS1 was decreased to more than 30%, whereas that of H. pylori J99 and H. pylori 26695 was decreased to about 20%, relative to the controls. The extracts inhibited the attachment of the H. pylori strains to human gastric AGS cells as well as caused the detachment of already attached H. pylori cells. In addition, the H. pylori morphology was changed to a coccoidal shape in the presence of the extracts. In conclusion, the I. britannica extracts were effective against H. pylori strains in vitro, irrespective of genotype status, and could therefore be used as novel functional foods.

  20. Cost-Effectiveness Analysis of Helicobacter pylori Diagnostic Methods in Patients with Atrophic Gastritis

    PubMed Central

    Shimbo, Takuro; Ohde, Sachiko; Fukui, Tsuguya

    2017-01-01

    Background. There are several diagnostic methods for Helicobacter pylori (H. pylori) infection. A cost-effective analysis is needed to decide on the optimal diagnostic method. The aim of this study was to determine a cost-effective diagnostic method in patients with atrophic gastritis (AG). Methods. A decision-analysis model including seven diagnostic methods was constructed for patients with AG diagnosed by esophagogastroduodenoscopy. Expected values of cost and effectiveness were calculated for each test. Results. If the prevalence of H. pylori in the patients with AG is 85% and CAM-resistant H. pylori is 30%, histology, stool H. pylori antigen (SHPAg), bacterial culture (BC), and urine H. pylori antibody (UHPAb) were dominated by serum H. pylori IgG antibody (SHPAb), rapid urease test (RUT), and urea breath test (UBT). Among three undominated methods, the incremental cost-effective ratios (ICER) of RUT versus SHPAb and UBT versus RUT were $214 and $1914, respectively. If the prevalence of CAM-sensitive H. pylori was less than 55%, BC was not dominated, but its H. pylori eradication success rate was 0.86. Conclusions. RUT was the most cost-effective at the current prevalence of CAM-resistant H. pylori. BC could not be selected due to its poor effectiveness even if CAM-resistant H. pylori was more than 45%. PMID:28337217

  1. Structural characterization of purine nucleoside phosphorylase from human pathogen Helicobacter pylori.

    PubMed

    Štefanić, Zoran; Mikleušević, Goran; Luić, Marija; Bzowska, Agnieszka; Ašler, Ivana Leščić

    2017-03-20

    Microaerophilic bacterium Helicobacer pylori is a well known human pathogen involved in the development of many diseases. Due to the evergrowing infection rate and increase of H. pylori antibiotic resistence, it is of utmost importance to find a new way to attack and eradicate H. pylori. The purine metabolism in H. pylori is solely dependant on the salvage pathway and one of the key enzymes in this pathway is purine nucleoside phosphorylase (PNP). In this timely context, we report here the basic biochemical and structural characterization of recombinant PNP from the H. pylori clinical isolate expressed in Escherichia coli. Structure of H. pylori PNP is typical for high molecular mass PNPs. However, its activity towards adenosine is very low, thus resembling more that of low molecular mass PNPs. Understanding the molecular mechanism of this key enzyme may lead to the development of new drug strategies and help in the eradication of H. pylori.

  2. Helicobacter pylori infection and extragastric disorders in children: a critical update.

    PubMed

    Pacifico, Lucia; Osborn, John F; Tromba, Valeria; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-02-14

    Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in the last decades, abetted by modern clinical practices, may have other health consequences.

  3. Helicobacter pylori infection and extragastric disorders in children: A critical update

    PubMed Central

    Pacifico, Lucia; Osborn, John F; Tromba, Valeria; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-01-01

    Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in the last decades, abetted by modern clinical practices, may have other health consequences. PMID:24587617

  4. Screening test for anti-Helicobacter pylori activity of traditional Chinese herbal medicines

    PubMed Central

    Ma, Feng; Chen, Ye; Li, Jing; Qing, He-Ping; Wang, Ji-De; Zhang, Ya-Li; Long, Bei-Guo; Bai, Yang

    2010-01-01

    AIM: To evaluate the anti-Helicobacter pylori (H. pylori) activity of 50 traditional Chinese herbal medicines in order to provide the primary evidence for their use in clinical practice. METHODS: A susceptibility test of water extract from 50 selected traditional Chinese herbal medicines for in vitro H. pylori Sydney strain 1 was performed with broth dilution method. Anti-H. pylori activity of the selected Chinese herbal medicines was evaluated according to their minimum inhibitory concentration (MIC). RESULTS: The water extract from Rhizoma Coptidis, Radix Scutellariae and Radix isatidis could significantly inhibit the H. pylori activity with their MIC less than 7.8 mg/mL, suggesting that traditional Chinese herbal medicines have anti-inflammatory and antibacterial effects and can thus be used in treatment of H. pylori infection. CONCLUSION: Rhizoma Coptidis, Radix Scutellariae and Radix isatidis are the potential sources for the synthesis of new drugs against H. pylori. PMID:21105198

  5. An association between Helicobacter pylori and upper respiratory tract disease: Fact or fiction?

    PubMed Central

    Kariya, Shin; Okano, Mitsuhiro; Nishizaki, Kazunori

    2014-01-01

    Helicobacter pylori (H. pylori) is a major cause of chronic gastritis and gastric ulcers and considerable evidence supports the notion that infection with this bacterium is also associated with gastric malignancy in addition to various other conditions including pulmonary, vascular and autoimmune disorders. Gastric juice infected with H. pylori might play an important role in upper respiratory tract infection. Although direct and/or indirect mechanisms might be involved in the association between H. pylori and upper respiratory tract diseases, the etiological role of H. pylori in upper respiratory tract disorders has not yet been fully elucidated. Although various studies over the past two decades have suggested a relationship between H. pylori and upper respiratory tract diseases, the findings are inconsistent. The present overview describes the outcomes of recent investigations into the impact of H. pylori on upper respiratory tract and adjacent lesions. PMID:24587622

  6. Expression of Melatonin Synthesizing Enzymes in Helicobacter pylori Infected Gastric Mucosa

    PubMed Central

    Chojnacki, Cezary; Popławski, Tomasz; Reiter, Russel J.; Klupinska, Grazyna

    2013-01-01

    Helicobacter pylori colonization of gastric mucosa causes pain of unknown etiology in about 15–20% of infected subjects. The aim of the present work was to determine the level of expression of enzymes involved in the synthesis of melatonin in gastric mucosa of asymptomatic and symptomatic H. pylori infected patients. To diagnose H. pylori infection, histological analysis and the urea breath test (UBT C13) were performed. The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AA-NAT) and acetylserotonin methyltransferase (ASMT) were estimated in gastric mucosa with RT-PCR. The level of AA-NAT expression and AMST was decreased in H. pylori infected patients and was increased after H. pylori eradication. We conclude that decreased expression of melatonin synthesizing enzymes, AA-NAT and ASMT, in patients with symptomatic H. pylori infection returns to normal level after H. pylori eradication. PMID:23936850

  7. Association between Helicobacter pylori and end-stage renal disease: A meta-analysis

    PubMed Central

    Wijarnpreecha, Karn; Thongprayoon, Charat; Nissaisorakarn, Pitchaphon; Lekuthai, Natasorn; Jaruvongvanich, Veeravich; Nakkala, Kiran; Rajapakse, Ridhmi; Cheungpasitporn, Wisit

    2017-01-01

    AIM To investigate the prevalence and association of Helicobacter pylori (H. pylori) with end-stage renal disease (ESRD). METHODS SA comprehensive literature search was completed from inception until October 2016. Studies that reported prevalence, relative risks, odd ratios, hazard ratios or standardized incidence ratio of H. pylori among ESRD patients were included. Participants without H. pylori were used as comparators to assess the association between H. pylori infection and ESRD. Pooled risk ratios and 95%CI was calculated using a random-effect model. Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird. RESULTS Of 4546 relevant studies, thirty-seven observational studies met all inclusion criteria. Thirty-five cross-sectional studies were included in the analyses to assess the prevalence and association of H. pylori with ESRD. The estimated prevalence of H. pylori among ESRD patients was 44% (95%CI: 40%-49%). The pooled RR of H. pylori in patients with ESRD was 0.77 (95%CI: 0.59-1.00) when compared with the patients without ESRD. Subgroup analysis showed significantly reduced risk of H. pylori in adult ESRD patients with pooled RR of 0.71 (95%CI: 0.55-0.94). The data on the risk of ESRD in patients with H. pylori were limited. Two cohort studies were included to assess the risk of ESRD in patients with H. pylori. The pooled risk RR of ESRD in patients with H. pylori was 0.61 (95%CI: 0.03-12.20). CONCLUSION The estimated prevalence of H. pylori in ESRD patients is 44%. Our meta-analysis demonstrates a decreased risk of H. pylori in adult ESRD patients. PMID:28293097

  8. Comparative Genomics of H. pylori and Non-Pylori Helicobacter Species to Identify New Regions Associated with Its Pathogenicity and Adaptability

    PubMed Central

    Lu, Qun-Feng; Li, Song-Bo; Wang, Ju-Ping; Chen, Yu-Li

    2016-01-01

    The genus Helicobacter is a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species. Helicobacter pylori (H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings of H. pylori that are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representative H. pylori and 24 non-pylori Helicobacter genomes. There were 1173 conserved protein families of H. pylori and 673 of all 99 Helicobacter genus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of the H. pylori but lacked in non-pylori Helicobacter species. The operons, genes, and sRNAs within the H. pylori unique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship. PMID:28078297

  9. Suppression of Helicobacter pylori urease activity by sucralfate and sulglycotide.

    PubMed

    Slomiany, B L; Piotrowski, J; Slomiany, A

    1997-06-01

    The effect of gastroprotective agents, sucralfate and sulglycotide, on the in vitro activity of H. pylori urease was investigated. The bacterium was subjected to sonication, centrifuged, and the supernatant used as an enzyme source. The assays revealed that the rate of urea degradation was proportional to enzyme protein up to 100 micrograms and remained constant with time for 10 min. Introduction of sucralfate or sulglycotide to the assay system led to the reduction in the rate of ammonia production. With both drugs the optimal inhibition was attained at 10 micrograms/ml, at which dose a 63.1% decrease in urease activity occurred with sucralfate and a 70.2% inhibition was obtained with sulglycotide. The findings demonstrate that the inhibitory action of sucralfate and sulglycotide on H. pylori urease activity may be of value in the treatment of gastric disease associated with H. pylori infection.

  10. Anti-Helicobacter pylori xanthones of Garcinia fusca.

    PubMed

    Nontakham, Jannarin; Charoenram, Napaporn; Upamai, Wanchalerm; Taweechotipatr, Malai; Suksamrarn, Sunit

    2014-08-01

    A new geranylated xanthone derivative, fuscaxanthone I (1), along with nine xanthones (2-9 and 11), a biphenyl (10) and three biflavonoids (12-14) were isolated from the roots of Garcinia fusca Pierre. Compounds 8, 10 and 11-14 were reported from this plant species for the first time. Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR and MS. The isolated compounds were evaluated for antibacterial activity against Helicobacter pylori. Cowaxanthone (5) and fukugiside (14) exhibited stronger inhibitory activity against H. pylori DMST reference strain at MICs 4.6 and 10.8 μM, respectively, than that of the control metronidazole. Isojacareubin (8) displayed the most potent activity against H. pylori HP40 clinical isolate with MIC 23.9 μM, which was approximately two times greater than that of the standard drug amoxicillin.

  11. Phenotypic and Molecular Antimicrobial Susceptibility of Helicobacter pylori.

    PubMed

    Chen, Derrick; Cunningham, Scott A; Cole, Nicolynn C; Kohner, Peggy C; Mandrekar, Jayawant N; Patel, Robin

    2017-04-01

    Failure to eradicate Helicobacter pylori infection is often a result of antimicrobial resistance, which for clarithromycin is typically mediated by specific point mutations in the 23S rRNA gene. The purpose of this study was to define current patterns of antimicrobial susceptibility in H. pylori isolates derived primarily from the United States and to survey them for the presence of point mutations in the 23S rRNA gene and assess the ability of these mutations to predict phenotypic clarithromycin susceptibility. Antimicrobial susceptibility testing was performed using agar dilution on 413 H. pylori isolates submitted to Mayo Medical Laboratories for susceptibility testing. For a subset of these isolates, a 150-bp segment of the 23S rRNA gene was sequenced. A total of 1,970 MICs were reported over the 4-year study period. The rate of clarithromycin resistance was high (70.4%), and elevated MICs were frequently observed for metronidazole (82.4% of isolates had an MIC of >8 μg/ml) and ciprofloxacin (53.5% of isolates had an MIC of >1 μg/ml). A total of 111 archived H. pylori isolates underwent 23S rRNA gene sequencing; we found 95% concordance between genotypes and phenotypes (P = 0.9802). Resistance to clarithromycin was most commonly due to an A2143G mutation (82%), followed by A2142G (14%) and A2142C (4%) mutations. Clinical H. pylori isolates derived primarily from the United States demonstrated a high rate of clarithromycin resistance and elevated metronidazole and ciprofloxacin MICs. The relative distribution of point mutations at positions 2143 and 2142 in the 23S rRNA gene in clarithromycin-resistant H. pylori was similar to that reported from other parts of the world; these mutations predict phenotypic resistance to clarithromycin.

  12. Metabolic consequences of Helicobacter pylori infection and eradication

    PubMed Central

    Buzás, György Miklós

    2014-01-01

    Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future. PMID:24833852

  13. Helicobacter pylori eradication as a preventive tool against gastric cancer.

    PubMed

    Hamajima, Nobuyuki; Goto, Yasuyuki; Nishio, Kazuko; Tanaka, Daisuke; Kawai, Sayo; Sakakibara, Hisataka; Kondo, Takaaki

    2004-01-01

    Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

  14. Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach

    PubMed Central

    Huang, Julie Y.; Goers Sweeney, Emily; Guillemin, Karen

    2017-01-01

    Helicobacter pylori’s ability to respond to environmental cues in the stomach is integral to its survival. By directly visualizing H. pylori swimming behavior when encountering a microscopic gradient consisting of the repellent acid and attractant urea, we found that H. pylori is able to simultaneously detect both signals, and its response depends on the magnitudes of the individual signals. By testing for the bacteria’s response to a pure acid gradient, we discovered that the chemoreceptors