Serum TNF-α levels and Helicobacter pylori cagA and vacA genes

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Siregar, G. A.; Halim, S.; Sitepu, R. R.; Darmadi

2018-03-01

Helicobacter pylori is associated with higher virulence. TNF-α has an important role in host defense against H. pylori infection. The aim of this study was to investigate the relationship between TNF-α serum levels with cagA and vacA genes in H. pylori infection. This was a cross-sectional study involving 80 patients that consecutively admitted to endoscopy unit. Diagnosis of H. pylori infection was based on rapid urease test. Serum samples werecollected to determine circulating TNF-α level. Polymerase chain reaction was done to examine H. pylori vacA and cagA genes. Data analysis was carriedout using SPSS version 22 with 95%CI and p<0.05 was considered statistically significant. About 45 (56.3%) patients infected with Helicobacter pylori. There were 33 (73.3%) patients with H. pylori cagA positive. Serum TNF-α levels in patients with the H. pylori positive were significantly higher compared to H. pylori negative. Serum level of TNF-α was significantly higher in cagA positive than negative. Subjects with H. pylori cagA gene positive were more likely to have ahigher level of serum TNF-α than H. pylori cagA gene negative.

Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells.

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Amanda Oldani

2009-10-01

Full Text Available Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA(+/VacA(+H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its

cagA positive Helicobacter pylori in Brazilian children related to chronic gastritis

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Luciano Lobo Gatti

Full Text Available Helicobacter pylori is a spiral-shaped Gram-negative bacterium. It colonizes the gastric mucosa of humans and persists for decades if not treated. Helicobacter pylori infection affects more than half of the world's population and invariably results in chronic gastritis. The cagA gene is present in about 60 to 70% of H. pylori strains; it encodes a high-molecular-weight protein (120 to 140 kDa and several investigators have noted a correlation between strains that possess cagA and the severity of gastric mucosal inflammation. We examined the relation between cagA status in H. pylori strains and chronic gastritis with inflammatory processes in children from Marília, São Paulo, Brazil. One-hundred-twenty-one children were analyzed histopathologically and by polymerase chain reaction (PCR to detect H. pylori and cagA. We then looked for an association between cagA presence and inflammatory infiltration. Using histology and PCR, we found 47% H. pylori positive infection; 29 children were diagnosed with chronic gastritis, while 28 showed normal mucosa by histopathological analysis. CagA presence was genotyped in both groups, and an inflammatory infiltrate was studied in all infected children with chronic gastritis. We found cagA strains in 20 of 29 (69% children with chronic gastritis and 18 of 28 (64% with normal mucosa, demonstrating a strong relationship between the strains and the inflammatory process. We found a positive association between an inflammatory process associated with H. pylori of cagA+ strains and chronic gastritis development.

Prediction of extracellular proteases of the human pathogen Helicobacter pylori reveals proteolytic activity of the Hp1018/19 protein HtrA.

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Martin Löwer

Full Text Available Exported proteases of Helicobacter pylori (H. pylori are potentially involved in pathogen-associated disorders leading to gastric inflammation and neoplasia. By comprehensive sequence screening of the H. pylori proteome for predicted secreted proteases, we retrieved several candidate genes. We detected caseinolytic activities of several such proteases, which are released independently from the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI. Among these, we found the predicted serine protease HtrA (Hp1019, which was previously identified in the bacterial secretome of H. pylori. Importantly, we further found that the H. pylori genes hp1018 and hp1019 represent a single gene likely coding for an exported protein. Here, we directly verified proteolytic activity of HtrA in vitro and identified the HtrA protease in zymograms by mass spectrometry. Overexpressed and purified HtrA exhibited pronounced proteolytic activity, which is inactivated after mutation of Ser205 to alanine in the predicted active center of HtrA. These data demonstrate that H. pylori secretes HtrA as an active protease, which might represent a novel candidate target for therapeutic intervention strategies.

Expression of cagA, virB/D Complex and/or vacA Genes in Helicobacter pylori Strains Originating from Patients with Gastric Diseases.

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Andrzej Szkaradkiewicz

Full Text Available In order to better understand pathogenicity of Helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: cagA, virB/D complex (virB4, virB7, virB8, virB9, virB10, virB11, virD4 and vacA in strains of the pathogen originating from persons with gastric diseases. The studies were conducted on 42 strains of H. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-NAG (group 1, including subgroup 1 containing cagA+ isolates and subgroup 2 containing cagA- strains, multifocal atrophic gastritis-MAG (group 2 and gastric adenocarcinoma-GC (group 3. Expression of H. pylori genes was studied using microarray technology. In group 1, in all strains of H. pylori cagA+ (subgroup 1 high expression of the gene as well as of virB/D was disclosed, accompanied by moderate expression of vacA. In strains of subgroup 2 a moderate expression of vacA was detected. All strains in groups 2 and 3 carried cagA gene but they differed in its expression: a high expression was detected in isolates of group 2 and its hyperexpression in strains of group 3 (hypervirulent strains. In both groups high expression of virB/D and vacA was disclosed. Our results indicate that chronic active gastritis may be induced by both cagA+ strains of H. pylori, manifesting high expression of virB/D complex but moderate activity of vacA, and cagA- strains with moderate expression of vacA gene. On the other hand, in progression of gastric pathology and carcinogenesis linked to H. pylori a significant role was played by hypervirulent strains, manifesting a very high expression of cagA and high activity of virB/D and vacA genes.

Helicobacter pylori: focus on CagA and VacA major virulence factors Helicobacter pylori: enfoque sobre los factores de virulencia CagA y VacA

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Gonzalo Castillo-Rojas

2004-12-01

Full Text Available 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.Después de colonizar la mucosa gástrica humana, Helicobacter pylori puede permanecer por años e incluso décadas en el humano, y se asocia a varias patologías gástricas. En México, la seroprevalencia estimada es de 20% en niños de un año de edad, con una tasa de incremento en seropositividad de 5% anual durante los primeros 10 años de vida hasta alcanzar 80% en adultos jóvenes entre los 18 y 20 años de edad. Los factores bacterianos de virulencia propuestos para H. pylori son ureasa, flagelos, proteínas de choque térmico, lipopolisacárido, adhesinas, citotoxina vacuolizante, isla de patogenicidad y la proteína asociada a la citoxina; este último factor es el más estudiado hasta la fecha.

Role of the Helicobacter pylori virulence factors vacuolating cytotoxin, CagA, and urease in a mouse model of disease.

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Ghiara, P; Marchetti, M; Blaser, M J; Tummuru, M K; Cover, T L; Segal, E D; Tompkins, L S; Rappuoli, R

1995-10-01

The pathogenic role of Helicobacter pylori virulence factors has been studied with a mouse model of gastric disease. BALB/c mice were treated orally with different amounts of sonic extracts of cytotoxic H. pylori strains (NCTC 11637, 60190, 84-183, and 87A300 [CagA+/Tox+]). The pathological effects on histological sections of gastric mucosae were assessed and were compared with the effects of treatments with extracts from noncytotoxic strains (G21 and G50 [CagA-/Tox-]) and from strains that express either CagA alone (D931 [CagA+/Tox-]) or the cytotoxin alone (G104 [CagA-/Tox+]). The treatment with extracts from cytotoxic strains induced various epithelial lesions (vacuolation, erosions, and ulcerations), recruitment of inflammatory cells in the lamina propria, and a marked reduction of the mucin layer. Extracts of noncytotoxic strains induced mucin depletion but no other significant pathology. Crude extracts of strain D931, expressing CagA alone, caused only mild infiltration of inflammatory cells, whereas extracts of strain G104, expressing cytotoxin alone, induced extensive epithelial damage but little inflammatory reaction. Loss of the mucin layer was not associated with a cytotoxic phenotype, since this loss was observed in mice treated with crude extracts of all strains. The pathogenic roles of CagA, cytotoxin, and urease were further assessed by using extracts of mutant strains of H. pylori defective in the expression of each of these virulence factors. The results obtained suggest that (i) urease activity does not play a significant role in inducing the observed gastric damage, (ii) cytotoxin has an important role in the induction of gastric epithelial cell lesions but not in eliciting inflammation, and (iii) other components present in strains which carry the cagA gene, but distinct from CagA itself, are involved in eliciting the inflammatory response.

Distribution of Helicobacter pylori cagA, cagE, oipA and vacA in different major ethnic groups in Tehran, Iran.

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Dabiri, Hossein; Maleknejad, Parviz; Yamaoka, Yoshio; Feizabadi, Mohammad M; Jafari, Fereshteh; Rezadehbashi, Maryam; Nakhjavani, Farrokh A; Mirsalehian, Akbar; Zali, Mohammad R

2009-08-01

There are geographical variations in Helicobacter pylori virulence genes; cagA, cagE, vacA and oipA. The present study compared the distribution of these genotypes in major ethnic groups residing in Tehran, Iran and their association with clinical outcomes. A total of 124 H. pylori-positive patients living in Tehran were enrolled in this study. The ethnic distribution was 74 Persians, 33 Turks and 17 other ethnics including Kurds, Lurs, Afghanis and Arabs. The presence of the cagA, cagE and oipA genes and vacA alleles (signal [s] and middle [m] region) were determined by polymerase chain reaction (PCR) from H. pylori DNA. The cagA-positive status was predominant in all three ethnic groups (e.g. 65% in Persians and 73% in Turks). In contrast, the cagE-positive status was less than half in Persians (47%) and Turks (30%), whereas it was 77% in other ethnicities (P = 0.008). The predominant vacA genotypes were s1 and m1 in all three ethnic groups (e.g. 68% in Persians and 70% in Turks were s1). There was no significant association between cagA and cagE status or vacA genotypes and clinical outcomes. The oipA-positive strains were more common in non-ulcer dyspepsia (NUD) (63%) than in peptic ulcer patients (15%) (P = 0.001) in Persians, but the association was not observed in other ethnic groups. There are some differences in the H. pylori genotypes among the ethnic groups in Iran. However, none of these markers seemed to be clinically helpful in predicting the clinical presentation of a H. pylori infection in Iran.

Detection of Helicobacter pylori CagA gene and Its Association with Endoscopic Appearance in Balinese Dyspepsia Patients

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I Ketut Mariadi

2016-09-01

Full Text Available Background: Helicobacter pylori (H. pylori infection causes various abnormalities in the stomach. Only particular strain can cause severe problems in the stomach. CagA is a microbial virulent factor which is associated with more severe stomach problems, such as: peptic ulcer and stomach cancer. We would like to know the prevalence of CagA in Balinese population, and the association of H. Pylori CagA status with the severity of endoscopic appearance in dyspepsia patients. Method: Study design being used was analytic cross sectional study, involving 71 dyspepsia patients who underwent upper gastrointestinal endoscopic examination in Surya Husada Hospital and Balimed Hospital in June-December 2013. Sample was chosen in consecutive manner. Later, polymerase chain reaction (PCR examinations of the stomach mucous biopsy tissue to determine H. pylori infection status and CagA status were performed. Further, Chi square test was used to identify the difference in proportion of H. pylori and CagA between mild and severe endoscopic appearance. Results: In this study, we found that the prevalence of H. pylori infection was 22.5% using PCR examination. Prevalence of CagA positive in H. pylori positive was 62.5%. There was significant association between status of H. Pylori infection and severity of endoscopic appearance (p = 0.038; OR= 2.67; 95% CI = 1.18-6.05. Status of CagA in H. pylori infected patients was not associated with the severity of endoscopic appearance. Additionally, there was significant association between patients’ age and severity of endoscopic appearance. Conclusion: The prevalence of CagA in H. pylori positive was 62.5%. H. pylori infection was associated with severity of endoscopic appearance and CagA status in H. pylori infected patients was not associated with severity of endoscopic appearance.

A transgenic Drosophila model demonstrates that the Helicobacter pylori CagA protein functions as a eukaryotic Gab adaptor.

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Crystal M Botham

2008-05-01

Full Text Available Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The cytotoxin-associated gene A (CagA protein of H. pylori, which is translocated into host cells via a type IV secretion system, is a major risk factor for disease development. Experiments in gastric tissue culture cells have shown that once translocated, CagA activates the phosphatase SHP-2, which is a component of receptor tyrosine kinase (RTK pathways whose over-activation is associated with cancer formation. Based on CagA's ability to activate SHP-2, it has been proposed that CagA functions as a prokaryotic mimic of the eukaryotic Grb2-associated binder (Gab adaptor protein, which normally activates SHP-2. We have developed a transgenic Drosophila model to test this hypothesis by investigating whether CagA can function in a well-characterized Gab-dependent process: the specification of photoreceptors cells in the Drosophila eye. We demonstrate that CagA expression is sufficient to rescue photoreceptor development in the absence of the Drosophila Gab homologue, Daughter of Sevenless (DOS. Furthermore, CagA's ability to promote photoreceptor development requires the SHP-2 phosphatase Corkscrew (CSW. These results provide the first demonstration that CagA functions as a Gab protein within the tissue of an organism and provide insight into CagA's oncogenic potential. Since many translocated bacterial proteins target highly conserved eukaryotic cellular processes, such as the RTK signaling pathway, the transgenic Drosophila model should be of general use for testing the in vivo function of bacterial effector proteins and for identifying the host genes through which they function.

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

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Sungil Jang

2017-02-01

Full Text Available 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.

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

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

2015-01-01

Our aim was to determine the EPIYA-cagA Phosphorylation sites and dupA gene in H. pylori isolates among patients with upper gastrointestinal diseases. 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. 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. 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). 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.

Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer.

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Martínez-Carrillo, D N; Atrisco-Morales, J; Hernández-Pando, R; Reyes-Navarrete, S; Betancourt-Linares, R; Cruz-del Carmen, I; Illades Aguiar, B; Román-Román, A; Fernández-Tilapa, G

2014-01-01

Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.

Evolution of cagA oncogene of Helicobacter pylori through recombination.

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Yoshikazu Furuta

Full Text Available Helicobacter pylori is a gastric pathogen that infects half the human population and causes gastritis, ulcers, and cancer. The cagA gene product is a major virulence factor associated with gastric cancer. It is injected into epithelial cells, undergoes phosphorylation by host cell kinases, and perturbs host signaling pathways. CagA is known for its geographical, structural, and functional diversity in the C-terminal half, where an EPIYA host-interacting motif is repeated. The Western version of CagA carries the EPIYA segment types A, B, and C, while the East Asian CagA carries types A, B, and D and shows higher virulence. Many structural variants such as duplications and deletions are reported. In this study, we gained insight into the relationships of CagA variants through various modes of recombination, by analyzing all known cagA variants at the DNA sequence level with the single nucleotide resolution. Processes that occurred were: (i homologous recombination between DNA sequences for CagA multimerization (CM sequence; (ii recombination between DNA sequences for the EPIYA motif; and (iii recombination between short similar DNA sequences. The left half of the EPIYA-D segment characteristic of East Asian CagA was derived from Western type EPIYA, with Amerind type EPIYA as the intermediate, through rearrangements of specific sequences within the gene. Adaptive amino acid changes were detected in the variable region as well as in the conserved region at sites to which no specific function has yet been assigned. Each showed a unique evolutionary distribution. These results clarify recombination-mediated routes of cagA evolution and provide a solid basis for a deeper understanding of its function in pathogenesis.

Helicobacter pylori virulence genes in the five largest islands of Indonesia.

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Miftahussurur, Muhammad; Syam, Ari Fahrial; Makmun, Dadang; Nusi, Iswan Abbas; Zein, Lukman Hakim; Zulkhairi; Akil, Fardah; Uswan, Willi Brodus; Simanjuntak, David; Uchida, Tomohisa; Adi, Pangestu; Utari, Amanda Pitarini; Rezkitha, Yudith Annisa Ayu; Subsomwong, Phawinee; Nasronudin; Yamaoka, Yoshio

2015-01-01

It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors. The genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system. A total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-type-cagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/β-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/β-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/β-(1,3)galT type among different ethnic groups (P dupA negative or short type dupA, and the jhp0562/β-(1,3)galT double positive genotype.

Helicobacter pylori promotes the expression of Krüppel-like factor 5, a mediator of carcinogenesis, in vitro and in vivo.

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Jennifer M Noto

Full Text Available Helicobacter pylori is the strongest known risk factor for the development of gastric adenocarcinoma. H. pylori expresses a repertoire of virulence factors that increase gastric cancer risk, including the cag pathogenicity island and the vacuolating cytotoxin (VacA. One host element that promotes carcinogenesis within the gastrointestinal tract is Krüppel-like factor 5 (KLF5, a transcription factor that mediates key cellular functions. To define the role of KLF5 within the context of H. pylori-induced inflammation and injury, human gastric epithelial cells were co-cultured with the wild-type cag(+ H. pylori strain 60190. KLF5 expression was significantly upregulated following co-culture with H. pylori, but increased expression was independent of the cag island or VacA. To translate these findings into an in vivo model, C57BL/6 mice were challenged with the wild-type rodent-adapted cag(+ H. pylori strain PMSS1 or a PMSS1 cagE(- isogenic mutant. Similar to findings in vitro, KLF5 staining was significantly enhanced in gastric epithelium of H. pylori-infected compared to uninfected mice and this was independent of the cag island. Flow cytometry revealed that the majority of KLF5(+ cells also stained positively for the stem cell marker, Lrig1, and KLF5(+/Lrig1(+ cells were significantly increased in H. pylori-infected versus uninfected tissue. To extend these results into the natural niche of this pathogen, levels of KLF5 expression were assessed in human gastric biopsies isolated from patients with or without premalignant lesions. Levels of KLF5 expression increased in parallel with advancing stages of neoplastic progression, being significantly elevated in gastritis, intestinal metaplasia, and dysplasia compared to normal gastric tissue. These results indicate that H. pylori induces expression of KLF5 in gastric epithelial cells in vitro and in vivo, and that the degree of KLF5 expression parallels the severity of premalignant lesions in human

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

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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 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.

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

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Xue-Song Zhang

2015-02-01

Full Text Available 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.

CagA-positive Helicobacter pylori infection is not associated with decreased risk of Barrett's esophagus in a population with high H. pylori infection rate

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Ortego Javier

2006-02-01

Full Text Available Abstract Background & aim The role that H. pylori infection plays in the development of and Barrett's esophagus (BE is uncertain. We tested the hypothesis that infection with cagA+ Helicobacter pylori strains protects against the development of BE. Methods We studied 104 consecutive patients, residents in an area with a high prevalence of H. pylori infection, with BE and 213 sex- and age-matched controls. H. pylori infection and CagA antibody status were determined by western blot serology. Results H. pylori prevalence was higher in patients with BE than in controls (87.5% vs. 74.6%; OR. 2.3; 95% CI: 1.23–4.59. Increasing age was associated with a higher prevalence of H. pylori (p Conclusion Neither H. pylori infection nor H. pylori infection by CagA+ strains reduce the risk of BE in a population with high prevalence of H. pylori infection.

Inhibitory Effects of Anthocyanins on Secretion of Helicobacter pylori CagA and VacA Toxins

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Kim, Sa-Hyun; Park, Min; Woo, Hyunjun; Tharmalingam, Nagendran; Lee, Gyusang; Rhee, Ki-Jong; Eom, Yong Bin; Han, Sang Ik; Seo, Woo Duck; Kim, Jong Bae

2012-01-01

Anthocyanins have been studied as potential antimicrobial agents against Helicobacter pylori. We investigated whether the biosynthesis and secretion of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190 (CagA+/VacA+) was used in this study to investigate the inhibitory effects of anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G), pelargonidin 3-O-glucoside (Pel3G), and malvidin 3-O-glucoside (M3G) on expression and secretion of H. pylori toxins. Anthocyanins were added to bacterial cultures and Western blotting was used to determine secretion of CagA and VacA. Among them, we found that C3G inhibited secretion of CagA and VacA resulting in intracellular accumulation of CagA and VacA. C3G had no effect on cagA and vacA expression but suppressed secA transcription. As SecA is involved in translocation of bacterial proteins, the down-regulation of secA expression by C3G offers a mechanistic explanation for the inhibition of toxin secretion. To our knowledge, this is the first report suggesting that C3G inhibits secretion of the H. pylori toxins CagA and VacA via suppression of secA transcription. PMID:23155357

Conformational analysis of isolated domains of Helicobacter pylori CagA.

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Amanda P Woon

Full Text Available The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation--a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions.

Phylogeographic diversity and mosaicism of the Helicobacter pylori tfs integrative and conjugative elements.

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Delahay, Robin M; Croxall, Nicola J; Stephens, Amberley D

2018-01-01

The genome of the gastric pathogen Helicobacter pylori is characterised by considerable variation of both gene sequence and content, much of which is contained within three large genomic islands comprising the cag pathogenicity island ( cag PAI) and two mobile integrative and conjugative elements (ICEs) termed tfs3 and tfs4 . All three islands are implicated as virulence factors, although whereas the cag PAI is well characterised, understanding of how the tfs elements influence H. pylori interactions with different human hosts is significantly confounded by limited definition of their distribution, diversity and structural representation in the global H. pylori population. To gain a global perspective of tfs ICE population dynamics we established a bioinformatics workflow to extract and precisely define the full tfs pan-gene content contained within a global collection of 221 draft and complete H. pylori genome sequences. Complete (ca. 35-55kbp) and remnant tfs ICE clusters were reconstructed from a dataset comprising > 12,000 genes, from which orthologous gene complements and distinct alleles descriptive of different tfs ICE types were defined and classified in comparative analyses. The genetic variation within defined ICE modular segments was subsequently used to provide a complete description of tfs ICE diversity and a comprehensive assessment of their phylogeographic context. Our further examination of the apparent ICE modular types identified an ancient and complex history of ICE residence, mobility and interaction within particular H. pylori phylogeographic lineages and further, provided evidence of both contemporary inter-lineage and inter-species ICE transfer and displacement. Our collective results establish a clear view of tfs ICE diversity and phylogeographic representation in the global H. pylori population, and provide a robust contextual framework for elucidating the functional role of the tfs ICEs particularly as it relates to the risk of gastric

Inhibition of Helicobacter pylori CagA-Induced Pathogenesis by Methylantcinate B from Antrodia camphorata

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Chun-Jung Lin

2013-01-01

Full Text Available The bacterial pathogen Helicobacter pylori (Hp is the leading risk factor for the development of gastric cancer. Hp virulence factor, cytotoxin-associated gene A (CagA interacted with cholesterol-enriched microdomains and leads to induction of inflammation in gastric epithelial cells (AGS. In this study, we identified a triterpenoid methylantcinate B (MAB from the medicinal mushroom Antrodia camphoratawhich inhibited the translocation and phosphorylation of CagA and caused a reduction in hummingbird phenotype in HP-infected AGS cells. Additionally, MAB suppressed the Hp-induced inflammatory response by attenuation of NF-κB activation, translocation of p65 NF-κB, and phosphorylation of IκB-α, indicating that MAB modulates CagA-mediated signaling pathway. Additionally, MAB also suppressed the IL-8 luciferase activity and its secretion in HP-infected AGS cells. On the other hand, molecular structure simulations revealed that MAB interacts with CagA similarly to that of cholesterol. Moreover, binding of cholesterol to the immobilized CagA was inhibited by increased levels of MAB. Our results demonstrate that MAB is the first natural triterpenoid which competes with cholesterol bound to CagA leading to attenuation of Hp-induced pathogenesis of epithelial cells. Thus, this study indicates that MAB may have a scope to develop as a therapeutic candidate against Hp CagA-induced inflammation.

Helicobacter pylori Diversity and Gastric Cancer Risk

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Timothy L. Cover

2016-03-01

Full Text Available Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI. Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed.

An inverse relationship between CagA+ strains of Helicobacter pylori infection and risk of erosive GERD

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Somi, Mohammad H.; Fattahi, E.; Fouladi, Rohollah F.; Karimi, M.; Bonyadi, R.; Baballou, Z.

2008-01-01

The aim of this study is investigating the association of Helicobacter pylori (H. pylori) infection and its cytogenetic-associated gene A (cag A) strain with reflux esophagitis. In a case-control setting (May 2005-2006), patients with reflux esophagitis (case group) were compared with age and gender matched people suffering from symptoms of gastroesophageal reflux disease with normal upper gastrointestinal endoscopic findings (control group) in Imam Khomeini Hospital, Tabriz, Iran. The rates of H. pylori and its cagA positive infections were separately compared between the 2 groups and the subgroups with different severity of reflux esophagitis. Ninety-two and 93 patients were enrolled in the case and control groups. The rate of H.pylori infection was significantly lower in case group (81.5%versus 87.10%, p=0.29, odd ratio 0.654, 95% confidence interval [CI] 0.293 to 1.495). The CagA positive infections were found significantly more frequent in the control group (59.1% versus 40.2%, p=0.01, odd ratio 0.465, 95% CI 0.258 to 0.836). There was no significant difference between the severity subgroups of the disease for H. pylori (p=0.30) or cagA positive infection rates (p=0.40). The cagA positive strains might have a protective effect against reflux esophagitis. (author)

Association of Vac A- and Cag A-specific Helicobacter pylori strain infection with spontaneous preterm birth.

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Yang, Seung Woo; Kwon, Han Sung; Sohn, In Sook; Kim, Young Ju; Hwang, Han Sung

2017-04-01

To better understand the correlation between Helicobacter pylori (H. pylori) seropositivity and spontaneous preterm birth. A total of 320 pregnant women were classified into two groups: normal control singleton pregnant group (n = 264) and singleton spontaneous preterm birth group (n = 56). Blood samples were collected at the time of delivery, and the H. pylori IgG, various virulence factors and systemic inflammation status were compared between the two groups. Between the two groups, the serum H. pylori IgG, Cytotoxin-associated agntigen A (Cag A), Vacuolating cytotoxin A (Vac A) significantly increased in spontaneous preterm birth group than in the control group. Also, in preterm group, highly sensitive C-reactive protein (hsCRP) as a systemic inflammatory marker is statistically elevated at inflammatory status range. Whereas in the term pregnant group, hsCRP was normal range even though high incidence of H. pylori IgG seropositivity. Also, in the seropositive group, hsCRP is statistically correlated with H. pylori IgG, Cag A and Vac A. There is an association between the presence of antibodies against H. pylori in maternal serum and the development of preterm birth. Furthermore, serology type of H. pylori with Vac A, Cag A relates to preterm birth even though high H. pylori prevalence rate.

Infecção por Helicobacter pylori e câncer gástrico: freqüência de cepas patogênicas cagA e vacA em pacientes com câncer gástrico Helicobacter pylori and gastric cancer: distribution of cagA and vacA genotypes in patients with gastric carcinoma

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Cristiane Melissa Thomazini

2006-02-01

the human stomach by pathogenic Helicobacter pylori strains. OBJECTIVE: To investigate the distribution of cagA and vacA genotypes of Helicobacter pylori in paraffin-embedded gastric samples from patients with gastric cancer. MATERIAL AND METHODS: Paraffin-embedded samples from 42 patients with gastric cancer were histologically examined and evaluated by PCR for H. pylori cagA and vacA (s and m regions genotypes. RESULTS: Histological analysis allowed direct visualization of H. pylori in 85.7% of cases and PCR for urease C gene detected H. pylori in 95% of cases. The presence of cagA gene was detected in 23 (54.7% patients with gastric cancer. The s1 allele from vacA gene was found in samples from 24 (57.1% patients and the m1 allele in 26 (61.9 %. The s1m1 genotype was detected in 24 (57.1% patients with gastric cancer. The s2 allele was found in samples from four patients (9.5% and the m2 allele in three (7.1% patients. The distribution of H. pylori genotypes was similar in both intestinal and diffuse types of gastric carcinoma. CONCLUSION: Our results confirm the relevance of the pathogenic cagA and vacA H. pylori genotypes for significant organic lesions, such as gastric cancer, suggesting a possible role for H. pylori in the pathogenesis of gastric carcinoma.

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

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Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

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.

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

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

2014-01-01

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

Prevalence of Helicobacter pylori cagA, babA2, and dupA genotypes and correlation with clinical outcome in Malaysian patients with dyspepsia.

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Osman, Hussein Ali; Hasan, Habsah; Suppian, Rapeah; Hassan, Syed; Andee, Dzulkarnaen Zakaria; Abdul Majid, Noorizan; Zilfalil, Bin-alwi

2015-01-01

The severity of disease outcome in dyspepsia has been attributed to Helicobacter pylori virulence genes. The aim of this study was to determine the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to determine whether or not there arises a significant correlation with clinical dyspepsia outcomes. H. pylori genotypes cagA, babA2, and dupA were identified by polymerase chain reactions from gastric biopsy samples in 105 H. pylori-positive patients. The positive rates for cagA, babA2, and dupA genes in H. pylori dyspeptic patients were 69.5%, 41.0%, and 22.9%, respectivel cagA was more prevalent in Indians (39.7%), babA2 was more prevalent in Malays (39.5%), and dupA detection occurred more frequently in both Indians and Malays and at the same rate (37.5%). The Chinese inhabitants had the lowest prevalence of the three genes. Nonulcer disease patients had a significantly higher distribution of cagA (76.7%), babA2 (74.4%), and dupA (75.0%). There was no apparent association between these virulence genes and the clinical outcomes. The lower prevalence of these genes and variations among different ethnicities implies that the strains are geographically and ethnically dependent. None of the virulence genes were knowingly beneficial in predicting the clinical outcome of H. pylori infection in our subjects.

Prevalence of Helicobacter pylori vacA Genotypes and cagA Gene in Dental Plaque of Asymptomatic Mexican Children

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Mendoza-Cantú, Alejandra; Urbina-Ríos, Cynthia Sofía; García-Martínez, Martha Elena; Torre-Martínez, Hilda H. H.

2017-01-01

The variability in Helicobacter pylori vacA and cagA genes has been related to the progression of the gastrointestinal disease; also the presence of H. pylori in the oral cavity has been associated with periodontal disease in adults, but, in children without dyspeptic symptoms, little is known about this. We evaluated the prevalence of H. pylori and the presence of vacA/cagA genotypes in the oral cavity of Mexican children without dyspeptic symptoms. The gingival status was measured, and dental plaque samples (n = 100) were taken. 38% of children were positive for H. pylori 16S rRNA gene by qPCR. A significant association between H. pylori oral infection and gingival status was observed (P < 0.001). In 34.6% (9/26) of mild gingivitis cases, s1m2 genotype was found, while s1m1 was typed in 50% (3/6) of moderate gingivitis. The cagA prevalence among H. pylori-positive children was 80.8% (21/26), 83.3% (5/6), and 16.7% (1/6) of cases of mild gingivitis, moderate gingivitis, and nongingivitis, respectively (P < 0.001). The s1m1/cagA+ combinational genotype was the most detected in children with gingivitis. Our results suggest that the prevalence of H. pylori and detection of vacA/cagA genotypes-associated gastrointestinal disease in the oral cavity could be related to the progression of gingivitis in asymptomatic children. PMID:29226140

Prevalence of Helicobacter pylori vacA Genotypes and cagA Gene in Dental Plaque of Asymptomatic Mexican Children

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Alejandra Mendoza-Cantú

2017-01-01

Full Text Available The variability in Helicobacter pylori vacA and cagA genes has been related to the progression of the gastrointestinal disease; also the presence of H. pylori in the oral cavity has been associated with periodontal disease in adults, but, in children without dyspeptic symptoms, little is known about this. We evaluated the prevalence of H. pylori and the presence of vacA/cagA genotypes in the oral cavity of Mexican children without dyspeptic symptoms. The gingival status was measured, and dental plaque samples (n=100 were taken. 38% of children were positive for H. pylori 16S rRNA gene by qPCR. A significant association between H. pylori oral infection and gingival status was observed (P<0.001. In 34.6% (9/26 of mild gingivitis cases, s1m2 genotype was found, while s1m1 was typed in 50% (3/6 of moderate gingivitis. The cagA prevalence among H. pylori-positive children was 80.8% (21/26, 83.3% (5/6, and 16.7% (1/6 of cases of mild gingivitis, moderate gingivitis, and nongingivitis, respectively (P<0.001. The s1m1/cagA+ combinational genotype was the most detected in children with gingivitis. Our results suggest that the prevalence of H. pylori and detection of vacA/cagA genotypes-associated gastrointestinal disease in the oral cavity could be related to the progression of gingivitis in asymptomatic children.

CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

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Nina Bertaux-Skeirik

2015-02-01

Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

CagI is an essential component of the Helicobacter pylori Cag type IV secretion system and forms a complex with CagL.

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Kieu Thuy Pham

Full Text Available Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly.

Alterations in Helicobacter pylori triggered by contact with gastric epithelial cells

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Elizabeth M. Johnson

2012-02-01

Full Text Available Helicobacter pylori lives within the mucus layer of the human stomach, in close proximity to gastric epithelial cells. While a great deal is known about the effects of H. pylori on human cells and the specific bacterial products that mediate these effects, relatively little work has been done to investigate alterations in H. pylori that may be triggered by bacterial contact with human cells. In this review, we discuss the spectrum of changes in bacterial physiology and morphology that occur when H. pylori is in contact with gastric epithelial cells. Several studies have reported that cell contact causes alterations in H. pylori gene transcription. In addition, H. pylori contact with gastric epithelial cells promotes the formation of pilus-like structures at the bacteria-host cell interface. The formation of these structures requires multiple genes in the cag pathogenicity island, and these structures are proposed to have an important role in the type IV secretion system-dependent process through which CagA enters host cells. Finally, H. pylori contact with epithelial cells can promote bacterial replication and the formation of microcolonies, phenomena that are facilitated by the acquisition of iron and other nutrients from infected cells. In summary, the gastric epithelial cell surface represents an important niche for H. pylori, and upon entry into this niche, the bacteria alter their behavior in a manner that optimizes bacterial proliferation and persistent colonization of the host.

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients

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Yalda Lucero

2017-08-01

Full Text Available HIGHLIGHTSWhat is already known about this subject?Celiac disease (CD has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors in CD have not yet completely elucidated.What are the new findings?cagA+ H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients.Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD remain elusive. Helicobacter pylori (Hp chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains in CD is unclear.Objective: To assess the relationship between gastric Hp infection (cagA+ strains and duodenal histological damage in patients with CD.Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed.Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30–40%, but cag

Macrophage migration inhibitory factor stimulated by Helicobacter pylori increases proliferation of gastric epithelial cells

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Xia, Harry Hua-Xiang; Lam, Shiu Kum; Chan, Annie O.O.; Lin, Marie Chia Mi; Kung, Hsiang Fu; Ogura, Keiji; Berg, Douglas E.; Wong, Benjamin C. Y.

2005-01-01

AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro. METHODS: A cytotoxic wild-type H pylori strain (TN2)and its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter. RESULTS: The wild-type strain and the isogenic mutants, TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared. CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H

Comparative analysis of the full genome of Helicobacter pylori isolate Sahul64 identifies genes of high divergence.

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Lu, Wei; Wise, Michael J; Tay, Chin Yen; Windsor, Helen M; Marshall, Barry J; Peacock, Christopher; Perkins, Tim

2014-03-01

Isolates of Helicobacter pylori can be classified phylogeographically. High genetic diversity and rapid microevolution are a hallmark of H. pylori genomes, a phenomenon that is proposed to play a functional role in persistence and colonization of diverse human populations. To provide further genomic evidence in the lineage of H. pylori and to further characterize diverse strains of this pathogen in different human populations, we report the finished genome sequence of Sahul64, an H. pylori strain isolated from an indigenous Australian. Our analysis identified genes that were highly divergent compared to the 38 publically available genomes, which include genes involved in the biosynthesis and modification of lipopolysaccharide, putative prophage genes, restriction modification components, and hypothetical genes. Furthermore, the virulence-associated vacA locus is a pseudogene and the cag pathogenicity island (cagPAI) is not present. However, the genome does contain a gene cluster associated with pathogenicity, including dupA. Our analysis found that with the addition of Sahul64 to the 38 genomes, the core genome content of H. pylori is reduced by approximately 14% (∼170 genes) and the pan-genome has expanded from 2,070 to 2,238 genes. We have identified three putative horizontally acquired regions, including one that is likely to have been acquired from the closely related Helicobacter cetorum prior to speciation. Our results suggest that Sahul64, with the absence of cagPAI, highly divergent cell envelope proteins, and a predicted nontransportable VacA protein, could be more highly adapted to ancient indigenous Australian people but with lower virulence potential compared to other sequenced and cagPAI-positive H. pylori strains.

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

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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.

Inhibitory Effects of Anthocyanins on Secretion of Helicobacter pylori CagA and VacA Toxins

OpenAIRE

Sa-Hyun Kim, Min Park, Hyunjun Woo, Nagendran Tharmalingam, Gyusang Lee, Ki-Jong Rhee, Yong Bin Eom, Sang Ik Han, Woo Duck Seo, Jong Bae Kim

2012-01-01

Anthocyanins have been studied as potential antimicrobial agents against Helicobacter pylori. We investigated whether the biosynthesis and secretion of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190 (CagA+/VacA+) was used in this study to investigate the inhibitory effects of anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G), pelargonidin 3-O-glucoside (Pe...

vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.

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Atrisco-Morales, Josefina; Martínez-Santos, Verónica I; Román-Román, Adolfo; Alarcón-Millán, Judit; De Sampedro-Reyes, José; Cruz-Del Carmen, Iván; Martínez-Carrillo, Dinorah N; Fernández-Tilapa, Gloria

2018-03-01

Virulent genotypes of Helicobacter pylori vacA s1m1/cagA + /babA2 + have been associated with severe gastric diseases. VacA, CagA and BabA are polymorphic proteins, and their association with the disease is allele-dependent. The aims of this work were: (i) to determine the prevalence of H. pylori by type of chronic gastritis; (ii) to describe the frequency of cagA, babA2 and vacA genotypes in strains from patients with different types of chronic gastritis; (iii) to characterize the variable region of cagA alleles. A total of 164 patients with chronic gastritis were studied. Altogether, 50 H. pylori strains were isolated, and the status of cagA, babA2 and vacA genotypes was examined by PCR. cagA EPIYA segment identification was performed using PCR and sequencing of cagA fragments of six randomly selected strains.Results/Key findings. The overall prevalence of H. pylori was 30.5 %. Eighty percent of the isolated strains were vacA s1m1, and the cagA and babA2 genes were detected in 74 and 32 % of the strains, respectively. The most frequent genotypes were vacA s1m1/cagA + /babA2 - and vacA s1m1/cagA + /babA2 + , with 40 % (20/50) and 28 % (14/50), respectively. In cagA + , the most frequent EPIYA motif was -ABC (78.4 %), and EPIYA-ABCC and -ABCCC motifs were found in 10.8 % of the strains. A modified EPIYT-B motif was found in 66.6 % of the sequenced strains. H. pylori strains carrying vacA s1m1, cagA + and babA2 - genotypes were the most prevalent in patients with chronic gastritis from the south of Mexico. In the cagA + strains, the EPIYA-ABC motif was the most common.

Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity

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Loh, John T.; Shaffer, Carrie L.; Piazuelo, M. Blanca; Bravo, Luis E.; McClain, Mark S.; Correa, Pelayo; Cover, Timothy L.

2011-01-01

BACKGROUND Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis. METHODS We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain. RESULTS A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathological analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif. CONCLUSIONS CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk. IMPACT These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not. PMID:21859954

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

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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.

High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer.

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Yolanda López-Vidal

Full Text Available BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008, and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003. A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036. A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003. Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.

Prevalence and Correlation with Clinical Diseases of Helicobacter pylori cagA and vacA Genotype among Gastric Patients from Northeast China

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Faisal Aziz

2014-01-01

Full Text Available Helicobacter pylori vacA and cagA genes have significant genetic heterogenicity, resulting in different clinical outcomes. Northeast part of China has reported high prevalence of H. pylori infections and gastric cancer. Hence, we investigated the H. pylori cagA and vacA genotypes with clinical outcomes in Northeast China. Gastric tissue samples (n=169, chronic gastritis (GIs, gastric ulcer (GU, and gastric cancer (GC were analysed for 16S rRNA ureA, cagA, and cagA genotypes by PCR. A total of 141 (84% cases were found positive for H. pylori by 16S rRNA and ureA. GC showed high H. pylori infection (93% compared with GIs (72% and GU (84%. The vacAs1am1 was highly found in GC (40% and GU (36%, vacAs1am2 in GIs (33%, vacAs1bm1 (14% and vacAs1bm2 (8% in GU cases, and s2m1 in normal cases (33%, while vacAs1cm1 showed low frequency in GIs (2% and GU (3% and GC showed negative result. The East-Asian cagA strain was highly observed in GC (43%, as compared to GIs (41% and GU (20%. The East-Asian cagA/vacAs1am1 was significantly higher in GC (23% than in GU (22% and GIs (145 patients. The East-Asian type cagA with vacAs1a and vacAm1 is the most predominant genotype in H. pylori strains of Northeast China.

Helicobacter pylori cagA and iceA genotypes status and risk of peptic ulcer in Saudi patients

International Nuclear Information System (INIS)

Momenah, Aiman M.; Tayeb, Mohammad T.

2007-01-01

Objective was to determine the prevalence of cagA+ and iceA genotypes among Helicobacter pylori (H. pylori) isolates from a group of Saudi patients with gastric complaints, and to find out any significant correlation between these strains and severe gastric clinical outcomes such as peptic ulcer and gastric cancer in Saudi population. A total of 1104 gastric biopsies from 368 patients who presented with symptoms suggestive of chronic gastritis, peptic ulcer disease, or gastric carcinoma were taken from the main hospitals in the Western region of Saudi Arabia from July 2004 to July 2005. We cultured the samples for H. pylori and a polymerase chain reaction was carried out to check for the presence or absence of cagA gene and the status of iceA genotypes. Among the 368 suspected patients to be infected with H. pylori by means of clinical features and endoscopic findings; 103 (28%) were positive using culture technique. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (p=0.0001). Furthermore, this study revealed that 100% of ulcer cases were infected with iceA1 with a statistically significant correlation (p=0.0001), while 94.6% of gastritis and 90.9% of normal were infected with iceA2 (p=0.0001). Moreover cagA+/iceA1 combined genotypes was statistically correlated with peptic ulcer (100%) but not cagA-/iceA1 (0%; p=0.0001).Certain H. pylori genotypes were more virulent than others. Multiple clinical implications based on these finding might be studied further.(author)

Soroprevalência de anticorpos contra o antígeno CagA do Helicobacter pylori em pacientes com úlcera gástrica na região Norte do Brasil Seroprevalence of antibodies against the CagA antigen the Helicobacter pylori in patients with gastric ulcer in the North region of Brazil

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Luisa Caricio Martins

2002-08-01

Full Text Available O Helicobacter pylori é um agente patogênico largamente distribuído no mundo, estando envolvido no desenvolvimento de várias doenças gastrointestinais. Atualmente a infecção pela cepa virulenta (CagA+ do H. pylori é considerado um dos principais fatores etiológicos para o desenvolvimento de ulcerações gástricas. Baseado nessa informação, investigamos a soroprevalência das cepas virulentas entre os pacientes com úlcera gástrica da nossa região, utilizando testes sorológicos para detecção de anticorpos contra o H. pylori e a proteína CagA. Sendo observado que 82% (45/55 dos pacientes estavam infectados pela cepa virulenta, entre esses 89% (40/45 apresentaram grau de inflamação aumentado na mucosa gástrica, com denso infiltrado de leucócitos no tecido, o que provavelmente favoreceu a formação das ulcerações gástricas.Helicobacter pylori is a pathogenic agent with a worldwide distribution and is involved in the development of many gastrointestinal diseases. Nowadays infection with the virulent strain CagA+ of H. pylori is considered one of the main etiological factors in the development of gastric ulcer. Based on this information, we investigated the seroprevalence of virulent strains among patients with gastric ulcer from one region, using serologic tests to detect antibodies against H. pylori and CagA protein. Infection by the virulent strain was found in 82% (40/55 of the patients, and among these, 89% (40/45 presented an increased degree of inflammation in the gastric mucosa, with a dense infiltration of leukocytes in the tissue, which probably favored the formation of gastric ulcer. We concluded that the presence of the virulent strain is related to the development of an increased inflammation in the gastric mucosa.

Development of gastric cancer associated with Helicobacter pylori infection.

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Sugiyama, Toshiro

2004-09-01

Helicobacter pylori infection is associated with histological gastritis, gastric atrophy, gastric cancer and mucosa-associated lymphoid tissue lymphoma in the stomach. However, gastric cancer only develops in a minority of infected individuals. Such clinical diversity is caused by variations in the interactions between H. pylori pathogenicity, host susceptibility, and environmental factors. Based on evidence from three prospective epidemiological studies, the International Agency for Research on Cancer and the World Health Organization (IARC/WHO) concluded in 1994 that H. pylori has a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. Two large-scale, prospective, epidemiological studies have recently been reported in Japan and have confirmed that H. pylori infection constitutes a high risk factor for the development of gastric cancer, at least in males. In order to obtain evidence that eradication of H. pylori leads to a reduction in the occurrence of gastric cancer, reversibility of precancerous lesions, gastric atrophy or intestinal metaplasia should be proven after eradication treatment. A biopsy specimen from the lesser curvature of the corpus is the most sensitive for evaluating the regression of gastric atrophy on histology, and the evaluation needs be conducted at least 13 months after treatment. In a Mongolian gerbil model with or without low-dose chemical carcinogens, it has been demonstrated that H. pylori can lead to the development of gastric cancer. Experimental studies have elucidated that virulence factors of H. pylori interact with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster; it encodes the type IV secretion machinery system forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird phenotype, a growth factor-like effect. The other gene products are

The Middle Fragment of Helicobacter pylori CagA Induces Actin Rearrangement and Triggers Its Own Uptake into Gastric Epithelial Cells

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Abolghasem Tohidpour

2017-07-01

Full Text Available Cytotoxin-associated gene product A (CagA is a major virulence factor secreted by Helicobacter pylori. CagA activity in the gastric epithelium is associated with higher risk of gastric cancer development. Bacterial type IV secretion system (T4SS-mediated translocation of CagA into the cytosol of human epithelial cells occurs via a poorly understood mechanism that requires CagA interaction with the host membrane lipid phosphatidylserine (PS and host cell receptor integrin α5β1. Here we have characterized the isolated recombinant middle fragment of CagA (CagA-M that contains the positively-charged PS-binding region (aa 613–636 and a putative β1 integrin binding site, but lacks the EPIYA region, secretion signal peptide and the CagA multimerization motif. We show that CagA-M, when immobilized on latex beads, is capable of binding to, and triggering its own uptake into, gastric epithelial cells in the absence of infection with cagA-positive H. pylori. Using site-directed mutagenesis, fluorescent and electron microscopy, and highly-specific inhibitors, we demonstrate that the cell-binding and endocytosis-like internalization of CagA-M are dependent on (1 binding to PS; (2 β1 integrin activity; and (3 actin dynamics. Interaction of CagA-M with the host cells is accompanied by the development of long filopodia-like protrusions (macrospikes. This novel morphology is different from the hummingbird phenotype induced by the translocation of full-length CagA. The determinants within CagA-M and within the host that are important for endocytosis-like internalization into host cells are very similar to those observed for T4SS-mediated internalization of full-length CagA, suggesting that the latter may involve an endocytic pathway.

The distribution of cagA and dupA genes in Helicobacter pylori strains in Kurdistan region, northern Iraq.

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Salih, Azad M; Goreal, Amer; Hussein, Nawfal R; Abdullah, Shahla M; Hawrami, Khidir; Assafi, Mahde

2013-01-01

Helicobacter pylori is a Gram negative bacteria that causes peptic ulceration and gastric adenocarcinoma. H pylori virulence factors, such as cagA and dupA, are important to study in populations as they contribute to disease risk. This study aimed to look at the distribution of the cagA and dupA genes in H pylori strains isolated from patients suffering from gastroduodenal diseases in Kurdistan region, Iraq. A cross-sectional study conducted between June 2011 and January 2012. Biopsies were collected from the Endoscopy Department in Duhok and Sulaimania hospitals, Kurdistan region, northern Iraq. Upper gastrointestinal (GI) endoscopy examination was performed and 4 gastric biopsies (2 from the antrum and 2 from the corpus) were obtained from 204 patients. H pylori positivity was examined by CLO test; then the association between disease status and virulence factors was assessed by polymerase chain reaction. 154 (75%) of our samples were found to be H pylori + by CLO test. Endoscopic diagnoses for those who were positive were as follows: peptic ulcer disease (PUD) including duodenal ulcer, 45; gastric ulcer, 23; and no ulcer (NPUD), 86. The overall prevalence rates of cagA and dupA were 72.7% and 18.8%, respectively. While a significant association between cagA and PUD was observed (P. ≤.017; OR=0.4; CI=0.18–0.85), no relationship between dupA and PUD could be seen. These data suggested that the presence of cagA may be a predictor of clinical outcome in Kurdistan region, northern Iraq.

Anti-CagA positivity in duodenal ulcer and functional dyspepsia patients infected with Helicobacter pylori and its effect on the outcome of eradication treatment

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Yaşar Nazlıgül

2011-03-01

Full Text Available Objectives: CagA positive H. pylori strains are considered to be more virulent than other strains. In this study, we aimed to investigate the rate of CagA positivity in duodenal ulcer (DU and functional dyspepsia (FD, and its effect on H. pylori eradication response.Materials and methods: The study was performed on H. pylori positive 60 patients with DU and 50 patients with FD, who underwent upper gastrointestinal endoscopy. H. pylori infection was identified by histology. All patients received a quadriple therapy consisted of esomeprazole 20 mg b.i.d., colloidal bismuth subcitrate 600 mg b.i.d., tetracycline 500 mg q.i.d. and metronidazole 500 mg t.i.d. for 7 days. H.pylori status was rechecked using C14-urea breath test 6 weeks after the end of treatment to confirm cure. Specific IgG antibodies for CagA status were determined by enzyme linked immunosorbent assay.Results: CagA positivities in the patients with DU and FD were calculated respectivily 70% and 68% (P>0.05. H. pylori was eradicated in 85.5% of the patients infected with CagA (+ strains, in 50% of those infected with CagA (- strains (P=0.001. The eradication rates were 95.2% and 55.6% in CagA positive and negative DU subgroups (P=0.001, and 73.5% and 43.8% in CagA positive and negative FD subgroups (P=0.04.Conclusion: CagA positivities were not different in duodenal ulcer and functional dyspepsia. CagA (+ strains was susceptible to the eradication treatment. The titres of serum anti-CagA antibodies may be used in the prediction of eradication outcome, and the modification of eradication therapy.

Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

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Meyssa Quezado de Figueiredo Cavalcante

2012-06-01

Full Text Available Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR = 5.72, 95% confidence interval (CI = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31. Patients with gastric cancer (21/21, 100%, p = 0.006 or peptic ulcers (20/21, 95%, p = 0.02 were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%. In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.

CagA and VacA Helicobacter Pylori Antibodies in Gastric Cancer

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Renzo Suriani

2008-01-01

Full Text Available BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]-and/or vacuolating cytotoxin A [VacA]-positive can play a role in the development of atrophic gastritis, duodenal ulcer (DU and gastric cancer (GC.

A study of RUNX3, E-cadherin and β-catenin in CagA-positive Helicobacter pylori associated chronic gastritis in Saudi patients.

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Wagih, H M; El-Ageery, S M; Alghaithy, A A

2015-04-01

H. pylori is the most important risk factor for gastric carcinoma. CagA-positive H. pylori is associated with an increased risk for gastric cancer compared with negative strains. RUNX3 is a tumor suppressor gene, which is related to the genesis of gastric cancer. β-catenin is integrated with E-cadherin in the cell membrane, and aberrant expression of the complex was reported in gastric carcinoma. Aim of this paper is to determine of the relation between RUNX3, E-cadherin and β-catenin in chronic gastritis associated with cagA-positive H. pylori infection. Retrospective study was done on formalin fixed paraffin embedded gastric biopsies blocks of 90 patients diagnosed as H. pylori associated chronic gastritis. H. pylori was detected using modified Giemsa stain. Nested PCR was used for detection of cagA, reverse transcription-PCR for detection of RUNX3 and immunohistochemistry for detection of E-cadherin and β-catenin. Fifty percent of cases were found to be cagA positive. CagA was significantly associated with the intensity of mononuclear inflammation, the intensity of neutrophilic inflammation, the degree of mucosal atrophy and loss of RUNX3 but not with the density of H. pylori, intestinal metaplasia, E-cadherin or β-catenin. There was significant relation between loss of RUNX3 and increasing density of H. pylori, intensity of neutrophilic inflammation, mucosal atrophy and intestinal metaplasia. RUNX3 was found to be significantly correlated with E-cadherin but not with β-catenin. E-cadherin showed decreased expression in 36.7% of biopsies while, β-catenin was decreased in 33% of biopsies. Loss of RUNX3, E-cadherin and β-catenin was considered early events in the cascade of gastric carcinoma development. Loss of RUNX3 but neither E-cadherin nor β-catenin was related to cagA positive H. pylori strains.

Higher frequency of cagA EPIYA-C Phosphorylation Sites in H. pylori strains from first-degree relatives of gastric cancer patients

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Queiroz Dulciene MM

2012-08-01

Full Text Available Abstract Background To evaluate the prevalence of more virulent H. pylori genotypes in relatives of gastric cancer patients and in patients without family histories of gastric cancer. Methods We evaluated prospectively the prevalence of the infection by more virulent H. pylori strains in 60 relatives of gastric cancer patients comparing the results with those obtained from 49 patients without family histories of gastric cancer. H. pylori status was determined by the urease test, histology and presence of H. pylori ureA. The cytotoxin associated gene (cagA, the cagA-EPIYA and vacuolating cytotoxin gene (vacA were typed by PCR and the cagA EPIYA typing was confirmed by sequencing. Results The gastric cancer relatives were significant and independently more frequently colonized by H. pylori strains with higher numbers of CagA-EPIYA-C segments (OR = 4.23, 95%CI = 1.53–11.69 and with the most virulent s1m1 vacA genotype (OR = 2.80, 95%CI = 1.04–7.51. Higher numbers of EPIYA-C segments were associated with increased gastric corpus inflammation, foveolar hyperplasia and atrophy. Infection by s1m1 vacA genotype was associated with increased antral and corpus gastritis. Conclusions We demonstrated that relatives of gastric cancer patients are more frequently colonized by the most virulent H. pylori cagA and vacA genotypes, which may contribute to increase the risk of gastric cancer.

VacA, CagA, IceA and OipA Genotype Status of Helicobacter pylori ...

African Journals Online (AJOL)

Purpose: To investigate the state of vacA, cagA, oipA and iceA genotypes of H. pylori isolated from gastric biopsy samples of dogs. Methods: A total of 240 gastric biopsy samples were taken from 240 dogs using gastric endoscope. All the samples were cultured and H. pylori-positive samples were analyzed for the presence ...

Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains.

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Judith Lind

Full Text Available The clinical outcome of Helicobacter pylori infections is determined by multiple host-pathogen interactions that may develop to chronic gastritis, and sometimes peptic ulcers or gastric cancer. Highly virulent strains encode a type IV secretion system (T4SS that delivers the effector protein CagA into gastric epithelial cells. Translocated CagA undergoes tyrosine phosphorylation at EPIYA-sequence motifs, called A, B and C in Western-type strains, by members of the oncogenic Src and Abl host kinases. Phosphorylated EPIYA-motifs mediate interactions of CagA with host signaling factors--in particular various SH2-domain containing human proteins--thereby hijacking multiple downstream signaling cascades. Observations of tyrosine-phosphorylated CagA are mainly based on the use of commercial phosphotyrosine antibodies, which originally were selected to detect phosphotyrosines in mammalian proteins. Systematic studies of phosphorylated EPIYA-motif detection by the different antibodies would be very useful, but are not yet available. To address this issue, we synthesized phospho- and non-phosphopeptides representing each predominant Western CagA EPIYA-motif, and determined the recognition patterns of seven different phosphotyrosine antibodies in Western blots, and also performed infection studies with diverse representative Western H. pylori strains. Our results show that a total of 9-11 amino acids containing the phosphorylated EPIYA-motifs are necessary and sufficient for specific detection by these antibodies, but revealed great variability in sequence recognition. Three of the antibodies recognized phosphorylated EPIYA-motifs A, B and C similarly well; whereas preferential binding to phosphorylated motif A and motifs A and C was found with two and one antibodies, respectively, and the seventh anti-phosphotyrosine antibody did not recognize any phosphorylated EPIYA-motif. Controls showed that none of the antibodies recognized the corresponding non

Immunopathological and Modulatory Effects of Cag A+ Genotype on Gastric Mucosa, Inflammatory Response, Pepsinogens, and Gastrin-17 Secretion in Iraqi Patients infected with H. pylori.

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Al-Ezzy, Ali Ibrahim Ali

2018-05-20

significant difference was reported in lymphocyte grades among different disorders according to H. pylori IgG. A significant difference was reported in serum level of PG I; PG II; PG I/PG II; G-17 according to PMN and lymphocyte grades (P-value ˂ 0.01). PMNs grades positively correlated with gastric Cag A expression; H. pylori IgG; PG II; G-17 levels. PG I; PG I/ PG II correlated with lymphocyte grades (P-value ˂ 0.05); while PGII has a negative correlation (P-value = 0.039). Endoscopic mucosal finding does not reflect exactly the actual immunopathological changes of gastric mucosa during H. pylori infection. Secretion of gastrin was not affected by the presence of Cag A in gastric tissue. Instead, the fluctuation in the hormone level appears to be due to the presence of H. pylori infection in gastric tissue. Gastric tissue infiltration with PMNs & lymphocytes inflammatory infiltrates has a direct effect on PGs and gastrin levels in serum of infected patients. The level of PG I; PG II; G-17 secretion correlated with the development of immune response against H. pylori and production of specific H. pylori IgG. Finally, H. pylori can modulate gastric secretions through Cag A dependent and independent pathways.

The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population.

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Beltrán-Anaya, Fredy Omar; Poblete, Tomás Manuel; Román-Román, Adolfo; Reyes, Salomón; de Sampedro, José; Peralta-Zaragoza, Oscar; Rodríguez, Miguel Ángel; del Moral-Hernández, Oscar; Illades-Aguiar, Berenice; Fernández-Tilapa, Gloria

2014-12-24

Helicobacter pylori chronic infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. Cytotoxin-associated gene A (cagA)-positive H. pylori strains increase the risk of gastric pathology. The carcinogenic potential of CagA is linked to its polymorphic EPIYA motif variants. The goals of this study were to investigate the frequency of cagA-positive Helicobacter pylori in Mexican patients with gastric pathologies and to assess the association of cagA EPIYA motif patterns with peptic ulcer and gastric cancer. A total of 499 patients were studied; of these, 402 had chronic gastritis, 77 had peptic ulcer, and 20 had gastric cancer. H. pylori DNA, cagA, and the EPIYA motifs were detected in total DNA from gastric biopsies by PCR. The type and number of EPIYA segments were determined by the electrophoretic patterns. To confirm the PCR results, 20 amplicons of the cagA 3' variable region were sequenced, and analyzed in silico, and the amino acid sequence was predicted with MEGA software, version 5. The odds ratio (OR) was calculated to determine the associations between the EPIYA motif type and gastric pathology and between the number of EPIYA-C segments and peptic ulcers and gastric cancer. H. pylori DNA was found in 287 (57.5%) of the 499 patients, and 214 (74%) of these patients were cagA-positive. The frequency of cagA-positive H. pylori was 74.6% (164/220) in chronic gastritis patients, 73.6% (39/53) in peptic ulcer patients, and 78.6% (11/14) in gastric cancer patients. The EPIYA-ABC pattern was more frequently observed in chronic gastritis patients (79.3%, 130/164), while the EPIYA-ABCC sequence was more frequently observed in peptic ulcer (64.1%, 25/39) and gastric cancer patients (54.5%, 6/11). However, the risks of peptic ulcer (OR = 7.0, 95% CI = 3.3-15.1; p peptic ulcers and gastric cancer.

Prevalence of Helicobacter pylori cagA, babA2, and dupA genotypes andcorrelation with clinical outcome in Malaysian patients with dyspepsia

OpenAIRE

OSMAN, HUSSEIN ALI; HASAN, HABSAH; SUPPIAN, RAPEAH; HASSAN, SYED; ANDEE, DZULKARNAEN ZAKARIA; MAJID, NOORIZAN ABDUL; ZILFALIL, BIN ALWI

2015-01-01

Background/aim: The severity of disease outcome in dyspepsia has been attributed to Helicobacter pylori virulence genes. The aim of this study was to determine the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to determine whether or not there arises a significant correlation with clinical dyspepsia outcomes. Materials and methods: H. pylori genotypes cagA, babA2, and dupA were identified by polymerase chain reactions from gastric biopsy samples in 105 H. pylori-posit...

Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment

NARCIS (Netherlands)

L.-J. van Doorn (Leen-Jan); P.M. Schneeberger (Peter); N. Nouhan (N.); A.P. Plaisier (Anton); W.G.V. Quint (Wim); W.A. de Boer (Wink)

2000-01-01

textabstractBackground - Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment. Aims - To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome. Patients -

Analysis of clinical isolates of Helicobacter pylori in Pakistan reveals high degrees of pathogenicity and high frequencies of antibiotic resistance.

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Rasheed, Faisal; Campbell, Barry James; Alfizah, Hanafiah; Varro, Andrea; Zahra, Rabaab; Yamaoka, Yoshio; Pritchard, David Mark

2014-10-01

Antibiotic resistance in Helicobacter pylori contributes to failure in eradicating the infection and is most often due to point and missense mutations in a few key genes. The antibiotic susceptibility profiles of H. pylori isolates from 46 Pakistani patients were determined by Etest. Resistance and pathogenicity genes were amplified, and sequences were analyzed to determine the presence of mutations. A high percentage of isolates (73.9%) were resistant to metronidazole (MTZ), with considerable resistance to clarithromycin (CLR; 47.8%) and amoxicillin (AML; 54.3%) also observed. Relatively few isolates were resistant to tetracycline (TET; 4.3%) or to ciprofloxacin (CIP; 13%). However, most isolates (n = 43) exhibited resistance to one or more antibiotics. MTZ-resistant isolates contained missense mutations in oxygen-independent NADPH nitroreductase (RdxA; 8 mutations found) and NADH flavin oxidoreductase (FrxA; 4 mutations found). In the 23S rRNA gene, responsible for CLR resistance, a new point mutation (A2181G) and 4 previously reported mutations were identified. Pathogenicity genes cagA, dupA, and vacA s1a/m1 were detected frequently in isolates which were also found to be resistant to MTZ, CLR, and AML. A high percentage of CagA and VacA seropositivity was also observed in these patients. Phylogenetic analysis of partial sequences showed uniform distribution of the 3' region of cagA throughout the tree. We have identified H. pylori isolates in Pakistan which harbor pathogenicity genes and worrying antibiotic resistance profiles as a result of having acquired multiple point and missense mutations. H. pylori eradication regimens should therefore be reevaluated in this setting. © 2014 John Wiley & Sons Ltd.

Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by mononuclear cells.

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Hussein, Nawfal R; Argent, Richard H; Marx, Christian K; Patel, Sapna R; Robinson, Karen; Atherton, John C

2010-07-15

Infection with Helicobacter pylori possessing a newly described virulence factor--duodenal ulcer-promoting gene A (dupA)--has been associated with duodenal ulceration and increased gastric inflammation. The dupA locus of 34 strains was sequenced. A panel of dupA mutants was generated and cocultured with human gastric epithelial cells and peripheral blood mononuclear cells; proinflammatory cytokine release was measured. IL8 expression was measured in human gastric biopsy specimens and related to the dupA and cagA status of infecting strains. Most H. pylori strains had a dupA allele that was longer (1884 bp; dupA1) than previously described dupA alleles, although some had truncated versions (dupA2). Unlike the best-characterized H. pylori virulence determinant, the cag pathogenicity island (cag PaI), neither dupA type induced release of interleukin (IL)-8 from gastric epithelial cells. However, infections due to dupA-positive strains were associated with higher-level mucosal IL-8 messenger RNA expression in the human stomach than were infections due to dupA-negative strains. To explain this paradox, we found that dupA1 (but not dupA2 or the cag PaI) substantially increased H. pylori-induced IL-12p40 and IL-12p70 production from CD14(+) mononuclear cells. Other T helper 1-associated cytokines were also modestly induced. We suggest that virulent H. pylori strains cause inflammation by stimulating epithelial cells through cag-encoded proteins and mononuclear inflammatory cells through dupA1 products.

VacA and cagA genotypes of Helicobacter pylori isolated from raw meat in Isfahan province, Iran.

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Gilani, Ali; Razavilar, Vadood; Rokni, Nordahr; Rahimi, Ebrahim

2017-01-01

Foods with animal origins play a substantial role in the transmission of Helicobacter pylori . The present investigation was carried out to study the vacA and cagA genotypes status of H. pylori isolated from various types of meat samples. Two hundred and twenty meat samples were collected and cultured. H. pylori -positive strains were analyzed for the presence of vacA and cagA genotypes. Eleven out of 220 (5.00%) samples were positive for H. pylori . Findings were confirmed by nested PCR. Prevalence of H. pylori in the meat samples of slaughterhouses and butcheries were 72.20% and 27.70%, respectively. The most commonly detected genotypes in the meat samples of slaughterhouses and butcheries were vacA m1a (66.66%) and vacA s1a (37.50%), respectively. The S1am1a was the most commonly detected genotype. Meat sampled from butcheries had the higher prevalence of H. pylori and its genotypes than those of slaughterhouses ( p meat samples could be the potential sources of virulent strains of H. pylori . Application of sanitary measures in the storage, transportation and sale of meat is essential for reducing the levels of H. pylori cross contamination.

Distribution of Helicobacter pylori cagA, cagE and vacA in different ethnic groups in Kuala Lumpur, Malaysia.

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Tan, Huck Joo; Rizal, Abdul Manaf; Rosmadi, Mohamed-Yusoff; Goh, Khean-Lee

2005-04-01

There is a geographic variation in Helicobacter pylori (HP) genotypes and virulence factors. Cytotoxin associated genes A (cagA) and E (cagE), and certain vacuolating cytotoxin (vacA) genotypes are associated with peptic ulcer disease (PUD). There is also a different prevalence of PUD among different ethnic groups in Malaysia. The present study compared the distribution of vacA alleles and cagA and cagE status in three ethnic groups residing in Kuala Lumpur, Malaysia, and their association with clinical outcome. All patients with cultured positive HP were recruited prospectively. DNA was extracted and polymerase chain reaction was carried out to determine the cagA and cagE status and vacA alleles. The results of 127 patients (72 men and 55 women) were included. The mean age was 55.53 +/- 12.52 years. The ethnic distribution was 59 Chinese, 38 Indian and 30 Malay patients. The predominant genotype was s1a among the Malay (76.6%) and Indian patients (71.0%), and s1c among the Chinese patients (66.1%). The vacA middle region sequence m1 was detected in 66.7% of Malay, 54.2% of Chinese and 76.3% of Indian patients. Of the Malay, Chinese and Indian patients, 76.6%, 86.4% and 86.8%, respectively, were cagA positive, and 70.0%, 39.0% and 81.6%, respectively, were cagE positve. HP cagA, cagE and vacA were not associated with PUD. There is a distinctive difference in the HP strains among the three ethnic groups in Malaysia. There was no association between cagA, cagE or vacA genotypes and clinical outcome in the patients. None of these markers are helpful in predicting the clinical presentation of a HP infection.

Relationship between New Allelic Types of Helicobacter pylori vacA Gene and cagA Status and Risk of GU or DU in Iran

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S Bakhti

2015-09-01

Full Text Available Background & objectives: Several studies have described VacA and CagA as the two important virulence determinants of Helicobacter pylori, which are associated with gastric ulcer (GU and duodenal ulcer (DU. The aim of present study was to determine the associations of the i and d regions genotypes of H. pylori vacA gene and cagA status with GU and DU risk. Methods: A total of 177 isolates were cultured from the biopsies of Iranian patients with different geographic origins and genotyped. Data were collected and analyzed. Results: Frequency of the vacA i1, i2, i1i2, d1, and d2 alleles and cagA in all patients was 42.9%, 55.4%, 1.7%, 41.8%, 58.2% and 68.4%, respectively. There was a significant difference between the frequencies of vacA i1 in isolates from GU than those from non-atrophic gastritis (p<0.05. When the GU was considered as a dependant factor by the multiple logistic regression analysis, the vacA i1 genotype was significantly associated with the age- and sex-adjusted risk for GU (p=0.006, odds ratio [OR]=3.56 95% confidence interval [CI]=1.45–8.75. Statistical analysis showed no significant association between vacA d genotype and digestive diseases. After controlling for age and sex variables, the cagA genotype remained in the final model when the DU was considered as a dependant factor by the the multiple logistic regression analysis (p=0.021, OR=3.77 95% CI=1.22-11.60. Conclusion: We have proposed that the H. pylori vacA i1 and cagA genotypes could be considered as benefit biomarkers for prediction of risk of GU and DU in Iran, respectively.

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

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Pereira, Weendelly Nayara; Ferraz, Mariane Avante; Zabaglia, Luanna Munhoz; de Labio, Roger William; Orcini, Wilson Aparecido; Bianchi Ximenez, João Paulo; Neto, Agostinho Caleman; Payão, Spencer Luiz Marques; Rasmussen, Lucas Trevizani

2014-01-23

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. 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. 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.

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention Helicobacter pylori: avances recientes en el estudio de su prevención y patogenicidad

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Germán R. Aguilar

2001-06-01

Full Text Available Helicobacter pylori has acquired great importance during the last two decades, after being recognized as an important pathogen that infects a great portion of the human population. This microorganism is recognized as the main causal agent of chronic gastritis and duodenal ulcers, and it is associated with the subsequent development of gastric carcinoma. The pathogenic mechanisms of H. pylori and their relation to gastric ailments have not been clearly defined. However, at present it is well established that urease, vacuolating cytotoxin VacA, and the pathogenicity island (cag PAI gene products, are the main factors of virulence of this organism. Thus, individuals infected with strains that express these virulence factors probably develop a severe local inflammation that may induce the development of peptic ulcer and gastric cancer. The way the infection spreads throughout the world suggests the possibility that there are multiple pathways of transmission. Due to the importance that H. pylori has acquired as a human pathogen, laboratories worldwide are attempting to develop a vaccine that confers long-term immunological protection against infection by this microorganism. Hence, the objective of this review is to present the most relevant findings of the biology of H. Pylori and its interaction with the human host. The full version of this paper is available too at: http://www.insp.mx/salud/index.htmlHelicobacter pylori ha adquirido gran importancia durante las últimas dos décadas, al ser reconocido como un importante patógeno que infecta una gran porción de la población humana. Este microrganismo es reconocido como el principal agente que causa la gastritis crónica y la úlcera duodenal, además de que se ha asociado con el subsecuente desarrollo del carcinoma gástrico. Los mecanismos patogénicos de H. pylori y su relación con los padecimientos gástricos no se han definido en forma clara. Sin embargo, actualmente está bien establecido

Helicobacter pylori Type IV Secretion System and Its Adhesin Subunit, CagL, Mediate Potent Inflammatory Responses in Primary Human Endothelial Cells

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Mona Tafreshi

2018-02-01

Full Text Available The Gram-negative bacterium, Helicobacter pylori, causes chronic gastritis, peptic ulcers, and gastric cancer in humans. Although the gastric epithelium is the primary site of H. pylori colonization, H. pylori can gain access to deeper tissues. Concurring with this notion, H. pylori has been found in the vicinity of endothelial cells in gastric submucosa. Endothelial cells play crucial roles in innate immune response, wound healing and tumorigenesis. This study examines the molecular mechanisms by which H. pylori interacts with and triggers inflammatory responses in endothelial cells. We observed that H. pylori infection of primary human endothelial cells stimulated secretion of the key inflammatory cytokines, interleukin-6 (IL-6 and interleukin-8 (IL-8. In particular, IL-8, a potent chemokine and angiogenic factor, was secreted by H. pylori-infected endothelial cells to levels ~10- to 20-fold higher than that typically observed in H. pylori-infected gastric epithelial cells. These inflammatory responses were triggered by the H. pylori type IV secretion system (T4SS and the T4SS-associated adhesin CagL, but not the translocation substrate CagA. Moreover, in contrast to integrin α5β1 playing an essential role in IL-8 induction by H. pylori upon infection of gastric epithelial cells, both integrin α5β1 and integrin αvβ3 were dispensable for IL-8 induction in H. pylori-infected endothelial cells. However, epidermal growth factor receptor (EGFR is crucial for mediating the potent H. pylori-induced IL-8 response in endothelial cells. This study reveals a novel mechanism by which the H. pylori T4SS and its adhesin subunit, CagL, may contribute to H. pylori pathogenesis by stimulating the endothelial innate immune responses, while highlighting EGFR as a potential therapeutic target for controlling H. pylori-induced inflammation.

Frecuencia de los genotipos babA2, oipA y cagE de Helicobacter pylori en pacientes colombianos con enfermedades gastroduodenales.

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Andrés Javier Quiroga

2005-09-01

Full Text Available Introducción. La infección con Helicobacter pylori está asociada con el desarrollo de diferentes enfermedades gastroduodenales. Varios genes de virulencia de H. pylori se han relacionado con mayor riesgo de enfermedad gástrica. Objetivos. El propósito de este trabajo fue determinar las posibles asociaciones entre la presencia de los genes vacA, cagA, cagE, babA2 y oipA en aislamientos de H. pylori de pacientes colombianos y las diferentes consecuencias clínicas de la infección. Materiales y métodos. Mediante PCR se evaluaron los genotipos cagA, vacA, cagE, oipA y babA2 en 166 aislamientos de H. pylori provenientes de 50 pacientes con úlcera péptica, 39 con gastritis crónica no atrófica, 26 con gastritis crónica atrófica, 26 con metaplasia intestinal y 25 con adenocarcinoma gástrico. Resultados. La frecuencia de los genotipos cagA, cagE, babA2 y oipA fue de 73%, 75%, 48% y 74%, respectivamente. El 64% (100/157 de los aislamientos presentó el genotipo citotóxico vacAs1m1/cagA positivo/cagE positivo. Se observó una mayor frecuencia de cepas citotóxicas en pacientes con cáncer (84%, metaplasia (91% y úlcera (81% en comparación con pacientes con gastritis no atrófica (50% (p=0,002, 0,008 y 0,007, respectivamente. La frecuencia de oipA y babA2 fue mayor en cepas citotóxicas que en cepas no citotóxicas (oipA: 81% vs. 52%, p=0,003; babA2: 58% vs. 12%, p=0,000. No se observaron diferencias significativas en la frecuencia de los genes oipA o babA2 solos o en asociación con vacA y cagA/cagE y las diferentes enfermedades gastroduodenales. Conclusiones. No se encontraron evidencias que sugieran que los genes babA2 u oipA puedan servir como marcadores de ulcerogénesis o carcinogénesis en esta población, solos o en asociación con cagA, cagE o vacA.

Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis

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Sahara Shu

2012-09-01

Full Text Available Abstract Background Infection with cagA-positive, cagA EPIYA motif ABD type, and vacA s1, m1, and i1 genotype strains of Helicobacter pylori is associated with an exacerbated inflammatory response and increased risk of gastroduodenal diseases. However, it is unclear whether the prevalence and virulence factor genotypes found in Southeast Asia are similar to those in Western countries. Here, we examined the cagA status and prevalence of cagA EPIYA motifs and vacA genotypes among H. pylori strains found in Southeast Asia and examined their association with gastroduodenal disease. Methods To determine the cagA status, cagA EPIYA motifs, and vacA genotypes of H. pylori, we conducted meta-analyses of 13 previous reports for 1,281 H. pylori strains detected from several Southeast Asian countries. Results The respective frequencies of cagA-positive and vacA s1, m1, and i1 genotypes among examined subjects were 93% (1,056/1,133, 98% (1,010/1,033, 58% (581/1,009, and 96% (248/259, respectively. Stratification showed significant variation in the frequencies of cagA status and vacA genotypes among countries and the individual races residing within each respective country. The frequency of the vacA m-region genotype in patients infected with East Asian-type strains differed significantly between the northern and southern areas of Vietnam (p vacA m1 type or cagA-positive strains was associated with an increased risk of peptic ulcer disease (odds ratio: 1.46, 95%CI: 1.01-2.12, p = 0.046 and 2.83, 1.50-5.34, p = 0.001, respectively in the examined Southeast Asian populations. Conclusions Both Western- and East Asian-type strains of H. pylori are found in Southeast Asia and are predominantly cagA-positive and vacA s1 type. In Southeast Asia, patients infected with vacA m1 type or cagA-positive strains have an increased risk of peptic ulcer disease. Thus, testing for this genotype and the presence of cagA may have clinical usefulness.

Características da gastrite crônica associada a Helicobacter pylori: aspectos topográficos, doenças associadas e correlação com o status cagA Helicobacter pylori associated gastritis: topographical pattern, associated diseases and correlation with cagA status

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Mônica Maria Demas Álvares

2006-02-01

Full Text Available OBJETIVOS: Analisar o padrão topográfico da gastrite por H. pylori em relação ao status cagA e associação com úlcera duodenal (UD e carcinoma gástrico precoce (CaGp. MATERIAL E MÉTODO: Estudamos prospectivamente 160 biopsias endoscópicas e 40 peças de gastrectomia por CaGp. Amostras do antro e do corpo na pequena e grande curvaturas, da incisura e do tumor, foram processadas rotineiramente para histologia com histoquímica para caracterização da metaplasia intestinal (MI. O Helicobacter pylori foi avaliado por histologia, imuno-histoquímica, cultura e reação em cadeia de polimerase (PCR e o status cagA por PCR. A gastrite crônica (GC foi classificada segundo o sistema Sydney. Realizou-se estudo topográfico em 130 pacientes, analisando os parâmetros de gastrite comparativamente entre as áreas e em relação ao status cagA. RESULTADOS: Cento e vinte e um pacientes apresentaram GC, 24 UD e 14 eram normais. Detectaram-se amostras cagA-positivas em 59 pacientes com GC, 17 com UD e 24 com CaGp. Todos os parâmetros de GC foram significativamente mais intensos nos pacientes infectados por amostras cagA-positivas, que se associavam ainda à presença de atrofia e MI. A MI foi significativamente mais intensa na porção média da pequena curvatura antral do que nas demais regiões. Nos pacientes com GC e CaGp, infectados por amostras cagA-positivas, inflamação e atividade acometiam igualmente o antro e corpo distal, enquanto a atrofia e a MI predominavam no antro, particularmente na pequena curvatura do antro médio. Nos pacientes cagA-negativos a GC era predominantemente antral, e na UD a GC apresentava predominância antral, independentemente do status cagA. CONCLUSÕES: Nossos dados sugerem que o padrão de gastrite por H. pylori se relaciona com fatores de virulência da bactéria. As lesões pré-neoplásicas são significativamente mais intensas na pequena curvatura do antro médio, onde surge a maioria dos carcinomas g

cagA Status and Eradication Treatment Outcome of Anti-Helicobacter pylori Triple Therapies in Patients with Nonulcer Dyspepsia

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Broutet, Nathalie; Marais, Armelle; Lamouliatte, Hervé; de Mascarel, Antoine; Samoyeau, Roland; Salamon, Roger; Mégraud, Francis

2001-01-01

The differences in eradication rates reported in clinical trials aiming to cure Helicobacter pylori infection cannot be entirely explained by the type of regimen, bacterial resistance, or lack of compliance. Using data from a clinical trial, a logistic regression model was constructed to determine whether cagA status, assessed by PCR, affects the outcome of eradication. Resistance to clarithromycin (10% of the strains) predicted failure perfectly. In the model (n = 156), a cagA-lacking strain (odds ratio [OR] = 2.2; 95% confidence interval [CI], (1.1 to 4.7), tobacco smoking OR = 3.1; 95% CI, 1.3 to 7.0), and a double dose of proton pump inhibitor in the treatment regimen (OR = 0.3; 95% CI, 0.2 to 0.7) were associated with the treatment outcome. The exact role of cagA in the outcome of H. pylori eradication therapy has not been explored. However, the type of histological lesions which it causes in the gastric mucosa may be implicated. Regardless of the mechanism involved, cagA status is a good predictive marker of eradication outcome. PMID:11283049

Helicobacter pylori genotyping from positive clotests in patients with duodenal ulcer

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Mattar Rejane

2000-01-01

Full Text Available Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5%; only two (5% patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5% patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.

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

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

2017-09-01

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 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.

Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates

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Mendonça Sergio

2003-08-01

Full Text Available Abstract Background In this study, we evaluated the prevalence of primary resistance of Brazilian H. pylori isolates to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone. In addition, the vacA, iceA, cagA and cagE genotypes of strains isolated from Brazilian patients were determined and associated with clinical data in an effort to correlate these four virulence markers and antibiotic resistance. Methods H. pylori was cultured in 155 H. pylori-positive patients and MICs for metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone were determined by the agar dilution method. Genomic DNA was extracted, and allelic variants of vacA, iceA, cagA and cagE were identified by the polymerase chain reaction. Results There was a strong association between the vacA s1/cagA -positive genotype and peptic ulcer disease (OR = 5.42, 95% CI 2.6–11.3, p = 0.0006. Additionally, infection by more virulent strains may protect against GERD, since logistic regression showed a negative association between the more virulent strain, vacA s1/cagA-positive genotype and GERD (OR = 0.26, 95% CI 0.08–0.8, p = 0.03. Resistance to metronidazole was detected in 75 patients (55%, to amoxicillin in 54 individuals (38%, to clarithromycin in 23 patients (16%, to tetracycline in 13 patients (9%, and to furazolidone in 19 individuals (13%. No significant correlation between pathogenicity and resistance or susceptibility was detected when MIC values for each antibiotic were compared with different vacA, iceA, cagA and cagE genotypes. Conclusion The analysis of virulence genes revealed a specific association between H. pylori strains and clinical outcome, furthermore, no significant association was detected among pathogenicity and resistance or susceptibility.

Distinct repeat motifs at the C-terminal region of CagA of Helicobacter pylori strains isolated from diseased patients and asymptomatic individuals in West Bengal, India

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Chattopadhyay Santanu

2012-05-01

Full Text Available Abstract Background Infection with Helicobacter pylori strains that express CagA is associated with gastritis, peptic ulcer disease, and gastric adenocarcinoma. The biological function of CagA depends on tyrosine phosphorylation by a cellular kinase. The phosphate acceptor tyrosine moiety is present within the EPIYA motif at the C-terminal region of the protein. This region is highly polymorphic due to variations in the number of EPIYA motifs and the polymorphism found in spacer regions among EPIYA motifs. The aim of this study was to analyze the polymorphism at the C-terminal end of CagA and to evaluate its association with the clinical status of the host in West Bengal, India. Results Seventy-seven H. pylori strains isolated from patients with various clinical statuses were used to characterize the C-ternimal polymorphic region of CagA. Our analysis showed that there is no correlation between the previously described CagA types and various disease outcomes in Indian context. Further analyses of different CagA structures revealed that the repeat units in the spacer sequences within the EPIYA motifs are actually more discrete than the previously proposed models of CagA variants. Conclusion Our analyses suggest that EPIYA motifs as well as the spacer sequence units are present as distinct insertions and deletions, which possibly have arisen from extensive recombination events. Moreover, we have identified several new CagA types, which could not be typed by the existing systems and therefore, we have proposed a new typing system. We hypothesize that a cagA gene encoding higher number EPIYA motifs may perhaps have arisen from cagA genes that encode lesser EPIYA motifs by acquisition of DNA segments through recombination events.

VacA and cagA genotypes status and antimicrobial resistance properties of Helicobacter pylori strains isolated from meat products in Isfahan province, Iran.

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Gilani, A; Razavilar, V; Rokni, N; Rahimi, E

2017-01-01

Although Helicobacter pylori has a significant impact on the occurrence of severe clinical syndromes, its exact ways of transmission and origin have not been identified. According to the results of some previously published articles, foods with animal origins play a substantial role in the transmission of H. pylori to humans. The present investigation was carried out to study the vacuolating cytotoxin A ( vacA ) and cytotoxin associated gene A ( cagA ) genotypes status and antibiotic resistance properties of H. pylori strains recovered from minced-meat and hamburger samples. A total of 150 meat product samples were collected from supermarkets. All samples were cultured and the susceptive colonies were then subjected to nested-PCR, PCR-based genotyping and disk diffusion methods. 11 out of 150 samples (7.33%) were positive for H. pylori . All the isolates were further identified using the nested-PCR assay. Prevalence of H. pylori in hamburger and minced-meat samples was 1.42% and 12.5%, respectively. S1a , m1a and cagA were the most commonly detected genotypes. The most commonly detected combined genotypes in the H. pylori strains of minced-meat were s1am1a (10%), s1am1b (10%) and s2m1a (10%). Helicobacter pylori strains of meat products harbored the highest levels of resistance against ampicillin (90.90%), erythromycin (72.72%), amoxicillin (72.72%), trimethoprim (63.63%), tetracycline (63.63%), and clarithromycin (63.63%). Hamburger and minced-meat samples may be the sources of virulent and resistant strains of H. pylori . Meat products are possible sources of resistant and virulent strains of H. pylori similar to those vacA and cagA genotypes. Using healthy raw materials and observation of personal hygiene can reduce the risk of H. pylori in meat products.

Comparative genomics of Helicobacter pylori strains of China associated with different clinical outcome.

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Yuanhai You

Full Text Available In this study, a whole-genome CombiMatrix Custom oligonucleotide tiling microarray with 90,000 probes covering six sequenced Helicobacter pylori (H. pylori genomes was designed. This microarray was used to compare the genomic profiles of eight unsequenced strains isolated from patients with different gastroduodenal diseases in Heilongjiang province of China. Since significant genomic variation was found among these strains, an additional 76 H. pylori strains associated with different clinical outcomes were isolated from various provinces of China. These strains were tested by polymerase chain reaction to demonstrate this distinction. We identified several highly variable regions in strains associated with gastritis, gastric ulceration, and gastric cancer. These regions are associated with genes involved in the bacterial type I, type II, and type III R-M systems. They were also associated with the virB gene, which lies on the well-studied cag pathogenic island. While previous studies have reported on the diverse genetic characterization of this pathogenic island, in this study, we find that it is conserved in all strains tested by microarray. Moreover, a number of genes involved in the type IV secretion system, which is related to horizontal DNA transfer between H. pylori strains, were identified in the comparative analysis of the strain-specific genes. These findings may provide insight into new biomarkers for the prediction of gastric diseases.

Analysis of T4SS-induced signaling by H. pylori using quantitative phosphoproteomics

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Frithjof eGlowinski

2014-07-01

Full Text Available Helicobacter pylori is a Gram-negative bacterial pathogen colonizing the human stomach. Infection with H. pylori causes chronic inflammation of the gastric mucosa and may lead to peptic ulceration and/or gastric cancer. A major virulence determinant of H. pylori is the type IV secretion system (T4SS, which is used to inject the virulence factor CagA into the host cell, triggering a wide range of cellular signaling events. Here, we used a phosphoproteomic approach to investigate tyrosine signaling in response to host-pathogen interaction, using stable isotope labeling in cell culture (SILAC of AGS cells to obtain a differential picture between multiple infection conditions. Cells were infected with wild type H. pylori P12, a P12ΔCagA deletion mutant, and a P12ΔT4SS deletion mutant to compare signaling changes over time and in the absence of CagA or the T4SS. Tryptic peptides were enriched for tyrosine (Tyr phosphopeptides and analysed by nano-LC-Orbitrap MS. In total, 58 different phosphosites were found to be regulated following infection. The majority of phosphosites identified were kinases of the MAPK familiy. CagA and the T4SS were found to be key regulators of Tyr phosphosites. Our findings indicate that CagA primarily induces activation of ERK1 and integrin linked factors, whereas the T4SS primarily modulates JNK and p38 activation.

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

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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

Detection of Helicobacter pylori CagA and VacA genotypes from ...

African Journals Online (AJOL)

Background: Helicobacter pylori(H. Pylori) is one of the most common pathogens affecting human kind, infecting more than 50% of the world's population. Invasive and non- invasive methods have been used to diagnose H. pylori infection. The polymerase chain reaction (PCR) has been broadly and successfully used to ...

Helicobacter pylori cagA and vacA genotypes in Cuban and Venezuelan populations

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Diana Ortiz-Princz

2010-05-01

Full Text Available The aim of this study was to determine the presence of Helicobacter pylori cytotoxin-associated gene (cagA/vacuolating cytotoxin gene (vacA among patients with chronic gastritis in Cuba and Venezuela. Gastric antrum biopsies were taken for culture, DNA extraction and PCR analysis. Amplification of vacA and cagA segments was performed using two regions of cagA: 349 bp were amplified with the F1/B1 primers and the remaining 335 bp were amplified with the B7629/B7628 primers. The VA1-F/VA1-R set of primers was used to amplify the 259-bp (s1 or 286-bp (s2 product and the VAG-R/VAG-F set of primers was used to amplify the 567-bp (m1 or 642-bp (m2 regions of vacA. cagA was detected in 87% of the antral samples from Cuban patients and 80.3% of those from Venezuelan patients. All possible combinations of vacA regions were found, with the exception of s2/m1. The predominant combination found in both countries was s1/m1. The percentage of cagA+ strains was increased by the use of a second set of primers and a greater number of strains was amplified with the B7629/B7628 primers in the Cuban patients (p = 0.0001. There was no significant difference between the presence of the allelic variants of vacA and cagA in both populations. The predominant genotype was cagA+/s1m1 in both countries. The results support the necessary investigation of isolates circulating among the human population in each region.

Differential Mechanisms for SHP2 Binding and Activation Are Exploited by Geographically Distinct Helicobacter pylori CagA Oncoproteins

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Takeru Hayashi

2017-09-01

Full Text Available Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the East Asian CagA-specific EPIYA-D segment binds to the N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders of magnitude greater than Western CagA-specific EPIYA-C. This high-affinity binding is achieved via cryptic interaction between Phe at the +5 position from phosphotyrosine in EPIYA-D and a hollow on the N-SH2 phosphopeptide-binding floor. Also, duplication of EPIYA-C in Western CagA, which increases gastric cancer risk, enables divalent high-affinity binding with SHP2 via N-SH2 and C-SH2. These strong CagA bindings enforce enzymatic activation of SHP2, which endows cells with neoplastic traits. Mechanistically, N-SH2 in SHP2 is in an equilibrium between stimulatory “relaxed” and inhibitory “squeezed” states, which is fixed upon high-affinity CagA binding to the “relaxed” state that stimulates SHP2. Accordingly, East Asian CagA and Western CagA exploit distinct mechanisms for SHP2 deregulation.

Comparative genomics of a Helicobacter pylori isolate from a Chinese Yunnan Naxi ethnic aborigine suggests high genetic divergence and phage insertion.

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Yuanhai You

Full Text Available 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.

Relationship Between Helicobacter Pylori Infection and Chronic Obstructive Pulmonary Disease

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Mohammad-Ali Seif-Rabiei

2011-11-01

Full Text Available There is some evidence indicating the role of Helicobacter pylori infection in pathogenesis of extragastrointestinal diseases including skin, vascular, and autoimmune disorders, as well as some respiratory diseases. The aim of this study was to investigate the association between H. pylori and chronic obstructive pulmonary disease (COPD. In a case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history, and spirometric findings for each patient. Of 90 patients with COPD 66 (51% had mild, 31 (34.4% moderate, and 13 (14.4% sever disease. There was no significant association between H. pylori IgG seropositivity and COPD. Serum levels of anti-CagA IgG were significantly higher in patients with COPD than in the control subjects (P < 0.001. No association was observed between H. pylori infection and severity of COPD. The results suggest that there is an association between CagA-positive H. pylori infections and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms that might underlie these associations.

Helicobacter pylori and gastroduodenal pathology: New threats of the old friend

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Sechi Leonardo A

2005-01-01

Full Text Available Abstract The human gastric pathogen Helicobacter pylori causes chronic gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT lymphoma. It infects over 50% of the worlds' population, however, only a small subset of infected people experience H. pylori-associated illnesses. Associations with disease-specific factors remain enigmatic years after the genome sequences were deciphered. Infection with strains of Helicobacter pylori that carry the cytotoxin-associated antigen A (cagA gene is associated with gastric carcinoma. Recent studies revealed mechanisms through which the cagA protein triggers oncopathogenic activities. Other candidate genes such as some members of the so-called plasticity region cluster are also implicated to be associated with carcinoma of stomach. Study of the evolution of polymorphisms and sequence variation in H. pylori populations on a global basis has provided a window into the history of human population migration and co-evolution of this pathogen with its host. Possible symbiotic relationships were debated since the discovery of this pathogen. The debate has been further intensified as some studies have posed the possibility that H. pylori infection may be beneficial in some humans. This assumption is based on increased incidence of gastro-oesophageal reflux disease (GERD, Barrett's oesophagus and adenocarcinoma of the oesophagus following H. pylori eradication in some countries. The contribution of comparative genomics to our understanding of the genome organisation and diversity of H. pylori and its pathophysiological importance to human healthcare is exemplified in this review.

VacA, cagA, iceA and oipA genotypes status and antimicrobial resistance properties of Helicobacter pylori isolated from various types of ready to eat foods.

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Hemmatinezhad, Behsan; Momtaz, Hassan; Rahimi, Ebrahim

2016-01-20

Despite the high clinical standing of Helicobacter pylori, its exact routes of transmission and origin have not been determined. Based on the contentious hypothesis, foods play an important roles in the transmission of H. pylori to humans. The present study was carried out to investigate the vacA, cagA, oipA and iceA genotypes status of H. pylori isolated from the various types of ready to eat foods. A total of 550 ready to eat food samples were cultured and tested. H. pylori-positive strains were analyzed for the presence of various genotypes and antimicrobial resistance pattern. Seventy four out of 550 (13.45 %) samples were positive for H. pylori. Olvie salad (36 %), restaurant salad (30 %), fruit salad (28 %) and soup (22 %) were the most commonly contaminated. H. pylori strains harbored the highest levels of resistance against amoxicillin (94.59 %), ampicillin (93.24 %), metronidazole (89.18 %) and tetracycline (72.97 %). The most commonly detected genotypes were vacA s1a (78.37 %), vacA m2 (75.67 %), vacA m1a (51.35 %) and cagA (41.89 %). The prevalence of iceA1, iceA2 and oipA genotypes were 13.51, 4.05 and 18.91 %, respectively. S1am2 (70.27 %), s1am1a (39.18 %) and m1am2 (31.08 %) were the most commonly detected combined genotypes. Of 40 different genotypic combinations, s1a/cagA+/iceA1/oipA- (12.16 %), s1a/cagA+/iceA1/oipA+ (10.81 %) and s1a/cagA-/iceA1/oipA+ (10.81 %) were the most prevalent. The present investigation showed that some types of ready to eat food samples maybe the sources of resistant and virulent strains of H. pylori. Warily use of antibiotics with respect to the results of disk diffusion method and careful health monitoring on food and staffs of food producing companies maybe reduce the risk of H. pylori in foods.

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

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Ivana Hitkova

Full Text Available 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.

The significance of virulence factors in Helicobacter pylori.

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Shiota, Seiji; Suzuki, Rumiko; Yamaoka, Yoshio

2013-07-01

Helicobacter pylori (H. pylori) infection is linked to various gastroduodenal diseases; however, only a small fraction of these patients develop associated 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 those in other countries. The incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographical differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors in addition to host and environmental factors. Virulence factors of H. pylori, such as CagA, VacA, DupA, IceA, OipA and BabA, have been demonstrated to be the predictors of severe clinical outcomes. Interestingly, a meta-analysis showed that CagA seropositivity was associated with gastric cancer compared with gastritis, even in East Asian countries where almost the strains possess cagA. Another meta-analysis also confirmed the significance of vacA, dupA and iceA. However, it is possible that additional important pathogenic genes may exist because H. pylori consists of approximately 1600 genes. Despite the advances in our understanding of the development of H. pylori infection-related diseases, further work is required to clarify the roles of H. pylori virulence factors. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer.

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Wang, Ming-yi; Chen, Cheng; Gao, Xiao-zhong; Li, Jie; Yue, Jing; Ling, Feng; Wang, Xiao-chun; Shao, Shi-he

2013-01-01

Helicobacter pylori (H. pylori) is a major human pathogen that is responsible for various gastroduodenal diseases. We investigated the prevalence of H. pylori virulence markers in a region at high risk of gastric cancer. One hundred and sixteen H. pylori strains were isolated from patients with gastroduodenal diseases. cagA, the cagA 3' variable region, cagPAI genes, vacA, and dupA genotypes were determined by PCR, and some amplicons of the cagA 3' variable region, cagPAI genes and dupA were sequenced. cagA was detected in all strains. The cagA 3' variable region of 85 strains (73.3%) was amplified, and the sequences of 24 strains were obtained including 22 strains possessing the East Asian-type. The partial cagPAI presented at a higher frequency in chronic gastritis (44.4%) than that of the severe clinical outcomes (9.7%, p dupA and sequencing of dupA revealed an ORF of 2449-bp. The prevalence of dupA was significantly higher in strains from patients with the severe clinical outcomes (40.3%) than that from chronic gastritis (20.4%, p = 0.02). The high rate of East Asian-type cagA, intact cagPAI, virulent vacA genotypes, and the intact long-type dupA may underlie the high risk of gastric cancer in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis

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Cheng-Yen Kao

2016-02-01

Full Text Available Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1 Survival in the acidic stomach; (2 movement toward epithelium cells by flagella-mediated motility; (3 attachment to host cells by adhesins/receptors interaction; (4 causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.

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).

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Ferreira Júnior, M; 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; Gomes, A D; Araújo, I D; Queiroz, D M M; Caliari, M V

2015-04-27

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.

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

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M. Ferreira Júnior

2015-04-01

Full Text Available 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.

Helicobacter pylori cagL amino acid polymorphism D58E59 pave the way toward peptic ulcer disease while N58E59 is associated with gastric cancer in north of Iran.

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Cherati, Mina Rezaee; Shokri-Shirvani, Javad; Karkhah, Ahmad; Rajabnia, Ramzan; Nouri, Hamid Reza

2017-06-01

The cagL protein of Helicobacter pylori involving in pathogenesis of gastroduodenal disorders. Therefore, the current study was conducted to determine the cagL amino acid polymorphisms in patients with gastric diseases. One hundred gastric biopsies were collected from gastritis, peptic ulcer (PUD) and gastric cancer (GC) patients and were screened for cagL using polymerase chain reaction (PCR). Also, sequence variations of the cagL were assessed via sequence translation. The cagL geneopositivity was 71.6% in patients were infected with H. pylori. The cagL from PUD indicated a higher rate of D58 amino acid sequence polymorphism than those of the GC and gastritis (P peptic ulcer. However, amino acid N, M, Q and N at the same position alongside V134 increased the risk of gastric cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral vaccination with attenuated Salmonella choleraesuis C500 ...

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user

Marshall, 1983), and well known as the major gastro- duodenal ... The CagA is encoded in a pathogenicity island known as 'Cag PAI' and is .... HindIII to release the CagA fragment. The purified .... vaccine strain attenuated by chemical methods, which is .... pylori antigens is achieved using a non-toxic mutant of E. coli heat-.

A novel system of cytoskeletal elements in the human pathogen Helicobacter pylori.

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Barbara Waidner

2009-11-01

Full Text Available Pathogenicity of the human pathogen Helicobacter pylori relies upon its capacity to adapt to a hostile environment and to escape from the host response. Therefore, cell shape, motility, and pH homeostasis of these bacteria are specifically adapted to the gastric mucus. We have found that the helical shape of H. pylori depends on coiled coil rich proteins (Ccrp, which form extended filamentous structures in vitro and in vivo, and are differentially required for the maintenance of cell morphology. We have developed an in vivo localization system for this pathogen. Consistent with a cytoskeleton-like structure, Ccrp proteins localized in a regular punctuate and static pattern within H. pylori cells. Ccrp genes show a high degree of sequence variation, which could be the reason for the morphological diversity between H. pylori strains. In contrast to other bacteria, the actin-like MreB protein is dispensable for viability in H. pylori, and does not affect cell shape, but cell length and chromosome segregation. In addition, mreB mutant cells displayed significantly reduced urease activity, and thus compromise a major pathogenicity factor of H. pylori. Our findings reveal that Ccrp proteins, but not MreB, affect cell morphology, while both cytoskeletal components affect the development of pathogenicity factors and/or cell cycle progression.

The frequency of Helicobacter pylor infection and cagA expression in the Korean patients with gastric carcinoma

International Nuclear Information System (INIS)

Jung, Sook Hyang; Kim, Yoo Chul

1997-12-01

Helicobacter pylori infection had been approved as a group 1 carcinogen by the international agency for research on cancer. However the association between H.pylori infection and gastric carcinoma was not so definite in South Asia including Korea, and the role of cagA gene of H.pylori in gastric carcinogenesis was a controversial issue. The aims of this study were firstly to study in vivo expression frequency of 16S rRNA and cagA gene of H.pylori, secondly to study the association between H.pylori infection and gastric cancer, the association between cagA expression and gastric cancer in Korean patients. In vivo expression rate of 16S rRNA was 74 % of gastric carcinoma patients and cagA expression rate was 51 % of gastric carcinoma patients with H.pylori infection. Although 90 % of gastric carcinoma patients had H.pylori infection, the association between H.pylori infection and gastric carcinoma was not significant. And there was no significant association between cagA expression and gastric carcinoma. (author). 37 refs., 2 tabs., 1 fig

The frequency of Helicobacter pylor infection and cagA expression in the Korean patients with gastric carcinoma

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Jung, Sook Hyang; Kim, Yoo Chul [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1997-12-01

Helicobacter pylori infection had been approved as a group 1 carcinogen by the international agency for research on cancer. However the association between H.pylori infection and gastric carcinoma was not so definite in South Asia including Korea, and the role of cagA gene of H.pylori in gastric carcinogenesis was a controversial issue. The aims of this study were firstly to study in vivo expression frequency of 16S rRNA and cagA gene of H.pylori, secondly to study the association between H.pylori infection and gastric cancer, the association between cagA expression and gastric cancer in Korean patients. In vivo expression rate of 16S rRNA was 74 % of gastric carcinoma patients and cagA expression rate was 51 % of gastric carcinoma patients with H.pylori infection. Although 90 % of gastric carcinoma patients had H.pylori infection, the association between H.pylori infection and gastric carcinoma was not significant. And there was no significant association between cagA expression and gastric carcinoma. (author). 37 refs., 2 tabs., 1 fig.

Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

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Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

2014-12-01

Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

Epstein Barr virus and Helicobacter pylori co-infection are positively associated with severe gastritis in pediatric patients.

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María G Cárdenas-Mondragón

Full Text Available H. pylori infection is acquired during childhood and causes a chronic inflammatory response in the gastric mucosa, which is considered the main risk factor to acquire gastric cancer (GC later in life. More recently, infection by Epstein-Barr virus (EBV have also been associated with GC. The role of EBV in early inflammatory responses and its relationship with H. pylori infection remains poorly studied. Here, we assessed whether EBV infection in children correlated with the stage of gastritis and whether co-infection with H. pylori affected the severity of inflammation.333 pediatric patients with chronic abdominal pain were studied. From them, gastric biopsies were taken and inflammation graded according to the Sydney system; peripheral blood was drawn and antibodies against EBV (IgG and IgM anti-VCA and H. pylori (IgG anti-whole bacteria and anti-CagA were measured in sera. We found that children infected only by EBV presented mild mononuclear (MN and none polymorphonuclear (PMN cell infiltration, while those infected by H. pylori presented moderate MN and mild PMN. In contrast, patients co-infected with both pathogens were significantly associated with severe gastritis. Importantly, co-infection of H. pylori CagA+/EBV+ had a stronger association with severe MN (PR 3.0 and PMN (PR 7.2 cells than cases with single H. pylori CagA+ infection.Co-infection with EBV and H. pylori in pediatric patients is associated with severe gastritis. Even single infections with H. pylori CagA+ strains are associated with mild to moderate infiltration arguing for a cooperative effect of H. pylori and EBV in the gastric mucosa and revealing a critical role for EBV previously un-appreciated. This study points out the need to study both pathogens to understand the mechanism behind severe damage of the gastric mucosa, which could identified children with increased risk to present more serious lesions later in life.

Infección por Helicobacter pylori en la Ciudad de La Habana, Cuba.Prevalencia de las cepas cagA positivas

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Beatriz Gutiérrez

2005-12-01

Full Text Available Existe una gran falta de información acerca de la infección por Helicobacter pylori en los países de la región del Caribe. Nuestros objetivos en este estudio fueron determinar la prevalencia, la resistencia a los antibióticos y los factores de virulencia de la bacteria. La medida de la prevalencia de la infección por H. pylori se determinó en un grupo de pacientes a los que se les practicó una endoscopia en tres centros hospitalarios de La Ciudad de La Habana, lo que nos permitió evaluar la resistencia a la claritromicina y la presencia de cagA + en las cepas obtenidas. De las endoscopias realizadas se obtuvieron 117 biopsias gástricas, procedentes de tres centros hospitalarios de La Ciudad de La Habana, Cuba: Instituto de Oncología, Instituto de Gastroenterología y el Hospital Calixto García. Las biopsias fueron mantenidas a –70 ºC para posterior cultivo en tres medios diferentes (dos selectivos y uno no selectivo y su posterior incubación por 7 días a 37 ºC en una atmósfera de microaerofilia. La presencia de H. pylori fue identificada por la presencia de diferentes enzimas (oxidasa, catalasa, ureasa. Se realizó la extracción del DNA y la PCR, donde se utilizó el primer H2761676 y se amplificó con 397 fragmentos del gen cagA. La susceptibilidad a la claritromicina fue medida por el método de difusión en gel. Diagnóstico endoscópico: (1 cáncer gástrico; (19 úlcera duodenal; (8 úlcera gástrica; (89 dispepsias no ulcerosas, incluyendo (62 gastritis; (9 hernia hiatal; (2 reflujo biliar; (1 pólipo gástrico; (15 panendoscopias normales. Del total de 117 biopsias realizadas, 83 fueron positivas a la infección por H.pylori (70,9% . De las 35 cepas a las que se les realizó presencia de cagA+ resultaron positivas 31 (88,5%. Solo el 3% de las cepas fueron resistentes a la claritromicina. La prevalencia de la infección por H. pylori en la población sintomática de La Ciudad de La Habana es la misma que la reportada en

Structural biology studies of CagA from Helicobacter pylori and histone chaperone CIA/ASF1

International Nuclear Information System (INIS)

Senda, Toshiya

2015-01-01

Crystal structures of proteins and their complexes have become critical information for molecular-based life science. Biochemical and biological analysis based on tertiary structural information is a powerful tool to unveil complex molecular processes in the cell. Here, we present two examples of the structure-based life science study, structural biology studies of CagA, an effector protein from Helicobacter pylori, and histone chaperone CIA/ASF1, which is involved in transcription initiation. (author)

On the importance of developing a new generation of breath tests for Helicobacter pylori detection.

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Kushch, Ievgeniia; Korenev, Nikolai; Kamarchuk, Lyudmila; Pospelov, Alexander; Kravchenko, Andrey; Bajenov, Leonid; Kabulov, Mels; Amann, Anton; Kamarchuk, Gennadii

2015-12-15

State-of-the-art methods for non-invasive detection of the Helicobacter pylori (H. pylori) infection have been considered. A reported global tendency towards a non-decreasing prevalence of H. pylori worldwide could be co-influenced by the functional limitations of urea breath tests (UBTs), currently preferred for the non-invasive recognition of H. pylori in a clinical setting. Namely, the UBTs can demonstrate false-positive or false-negative results. Within this context, limitations of conventional clinically exploited H. pylori tests have been discussed to justify the existing need for the development of a new generation of breath tests for the detection of H. pylori and the differentiation of pathogenic and non-pathogenic strains of the bacterium. This paper presents the results of a pilot clinical study aimed at evaluating the development and diagnostic potential of a new method based on the detection of the non-urease products of H. pylori vital activity in exhaled gas. The characteristics of breath of adolescents with H. pylori-positive and H. pylori-negative functional dyspepsia, together with a consideration of the cytotoxin-associated gene A (CagA) status of H. pylori-positive subjects, have been determined for the first time using innovative point-contact nanosensor devices based on salts of the organic conductor tetracyanoquinodimethane (TCNQ). The clinical and diagnostic relevance of the response curves of the point-contact sensors was assessed. It was found that the recovery time of the point-contact sensors has a diagnostic value for differentiation of the H. pylori-associated peptic ulcer disease. The diagnostically significant elongation of the recovery time was even more pronounced in patients infected with CagA-positive H. pylori strains compared to the CagA-negative patients. Taking into account the operation of the point-contact sensors in the real-time mode, the obtained results are essential prerequisites for the development of a fast and

Variation in the number of EPIYA-C repeats in CagA protein from Colombian Helicobacter pylori strains and its ability to induce hummingbird phenotype in gastric epithelial cells Variación en el número de repeticiones EPIYA-C en la proteína CagA de aislamientos colombianos de Helicobacter pylori y su capacidad para inducir fenotipo colibrí en células epiteliales gástricas

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María Mercedes Bravo

2010-08-01

Full Text Available Introduction. Studies using Western Helicobacter pylori strains have shown that a risk factor for gastric cancer is the number of EPIYA-C motifs in the cytotoxin-associated A protein. CagA is delivered into epithelial cells, where it becomes tyrosine phosphorylated in their EPIYA repeats and induces cytoskeleton rearrangements.
Objectives. The objective of this study was to evaluate H. pylori cagA positive strains isolated from Colombian patients with gastroduodenal diseases for the number of EPIYA-C repeats in cagA and their ability to induce cytoskeleton rearrangements in epithelial cells.
Materials and methods. We analyzed the 3' EPIYA repeats region of cagA by PCR in 93 H. pylori cagA positive strains from 49 patients with gastritis, 17 with gastric cancer, and 24 with duodenal ulcer. AGS cells exposed to the various H. pylori isolates were evaluated for rearrangements in their cytoskeleton.
Results. Strains with one EPIYA-C were the most frequent in gastritis and duodenal ulcer patients. Strains with three EPIYA-C were mainly found in gastric cancer. We found a significantly higher risk of gastric cancer for individuals infected with strains harboring three EPIYA-C motifs (OR=12.4, CI95%: 2.32-66.3. Strains from gastric cancer showed significantly higher percentages of induction of cytoskeleton rearrangements in comparison with those from gastritis (p Mann-Whitney<0.005.
Conclusions. H. pylori strains with three EPIYA-C repeats can confer an increased risk of cancer to infected individuals.Introducción. En los aislamientos de Helicobacter pylori del hemisferio occidental, se ha observado que el número de repeticiones EPIYA-C en la proteína CagA es un factor de riesgo para cáncer gástrico. La proteína CagA es introducida en la célula epitelial y, posteriormente, es fosforilada en las tirosinas presentes en los motivos EPIYA e induce rearreglos en el citoesqueleto.
Objetivos. Nuestro propósito fue evaluar el n

Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

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Hsueh-Fen Juan

2012-08-01

Full Text Available Helicobacter pylori (H. pylori, the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+, single mutant (ΔvacA or ΔcagA or double mutant (ΔvacA/ΔcagA strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca²⁺ influx. Ca²⁺-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.

STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer

International Nuclear Information System (INIS)

Rocha, Gifone A; Rocha, Andreia MC; Gomes, Adriana D; Faria, César LL Jr; Melo, Fabrício F; Batista, Sérgio A; Fernandes, Viviane C; Almeida, Nathálie BF; Teixeira, Kádima N; Brito, Kátia S; Queiroz, Dulciene Maria Magalhães

2015-01-01

Because to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer. We included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model. The rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p < 0.001; OR = 3.01; 95 % CI = 2.29-3.98). When stimulated with LPS (lipopolysaccharide) or Pam3Cys, peripheral mononuclear cells of healthy carriers of the rs744166 GG and AG genotypes expressed higher levels of STAT3 mRNA than those carrying AA genotype (p = 0.04 for both). The nuclear expression of phosphorylated p-STAT3 protein was significantly higher in the antral gastric tissue of carriers of rs744166 GG genotype than in carriers of AG and AA genotypes. Our study provides evidence that STAT3 rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer. The odds ratio of having gastric cancer was greater when bacterium and host high risk genotypes were combined

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

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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 ...

Pathogenesis of Helicobacter pylori-Related Gastroduodenal Diseases from Molecular Epidemiological Studies.

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Yamaoka, Yoshio

2012-01-01

Helicobacter pylori is a major human pathogen that infects the stomach and produces inflammation that is responsible for various gastroduodenal diseases. Despite the high prevalence of H. pylori infections in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. The incidence of gastric cancer also tends to decrease from north to south in East Asia. Data from molecular epidemiological studies show that this variation in different geographic areas could be explained in part by different types of H. pylori virulence factors, especially CagA, VacA, and OipA. H. pylori infection is thought to be involved in both gastric cancer and duodenal ulcer, which are at opposite ends of the disease spectrum. This discrepancy can also be explained in part by another H. pylori factor, DupA, as well as by CagA typing (East Asian type versus Western type). H. pylori has a genome of approximately 1,600 genes; therefore, there might be other novel virulence factors. Because genome wide analyses using whole-genome sequencing technology give a broad view of the genome of H. pylori, we hope that next-generation sequencers will enable us to efficiently investigate novel virulence factors.

Pathogenesis of Helicobacter pylori-Related Gastroduodenal Diseases from Molecular Epidemiological Studies

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Yoshio Yamaoka

2012-01-01

Full Text Available Helicobacter pylori is a major human pathogen that infects the stomach and produces inflammation that is responsible for various gastroduodenal diseases. Despite the high prevalence of H. pylori infections in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. The incidence of gastric cancer also tends to decrease from north to south in East Asia. Data from molecular epidemiological studies show that this variation in different geographic areas could be explained in part by different types of H. pylori virulence factors, especially CagA, VacA, and OipA. H. pylori infection is thought to be involved in both gastric cancer and duodenal ulcer, which are at opposite ends of the disease spectrum. This discrepancy can also be explained in part by another H. pylori factor, DupA, as well as by CagA typing (East Asian type versus Western type. H. pylori has a genome of approximately 1,600 genes; therefore, there might be other novel virulence factors. Because genome wide analyses using whole-genome sequencing technology give a broad view of the genome of H. pylori, we hope that next-generation sequencers will enable us to efficiently investigate novel virulence factors.

Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

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Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

2017-12-01

Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 + T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

Host pathogen interactions in Helicobacter pylori related gastric cancer

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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

Clonación y expresión de un fragmento recombinante del gen cagA de Helicobacter pylori y su evaluación preliminar en el serodiagnóstico

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Lidice González

2013-12-01

100 % y 92,7 %, respectivamente. Conclusiones. El fragmento de la proteína CagA del estudio puede constituir una herramienta útil para el diagnóstico serológico de la infección por cepas de H. pylori positivas para CagA. doi: http://dx.doi.org/10.7705/biomedica.v33i4.1678

Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis.

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Shiota, Seiji; Watada, Masahide; Matsunari, Osamu; Iwatani, Shun; Suzuki, Rumiko; Yamaoka, Yoshio

2012-01-01

Although the iceA (induced by contact with epithelium) allelic types of Helicobacter pylori have been reported to be associated with peptic ulcer, the importance of iceA on clinical outcomes based on subsequent studies is controversial. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with iceA. A literature search was performed using the PubMed and EMBASE databases for articles published through April 2011. Published case-control studies examining the relationship between iceA and clinical outcomes (gastritis, peptic ulcer, including gastric ulcer and duodenal ulcer, and gastric cancer) were included. Fifty studies with a total of 5,357 patients were identified in the search. Infection with iceA1-positive H. pylori increased the overall risk for peptic ulcer by 1.26-fold (95% confidence interval [CI], 1.09-1.45). However, the test for heterogeneity was significant among these studies. Sensitivity analysis showed that the presence of iceA1 was significantly associated with peptic ulcer (odds ratio [OR] = 1.25, 95% CI = 1.08-1.44). The presence of iceA2 was inversely associated with peptic ulcer (OR = 0.76, 95% CI = 0.65-0.89). The presence of iceA was not associated with gastric cancer. Most studies examined the cagA status; however, only 15 studies examined the correlation and only 2 showed a positive correlation between the presence of cagA and iceA1. Our meta-analysis confirmed the importance of the presence of iceA for peptic ulcer, although the significance was marginal.

Comparative Analysis of two Helicobacter pylori Strains using Genomics and Mass Spectrometry-Based Proteomics

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Roger Karlsson

2016-11-01

Full Text Available Helicobacter pylori, a gastroenteric pathogen believed to have co-evolved with humans over 100,000 years, shows significant genetic variability. This motivates the study of different H. pylori strains and the diseases they cause in order to identify determinants for disease evolution. In this study, we used proteomics tools to compare two H. pylori strains. Nic25_A was isolated in Nicaragua from a patient with intestinal metaplasia, and P12 was isolated in Europe from a patient with duodenal ulcers. Differences in the abundance of surface proteins between the two strains were determined with two mass spectrometry-based methods, label-free quantification (MaxQuant or the use of tandem mass tags (TMT. Each approach used a lipid-based protein immobilization (LPI™ technique to enrich peptides of surface proteins. Using the MaxQuant software, we found 52 proteins that differed significantly in abundance between the two strains (up- or downregulated by a factor of 1.5; with TMT, we found 18 proteins that differed in abundance between the strains. Strain P12 had a higher abundance of proteins encoded by the cag pathogenicity island, while levels of the acid response regulator ArsR and its regulatory targets (KatA, AmiE, and proteins involved in urease production were higher in strain Nic25_A. Our results show that differences in protein abundance between H. pylori strains can be detected with proteomic approaches; this could have important implications for the study of disease progression.

Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells

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Max Koeppel

2015-06-01

Full Text Available Infection with the human pathogen Helicobacter pylori (H. pylori is a major risk factor for gastric cancer. Since the bacterium exerts multiple genotoxic effects, we examined the circumstances of DNA damage accumulation and identified regions within the host genome with high susceptibility to H. pylori-induced damage. Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes. We thus demonstrate an impact of a bacterial infection directed toward specific host genomic regions and describe underlying characteristics that make such regions more likely to acquire heritable changes during infection, which could contribute to cellular transformation.

Medicinal plant activity on Helicobacter pylori related diseases

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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 ...

Peptic Ulcer Disease and Helicobacter pylori Infection in Different Siberian Ethnicities.

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Tsukanov, Vladislav V; Kasparov, Edward V; Tonkikh, Julia L; Shtygasheva, Olga V; Butorin, Nikolay N; Amelchugova, Olga S; Vasyutin, Alexander V; Bronnikova, Elena P; Fassan, Matteo; Rugge, Massimo

2017-02-01

The high prevalence of Helicobacter pylori (H. pylori) infection in eastern Siberia is consistently established. In the same geographic area, however, fragmentary information is available on the epidemiology of the peptic ulcer disease (PUD). To assess the prevalence of H. pylori infection (including CagA status) and PUD in different eastern Siberian ethnicities. An endoscopy population of 3149 eastern Siberian dyspeptic patients was considered [1727 Europoids and 1422 Mongoloids (Evenks = 792; Khakases = 630)]. H. pylori status was assessed by urease test and/or serum anti-H. pylori IgG and/or histology. CagA status was serologically assessed (anti-CagA antibodies). All the Siberian ethnicities featured high rates of H. pylori infection (Europoids = 87.1%, Evenks = 88.6%, Khakases = 85.4%). Among the 1504 H. pylori-positive Europoids, the prevalence of CagA-positive status (68.7%) was significantly higher than that featured by the 1240 H. pylori-positive Mongoloid ethnicities (46.9%; p Peptic ulcer disease significantly prevailed among Europoids (prevalence among Europoid Evenks and Khakases: 8.9% and 8.3%, respectively; prevalence among Mongoloid Evenks and Khakases = 1.0% and 4.4%, respectively). eastern Siberian populations feature consistent high rates of H. pylori infection, but different prevalence of peptic ulcer disease. In particular, Europoids featured a prevalence of both CagA-positive status and peptic ulcer disease significantly higher than that of the Mongoloid ethnicities. These results suggest that both environmental factors (coexisting with the H. pylori infection) and host-related variables modulate the clinicopathological expression of the H. pylori -associated gastric diseases. © 2016 John Wiley & Sons Ltd.

Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention.

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Cosmeri Rizzato

Full Text Available Helicobacter pylori (HP is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes pathogenicity island (cagPAI, a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS. This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous showed statistically significant differences (P<0.05, and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value = 2.07×10⁻⁶, and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations.

The intact dupA cluster is a more reliable Helicobacter pylori virulence marker than dupA alone.

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

2012-01-01

The duodenal ulcer promoting (dupA) gene, located in the plasticity region of Helicobacter pylori, is associated with duodenal ulcer development. dupA was predicted to form a type IV secretory system (T4SS) with vir genes around dupA (dupA cluster). We investigated the prevalence of dupA and dupA clusters and clarified associations between the dupA cluster status and clinical outcomes in the U.S. population. In all, 245 H. pylori strains were examined using PCR to evaluate the status of dupA and the adjacent vir genes predicted to form T4SS, in addition to the status of cag pathogenicity island (PAI). The associations between dupA cluster status and interleukin-8 (IL-8) and IL-12 production were also examined. The presence of dupA and all adjacent vir genes were defined as a complete dupA cluster. Many variations related to the status of dupA and dupA cluster genes were identified. Concurrent H. pylori infection and the presence of a complete dupA cluster increases duodenal ulcer risk compared to H. pylori infection with incomplete dupA cluster or without the dupA gene independent on the cag PAI status (adjusted odds ratio, 2.13; 95% confidence interval, 1.13 to 4.03). Gastric mucosal IL-8 levels were also significantly higher in the complete dupA cluster group than in other groups (P=0.01). In conclusion, although the causal relationship between the dupA cluster and duodenal ulcer development is not proved, the presence of a complete dupA cluster but not dupA alone, is associated with duodenal ulcer development.

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

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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.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer.

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Yoshida, Takeichi; Kato, Jun; Inoue, Izumi; Yoshimura, Noriko; Deguchi, Hisanobu; Mukoubayashi, Chizu; Oka, Masashi; Watanabe, Mika; Enomoto, Shotaro; Niwa, Toru; Maekita, Takao; Iguchi, Mikitaka; Tamai, Hideyuki; Utsunomiya, Hirotoshi; Yamamichi, Nobutake; Fujishiro, Mitsuhiro; Iwane, Masataka; Takeshita, Tatsuya; Ushijima, Toshikazu; Ichinose, Masao

2014-03-15

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects. © 2013 UICC.

Molecular interactions between MUC1 epithelial mucin, β-catenin, and CagA proteins

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Wei eGuang

2012-05-01

Full Text Available Interleukin (IL-8-driven neutrophil infiltration of the gastric mucosa is pathognomonic of persistent Helicobacter pylori infection. Our prior study showed that ectopic over-expression of MUC1 in human AGS gastric epithelial cells reduced H. pylori-stimulated IL-8 production compared with cells expressing MUC1 endogenously. Conversely, Muc1 knockout (Muc1-/- mice displayed an increased level of transcripts encoding the keratinocyte chemoattractant (KC, the murine equivalent of human IL-8, in gastric mucosa compared with Muc1(+/+ mice during experimental H. pylori infection. The current study tested the hypothesis that a decreased IL-8 level observed following MUC1 over-expression is mediated through the ability of MUC1 to associate with β-catenin, thereby inhibiting H. pylori-induced β-catenin nuclear translocation. Increased neutrophil infiltration of the gastric mucosa of H. pylori-infected Muc1(-/- mice was observed compared with Muc1(+/+ wild type littermates, thus defining the functional consequences of increased KC expression in the Muc1-null animals. Protein co-immunoprecipitation (coIP studies using lysates of untreated or H. pylori-treated AGS cells demonstrated that (a MUC1 formed a coIP complex with β-catenin and CagA, (b MUC1 over-expression reduced CagA/β-catenin coIP, and (c in the absence of MUC1 over-expression, H. pylori infection increased the nuclear level of β-catenin, (d whereas MUC1 over-expression decreased bacteria-driven β-catenin nuclear localization. These results suggest that manipulation of MUC1 expression in gastric epithelia may be an effective therapeutic strategy to inhibit H. pylori-dependent IL-8 production, neutrophil infiltration, and stomach inflammation.

Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

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Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

2017-01-01

Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

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

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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

Helicobacter pylori seropositivity and risk of lung cancer.

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Jill Koshiol

Full Text Available Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA antigens, we calculated odds ratios (ORs and 95% confidence intervals (95% CIs for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6 or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7. Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.

Positive selection on a bacterial oncoprotein associated with gastric cancer

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Delgado-Rosado Gisela

2011-11-01

Full Text Available Background Helicobacter pylori is a vertically inherited gut commensal that is carcinogenic if it possesses the cag pathogenicity island (cag PaI; infection with H.pylori is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO. The cag PaI locus encodes the cagA gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the cag PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking. Results Here, we reveal that the cagA gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the cagA gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations. Conclusion Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of H.pylori between hosts

Frequency of virulence factors in Helicobacter pylori-infected patients with gastritis.

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Salimzadeh, Loghman; Bagheri, Nader; Zamanzad, Behnam; Azadegan-Dehkordi, Fatemeh; Rahimian, Ghorbanali; Hashemzadeh-Chaleshtori, Morteza; Rafieian-Kopaei, Mahmoud; Sanei, Mohammad Hossein; Shirzad, Hedayatollah

2015-03-01

The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The vacuolating cytotoxin (vacA), cagA gene, oipA and babA2 gene are important virulence factor involving gastric diseases. The objective of this study was to assess the relationship between virulence factors of H. pylori and histopathological findings. Gastroduodenoscopy was performed in 436 dyspeptic patients. Antrum biopsy was obtained for detection of H. pylori, virulence factors and for histopathological assessment. The polymerase chain reaction was used to detect virulence factors of H. pylori using specific primers. vacA genotypes in patients infected with H. pylori were associated with cagA, iceA1 and iceA2. In the patients with H. pylori infection there was a significant relationship between cagA positivity and neutrophil activity (P = 0.004) and chronic inflammation (P = 0.013) and with H. pylori density (P = 0.034). Neutrophil infiltration was found to be more severe in the s1 group than in the s2 group (P = 0.042). Also was a significant relationship between oipA positivity and neutrophil activity (P = 0.004) and with H. pylori density (P = 0.018). No significant relationships were observed between other vacA genotypes and histopathological parameters. H. pylori strains showing cagA, vacA s1 and oipA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic affinities of Helicobacter pylori isolates from ethnic Arabs in Kuwait

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Albert M John

2010-07-01

Full Text Available Abstract Helicobacter pylori is one of the most genetically diverse of bacterial species, and since the 5'-end of cagA gene and the middle allele of vacA gene of H. pylori from different populations exhibit considerable polymorphisms, these sequence diversities were used to gain insights into the genetic affinities of this gastric pathogen from different populations. Because the genetic affinity of Arab strains from the Arabian Gulf is not known, we carried out genetic analysis based on sequence diversities of the cagA and the vacA genes of H. pylori from 9 ethnic Arabs in Kuwait. The analysis showed that the Kuwaiti isolates are closely related to the Indo-European group of strains, although some strains have a tendency to form a separate cluster close to the Indo- European group, but clearly distinct from East Asian strains. However, these results need to be confirmed by analyses of neutral markers (house-keeping genes in a multi-locus sequence typing [MLST] platform. The profiling of virulence-associated genes may have resulted from ecologically distinct populations due to human migration and geographical separation over long periods of time.

Mechanisms of disease: Helicobacter pylori virulence factors.

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Yamaoka, Yoshio

2010-11-01

Helicobacter pylori plays an essential role in the development of various gastroduodenal diseases; however, only a small proportion of people infected with H. pylori develop these diseases. Some populations that have a high prevalence of H. pylori infection also have a high incidence of gastric cancer (for example, in East Asia), whereas others do not (for example, in Africa and South Asia). Even within East Asia, the incidence of gastric cancer varies (decreasing in the south). H. pylori is a highly heterogeneous bacterium and its virulence varies geographically. Geographic differences in the incidence of gastric cancer can be explained, at least in part, by the presence of different types of H. pylori virulence factor, especially CagA, VacA and OipA. However, it is still unclear why the pathogenicity of H. pylori increased as it migrated from Africa to East Asia during the course of evolution. H. pylori infection is also thought to be involved in the development of duodenal ulcer, which is at the opposite end of the disease spectrum to gastric cancer. This discrepancy can be explained in part by the presence of H. pylori virulence factor DupA. Despite advances in our understanding of the development of H. pylori-related diseases, further work is required to clarify the roles of H. pylori virulence factors.

Human Gastric Mucosal Hydrophobicity Does dot Decrease with Helicobacter Pylori Infection or Chronological Age

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Mohammed S Al-Marhoon

2005-01-01

Full Text Available BACKGROUND AND AIMS: Infection with cytotoxin-associated gene A (cagA Helicobacter pylori is associated with severe gastric diseases. Previous studies in humans have reported a decreased gastric hydrophobicity with H pylori infection. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus hydrophobicity.

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

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

2015-07-01

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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genotyping of Helicobacter pylori Strains Isolated from Patients with Gastric Ulcer and Non Ulcer Disease using RFLP-PCR of ureAB, vacA , cagA Genes

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Sh. Farshad

2008-10-01

Full Text Available Introduction & Objective: Different studies show that the reasons for clinically diverse outcomes of infections caused by H. pylori may include host and environmental factors as well as differences in the prevalence or expression of bacterial virulence factors. The aim of this study was to study the distribution of different genotypes of major virulence factors cagA, vacA and ureAB among H. pylori strains isolated from patients with gastric ulcer (ulcerative disease and patients with gastritis (non ulcerative disease.Materials & Methods: In this cross sectional study 65 H. pylori strains, 30 from patients with gastric ulcer and 35 from patients with non ulcerative gastritis disease were investigated by RFLP-PCR.Results: The prevalence of vacA-positive strains in ulcerative patients was significantly more than that in non ulcerative patients (P0.05.Conclusion: It seems that in the patients under our study the presence of cagA gene may not necessarily be a risk factor for ulcer disease, while a homologous genotype of vacA appears to be associated with an increase risk of ulcer development. Lastly, despite the existence of a high degree of genomic variability within ureAB, conserved DNA banding profiles are distributed in our areas.

Helicobacter pylori - a seasoned pathogen by any other name

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Ahmed Niyaz

2009-12-01

Full Text Available Abstract Helicobacter pylori is a well known inhabitant of human stomach which is linked to peptic ulcer disease and gastric adenocarcinoma. It was recently shown in several studies that H. pylori can be harnessed as a surrogate marker of human migration and that its population structure and stratification patterns exactly juxtapose to those of Homo sapiens. This is enough a testimony to convey that H. pylori may have coevolved with their host. Several protective effects of H. pylori colonization have been considered as evidence of a presumed symbiotic relationship. Contrary to this assumption is the presence of a strong virulence apparatus within H. pylori; why a co-evolved parasite would try inflicting its host with serious infection and even causing cancer? The answer is perhaps embedded in the evolutionary history of both the bacterium and the host. We discuss a hypothetical scenario wherein H. pylori may have acquired virulence genes from donors within its environment that varied with change in human history and ecology. The H. pylori genomes sequenced to date portray fairly high abundance of such laterally acquired genes which have no assigned functions but could be linked to inflammatory responses or other pathogenic attributes. Therefore, the powerful virulence properties and survival strategies of Helicobacter make it a seasoned pathogen; thus the efforts to portray it as a commensal or a (harmless 'bacterial parasite' need rethinking.

[Helicobacter pylori population characteristic in patients with diseases of gastrointestinal tract].

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Zhebrun, A B; Svarval', A V; Balabash, O A; Ferman, R S

2013-01-01

Study H. pylori strains circulating in St. Petersburg among patients with various gastrointestinal tract pathology as well as study of frequency of infection by H. pylori based on serological markers data among this group of patients. By using serological method 162 individuals with various chronic diseases of stomach and duodenum were examined. The presence in blood serum of IgG against H. pylori bacterial antigen and IgG against its toxin--CagA was studied. 129 patients were examined bacteriologically, biopsy samples of stomach mucous membrane were studied. PCR in real time format was used for study of H. pylori strains (49) and biopsy samples (36) of stomach mucous membrane. The analysis performed showed that on the territory of St. Petersburg H. pylori strains containing cagA gene predominate (81.63% of the isolated strains). Genotyping of strains by vacA showed that s1m1 genotype was more frequent (in 57.14% of cases). The fraction of CagA positive strains in patients in St. Petersburg is maximum for stomach cancer (90.8%), whereas for peptic ulcer disease and gastritis it is 64.7% and 72.2%, respectively. In patients with stomach and duodenum pathology the parameters of seropositivity for H. pylori were significantly higher than in individuals without clinical manifestations of H. pylori infection (86.72% against 65.09%; p < 0.05). The data obtained on increase of fraction of CagA positive strains among H. pylori circulating in St. Petersburg determine the importance of conducting eradication H. pylori.

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Backert, Steffen

2011-11-01

Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA\\/B, SabA, AlpA\\/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA\\/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

Helicobacter pylori strains from a Nigerian cohort show divergent antibiotic resistance rates and a uniform pathogenicity profile.

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Ute Harrison

Full Text Available Antibiotic resistance in Helicobacter pylori is a factor preventing its successful eradication. Particularly in developing countries, resistance against commonly used antibiotics is widespread. Here, we present an epidemiological study from Nigeria with 111 isolates. We analyzed the associated disease outcome, and performed a detailed characterization of these isolated strains with respect to their antibiotic susceptibility and their virulence characteristics. Furthermore, statistical analysis was performed on microbiological data as well as patient information and the results of the gastroenterological examination. We found that the variability concerning the production of virulence factors between strains was minimal, with 96.4% of isolates being CagA-positive and 92.8% producing detectable VacA levels. In addition, high frequency of bacterial resistance was observed for metronidazole (99.1%, followed by amoxicillin (33.3%, clarithromycin (14.4% and tetracycline (4.5%. In conclusion, this study indicated that the infection rate of H. pylori infection within the cohort in the present study was surprisingly low (36.6%. Furthermore, an average gastric pathology was observed by histological grading and bacterial isolates showed a uniform pathogenicity profile while indicating divergent antibiotic resistance rates.

Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

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Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

2015-09-29

Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

Medicinal plant activity on Helicobacter pylori related diseases.

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Wang, Yuan-Chuen

2014-08-14

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

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease.

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Mahdi, Batool M

2011-03-01

Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 as compared with 30 healthy patients from a control group that was age and sex matched. Helicobacter pylori CagA+ was identified by an immunological test (Immunochromatography test) (ACON, USA). Helicobacter pyloriCagA+ was present in 42/60 (70%) of the patients with gastro-esophageal reflux disease and in 11/30 (36.6%) patients in the control group (p=0.002). The Odds ratio = 0.8004 with 95% Confidence Interval = from 0.3188 to 2.0094. The relative risk=1.35 that indicates an association between Helicobacter pylori and disease. The presence of Helicobacter pylori is significantly increased in patients with gastro-esophageal reflux disease as compared with the control group.

A Helicobacter pylori Homolog of Eukaryotic Flotillin Is Involved in Cholesterol Accumulation, Epithelial Cell Responses and Host Colonization

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Melanie L. Hutton

2017-06-01

Full Text Available The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as “lipid rafts.” Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248 with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01. HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05, and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05. Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.

Human gastric mucins differently regulate Helicobacter pylori proliferation, gene expression and interactions with host cells.

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Emma C Skoog

Full Text Available Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.

Helicobacter pylori the Latent Human Pathogen or an Ancestral Commensal Organism

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Jackie Li

2018-04-01

Full Text Available We dedicated this review to discuss Helicobacter pylori as one of the latest identified bacterial pathogens in humans and whether its role is mainly as a pathogen or a commensal. Diseases associated with this bacterium were highly prevalent during the 19th century and gradually have declined. Most diseases associated with H. pylori occurred in individuals older than 40 years of age. However, acquisition of H. pylori occurs mainly in young children inside the family setting. Prevalence and incidence of H. pylori has had a dramatic change in the last part of the 20th century and beginning of the 21th century. In developed countries there is a clear interruption of transmission and the lowest prevalence is observed in children younger than 10 years in these countries. A similar decline is observed but not at the same level in developing countries. Here we discuss the impact of the presence or absence of H. pylori in the health status of humans. We also discuss whether it is necessary or not to establish H. pylori eradication programs on light of the current decline in H. pylori prevalence.

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

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Santosh K. Tiwari

2011-01-01

Full Text Available 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.

Patrón de los motivos EPIYA de cepas cubanas de Helicobacter pylori positivas para CagA

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Lino E. Torres

2012-03-01

Conclusión. La mayoría de los aislamientos cubanos presentaron las combinaciones de motivos EPIYA menos virulentas (ABC. Los resultados del empleo de los nuevos cebadores y el análisis de la secuenciación, confirmaron que todas las cepas estudiadas portaban el gen cagA de tipo occidental. Ninguno de los patrones específicos de EPIYA se asoció con úlcera péptica. Este es el primer reporte que muestra la distribución de los motivos EPIYA en los aislamientos de H. pylori de la región del Caribe.   DOI: http://dx.doi.org/10.7705/biomedica.v32i1.453

Comparative Genomics of H. pylori and Non-Pylori Helicobacter Species to Identify New Regions Associated with Its Pathogenicity and Adaptability

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De-Min Cao

2016-01-01

Full Text Available 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.

Association of Helicobacter pylori infection with chronic atrophic gastritis: Meta-analyses according to type of disease definition.

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Weck, Melanie N; Brenner, Hermann

2008-08-15

Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG). A large variety of definitions of CAG have been used in epidemiologic studies in the past. The aim of this work was to systematically review and summarize estimates of the association between H. pylori infection and CAG according to the various definitions of CAG. Articles on the association between H. pylori infection and CAG published until July 2007 were identified. Separate meta-analyses were carried out for studies defining CAG based on gastroscopy with biopsy, serum pepsinogen I (PG I) only, the pepsinogen I/pepsinogen II ratio (PG I/PG II ratio) only, or a combination of PG I and the PG I/PG II ratio. Numbers of identified studies and summary odds ratios (OR) (95% confidence intervals) were as follows: gastroscopy with biopsy: n = 34, OR = 6.4 (4.0-10.1); PG I only: n = 13, OR = 0.9 (0.7-1.2); PG I/PG II ratio: n = 8, OR = 7.2 (3.1-16.8); combination of PG I and the PG I/PG II ratio: n = 20, OR = 5.7 (4.4-7.5). Studies with CAG definitions based on gastroscopy with biopsy or the PG I/PG II ratio (alone or in combination with PG I) yield similarly strong associations of H. pylori with CAG. The association is missed entirely in studies where CAG is defined by PG I only. (c) 2008 Wiley-Liss, Inc.

Helicobacter pylori and non-malignant diseases.

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Matysiak-Budnik, Tamara; Laszewicz, Wiktor; Lamarque, Dominique; Chaussade, Stanislas

2006-10-01

The prevalence of Helicobacter pylori-associated peptic ulcers, in particular duodenal ulcers, is decreasing following decreasing prevalence of H. pylori infection, while the frequency of non-steroidal anti-inflammatory drugs (NSAIDs)-induced and H. pylori-negative idiopathic ulcers is increasing. The incidence of bleeding ulcers has been stable during the last decades. Several putative H. pylori virulence genes, i.e., cag, vacA, babA, or dupA, as well as host-related genetic factors like IL-1beta and TNFalpha-gene polymorphism, have been proposed as risk factors for duodenal ulcer. H. pylori eradication may prevent NSAID complications, in particular, when it is performed before introduction of NSAIDs. There is a complex association between H. pylori and gastroesophageal reflux disease (GERD), and the impact of H. pylori eradication on the appearance of GERD symptoms depends on various host- and bacteria-related factors. Eradication of H. pylori in GERD is recommended in patients before instauration of a long-term PPI treatment to prevent the development of gastric atrophy. A small proportion (10%) of non-ulcer dyspepsia cases may be attributed to H. pylori and may benefit from eradication treatment. A test-and-treat strategy is more cost-effective than prompt endoscopy in the initial management of dyspepsia.

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

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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

Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults

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Brenner, H; Berg, Gabriele; Fröhlich, M

1999-01-01

It has been suggested that chronic infection with Helicobacter pylori (H. pylori), in particular infection with virulent strains producing the cytotoxin-associated protein CagA, may increase the risk of coronary heart disease by generation of a persistent low-grade inflammatory stimulus. We...... assessed the relation between serological markers of H. pylori infection and various markers of systemic inflammation in a population-based sample of 1834 men and women aged 18-88. A total of 39.3% of the sample had a positive IgG response, and among these a slight majority was CagA positive. Infection...... with H. pylori was unrelated to C-reactive protein and the leukocyte count, regardless of CagA status. There was an inverse relation between H. pylori infection and serum albumin. The adjusted OR (95% CI) of an albumin level in the bottom versus the top third were 2.2 (1.5-3.1) and 2.0 (1...

Virulence genes of Helicobacter pylori in gastritis, peptic ulcer and gastric cancer in Laos.

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Vannarath, Sengdao; Vilaichone, Ratha-korn; Rasachak, Bouachanh; Mairiang, Pisaln; Yamaoka, Yoshio; Shiota, Seiji; Binh, Tran Thanh; Mahachai, Varocha

2014-01-01

Helicobacter pylori (H. pylori) infection is an established cause of peptic ulcers and gastric cancer. The aim of this study was to identify H. pylori genotypes and to examine their associations with geographical regions and gastritis, peptic ulcers and gastric cancer in Laos. A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010--March 2012 were enrolled. Two biopsy specimens (one each from the antrum and corpus) were obtained for CLO testing and only CLO test-positive gastric tissue were used to extract DNA. PCR and sequencing were identified for variants of the cagA and vacA genotypes. Some 119 Laos patients (36.2%) were found to be infected with H. pylori including 83 with gastritis, 13 with gastric ulcers (GU), 20 with duodenal ulcers (DU) and 3 with gastric cancer. cagA was detected in 99.2%. East-Asian-type cagA (62%) and vacA s1c (64.7%) were predominant genotypes in Laos. vacA s1c-m1b was significantly higher in GU than gastritis (53.8% vs. 24.1%; P-value=0.04) whereas vacA s1a-m2 was significantly higher in DU than gastritis (40.0% vs. 16.9%; P-value=0.03). East-Asian-type cagA and vacA s1c were significantly higher in highland than lowland Lao (100% vs. 55.8%; P-value=0.001 and 88.2% vs. 61.5%, P-value=0.03 respectively). H. pylori is a common infection in Laos, as in other countries in Southeast Asia. The cagA gene was demonstrated in nearly all Laos patients, cagA and vacA genotypes being possible important factors in explaining H. pylori infection and disease outcomes in Laos.

Role of dupA in virulence of Helicobacter pylori.

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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.

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

OpenAIRE

Nakano, Masayuki; 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)?, a VacA receptor, reduced VacA-induced Src ph...

The co-evolved Helicobacter pylori and gastric cancer: trinity of bacterial virulence, host susceptibility and lifestyle

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Devi S Manjulata

2007-01-01

Full Text Available Abstract Helicobacter pylori is an important yet unproven etiological agent of gastric cancer. H. pylori infection is more prevalent in developing Asian countries like India and it is usually acquired at an early age. It has been two decades since Marshall and Warren (1984 first described curved bacilli in the stomach of ulcer and gastritis patients. This discovery has won them the Nobel Prize recently, but the debate whether H. pylori is a pathogen or a commensal organism is still hot. Associations with disease-specific factors remain illusive years after the genome sequences were made available. Cytotoxin-associated antigen A (CagA and the so-called plasticity region cluster genes are implicated in pathogenesis of the carcinoma of stomach. Another virulence factor VacA whose role is still debatable, has recently been projected in pathology of gastric cancer. Studies of the evolution through genetic variation in H. pylori populations have provided a window into the history of human population migrations and a possible co-evolution of this pathogen with its human host. Possible symbiotic relationships were seriously debated since the discovery of this pathogen. The debate has been further intensified as some studies proposed H. pylori infection to be beneficial in some humans. In this commentary, we attempt to briefly discuss about H. pylori as a human pathogen, and some of the important issues linked to its pathophysiology in different hosts. 'We dance around in a ring and suppose, the secret sits in the middle and knows' – Robert Frost

Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy.

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Sugimoto, Mitsushige; Yamaoka, Yoshio

2009-01-01

The cure rates of Helicobacter pylori infection by using a combination of a proton pump inhibitor (PPI) and antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of acid inhibition during the treatment. Currently used empirical triple therapies do not reliably produce a > or =80% cure rate on an intention-to-treat basis. Therefore, tailored regimens based on relevant microbiological findings and pharmacogenomics are recommended for attaining an acceptable > or =95% cure rate. Recently, virulence factors of H. pylori, such as cagA and vacA, are reported to be major factors determining the cure rates. Individuals infected with strains with cagA-negative and vacA s2 genotypes have significantly increased risk of eradication failure of H. pylori infection. These virulence factors enhance gastric mucosal inflammation and are associated with the development of peptic ulcer and gastric cancer. H. pylori virulence factors induce proinflammatory cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor (TNF)- which influence mucosal inflammation and/or gastric acid secretion. When physicians select an H. pylori eradication regimen with an acceptable cure rate, they might need to consider H. pylori virulence factors, especially cagA and vacA.

Helicobacter pylori virulence and cancer pathogenesis.

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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.

Pathobiology of Helicobacter pylori-induced Gastric Cancer

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Amieva, Manuel; Peek, Richard M.

2015-01-01

Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

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

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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…

Relationship between caga-positive Helicobacter pylori infection and risk of gastric cancer: a case control study in Porto Alegre, RS, Brazil

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Gilmara Coelho Meine

2011-03-01

Full Text Available CONTEXT: Gastric cancer is the second most common cause of cancer related death worldwide. Although Helicobacter pylori has been classified as a class I carcinogen, the presence of infection is not a factor that alone is able to lead to gastric cancer, and one of the possible explanations for this is the existence of different strains of H. pylori with different degrees of virulence. OBJECTIVES: To investigate the association between cagA-positive H. pylori and gastric cancer, using polymerase chain reaction (PCR for the detection of this bacterial strain. METHODS: Twenty-nine patients with gastric cancer were matched by sex and age (± 5 years with 58 patients without gastric cancer, submitted to upper gastrointestinal endoscopy. All patients were evaluated for the status of infection by H. pylori (through urease test, histological analysis and PCR for the genes ureA and 16SrRNA and by cagA-positive strain (through PCR for cagA gene. RESULTS: Evaluating the presence of infection by cagA-positive H. pylori, it was verified that the rate of infection was significantly higher in the group with gastric cancer when compared with the matched controls, occurring in 62.1% and 29.3%, respectively (OR = 3.95; CI 95% 1.543-10.096. CONCLUSIONS: There is an association between cagA-positive H. pylori strain and risk of gastric cancer.

Characteristics of clinical Helicobacter pylori strains from Ecuador.

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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.

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

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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

Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms.

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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.

Helicobacter pylori in Vegetables and Salads: Genotyping and Antimicrobial Resistance Properties

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Emad Yahaghi

2014-01-01

Full Text Available From a clinical and epidemiological perspective, it is important to know which genotypes and antibiotic resistance patterns are present in H. pylori strains isolated from salads and vegetables. Therefore, the present investigation was carried out to find this purpose. Three hundred eighty washed and unwashed vegetable samples and fifty commercial and traditional salad samples were collected from Isfahan, Iran. Samples were cultured and those found positive for H. pylori were analyzed using PCR. Antimicrobial susceptibility testing was performed using disk diffusion method. Seven out of 50 (14% salad and 52 out of 380 (13.68% vegetable samples harbored H. pylori. In addition, leek, lettuce, and cabbage were the most commonly contaminated samples (30%. The most prevalent virulence genes were oipA (86.44% and cagA (57.625. VacA s1a (37.28% and iceA1 (47.45% were the most prevalent genotypes. Forty different genotypic combinations were recognized. S1a/cagA+/iceA1/oipA+ (33.89%, s1a/cagA+/iceA2/oipA (30.50%, and m1a/cagA+/iceA1/oipA+ (28.81% were the most prevalent combined genotypes. Bacterial strains had the highest levels of resistance against metronidazole (77.96%, amoxicillin (67.79%, and ampicillin (61.01%. High similarity in the genotyping pattern of H. pylori among vegetable and salad samples and human specimens suggests that vegetable and salads may be the sources of the bacteria.

Roles of the plasticity regions of Helicobacter pylori in gastroduodenal pathogenesis.

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Yamaoka, Yoshio

2008-05-01

Putative virulence genes of Helicobacter pylori are generally classified into three categories: strain-specific genes, phase-variable genes and genes with variable structures/genotypes. Among these, there has recently been considerable interest in strain-specific genes found outside of the cag pathogenicity island, especially genes in the plasticity regions. Nearly half of the strain-specific genes of H. pylori are located in the plasticity regions in strains 26695 and J99. Strain HPAG1, however, seems to lack a typical plasticity region; instead it has 43 HPAG1-specific genes which are either undetectable or incompletely represented in the genomes of strains 26695 and J99. Recent studies showed that certain genes or combination of genes in this region may play important roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. Most previous studies have focused on the plasticity region in strain J99 (jhp0914-jhp0961) and the jhp0947 gene and the duodenal ulcer promoting (dupA) gene are good candidate markers for gastroduodenal diseases although there are some paradoxical findings. The jhp0947 gene is reported to be associated with an increased risk of both duodenal ulcers and gastric cancers, whereas the dupA gene, which encompasses jhp0917 and jhp0918, is reported to be associated with an increased risk of duodenal ulcers and protection against gastric cancers. In addition, recent studies showed that approximately 10-30 % of clinical isolates possess a 16.3 kb type IV secretion apparatus (tfs3) in the plasticity region. Studies on the plasticity region have only just begun, and further investigation is necessary to elucidate the roles of genes in this region in gastroduodenal pathogenesis.

Relationship between childhood asthma and Helicobacter pylori infection

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Ying Wu

2016-07-01

Full Text Available Objective: To investigate the correlation between childhood asthma and Helicobacter pylori infection. Methods: A total of 80 children with asthma who were treated in our hospital from May 2012 to May 2015 were selected as the research subjects, and 40 cases of healthy children were selected as control group, the Helicobacter pylori infection of the two groups of patients were compared, the double antibody sandwich enzyme-linked immunosorbent assay was used to detect the serum Helicobacter pylori-IgG, Helicobacter pylori-CagAIgG, IL-4, Helicobacter pylori, IFN-γ and IL-1β, etc., and the correlation between Helicobacter pylori infection and asthma was analyzed. Results: The positive rates of Helicobacter pylori infection in asthma group and children in attack stage were significantly higher than those in control group and children in remission stage (P<0.05. The positive rates of serum Helicobacter pylori-IgG and Helicobacter pylori-CagAIgG in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage (P<0.05. The serum levels of IFN-γ in asthma group and children in attack stage were significantly lower than those in control group and children in remission stage, IL-4 and IL-1β levels in the former were significantly higher than those in the latter (P<0.05. Helicobacter pylori infection positive had significant positive correlation with IL-1β concentration (r=0.75, P<0.05. Conclusions: Helicobacter pylori infection in children has significant positive correlation with the incidence of asthma, suggesting that Helicobacter pylori infection has a certain protective effect on childhood asthma, but persistent Helicobacter pylori infection in children with asthma can aggravate the immune disorder, which is the main reason for the difficulty of treatment of asthma.

Seroepidemiology of the Helicobacter pylori infection among people of Pishva city of Varamin

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Maryam Abdi

2014-12-01

Full Text Available Background and Aim: The epidemiologic pattern of Helicobacter pylori infection is differed between developed countries and developing countries, and also it is depend on the total standard of living in each region. At the present study, the seroprevalence of H.pylori infection and effectiveness of underlying factors in prevalence of this infection among residents of Pishva city of Varamin was evaluated. Materials and Methods: This descriptive study was conducted after completion the questionnaire. The peripheral blood of 314 people without any confirmed gastric problem were collected. Then, the titer of total IgG and IgG anti CagA of H. pylori was evaluated by ELISA method. Consequently, the correlation between serologic data and different factors were analyzed by SPSS statistical software. Results: The existence of total IgG was detected in 164 (55.2% of 314 patients and was negative in 130 people (41.4%.Also, the IgG anti CagA were positive in 46 (29.1%, it was negative in 105 people (66.5% and the rested were in borderline. There was statistical meaningful correlation between positive result of serology test of IgG anti CagA to  some risk factors such as age, the number of the member of family, the educational status and occupation, the consumption of can, heart diseases, the rate of cholesterol, the history of gastrointestinal symptoms,  heartburn and reflux (P <0.05 . Conclusions: With regard to high prevalence of H. pylori in this area (55.2% and its presumptive effect in infected people, the necessary of hygiene education and precise control of infection is suggested.

Pathogenicity island mobility and gene content.

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Williams, Kelly Porter

2013-10-01

Key goals towards national biosecurity include methods for analyzing pathogens, predicting their emergence, and developing countermeasures. These goals are served by studying bacterial genes that promote pathogenicity and the pathogenicity islands that mobilize them. Cyberinfrastructure promoting an island database advances this field and enables deeper bioinformatic analysis that may identify novel pathogenicity genes. New automated methods and rich visualizations were developed for identifying pathogenicity islands, based on the principle that islands occur sporadically among closely related strains. The chromosomally-ordered pan-genome organizes all genes from a clade of strains; gaps in this visualization indicate islands, and decorations of the gene matrix facilitate exploration of island gene functions. A %E2%80%9Clearned phyloblocks%E2%80%9D method was developed for automated island identification, that trains on the phylogenetic patterns of islands identified by other methods. Learned phyloblocks better defined termini of previously identified islands in multidrug-resistant Klebsiella pneumoniae ATCC BAA-2146, and found its only antibiotic resistance island.

Association between infection with Helicobacter pylori and atopy in young Ethiopian children: A longitudinal study.

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Taye, B; Enquselassie, F; Tsegaye, A; Amberbir, A; Medhin, G; Fogarty, A; Robinson, K; Davey, G

2017-10-01

Epidemiological evidence from developed countries indicates that Helicobacter pylori infection correlates with a reduced risk of atopy and allergic disorders; however, limited data are available from low-income countries. We examined associations between H. pylori infection in early childhood and atopy and reported allergic disorders at the age of 6.5 years in an Ethiopian birth cohort. A total of 856 children (85.1% of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half years. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Questions on allergic disease symptoms were based on the International Study of Asthma and Allergies in Children (ISAAC) core allergy and environmental questionnaire. Serum samples were analysed for total IgE levels and anti-H. pylori cytotoxin-associated gene A (CagA) IgG antibody using commercially available ELISA kits. Stool samples were analysed for H. pylori antigen using a rapid immunochromatographic test. The independent effects of H. pylori infection (measured at age of 3, 5 and 6.5 years) on prevalence and incidence of atopy and reported allergic disorders (measured at age of 6.5 years) were determined using multiple logistic regression. In cross-sectional analysis, current H. pylori infection at age 6.5 years was inversely, though not significantly, related to prevalence of atopy and "any allergic condition" at age 6.5 years. However, detection of H. pylori infection at any point up to age 6.5 years was associated with a significantly reduced odds of both atopy and "any allergic condition" (adjusted OR AOR, 95% CI, 0.54; 0.32-0.92, P = .02, and .31; 0.10-0.94, P = .04, respectively). In longitudinal analyses, H. pylori infection at age 3 was inversely associated with incidence of atopy (AOR, 95% CI, 0.49; 0.27-0.89, P = .02). Furthermore, among H. pylori-infected children, those with a Cag

Responsiveness to acidity via metal ion regulators mediates virulence in the gastric pathogen Helicobacter pylori.

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Bury-Moné, Stéphanie; Thiberge, Jean-Michel; Contreras, Monica; Maitournam, Aboubakar; Labigne, Agnès; De Reuse, Hilde

2004-07-01

The virulence of pathogenic bacteria is dependent on their adaptation to and survival in the stressful conditions encountered in their hosts. Helicobacter pylori exclusively colonizes the acid stomach of primates, making it an ideal study model. Little is known about how H. pylori responds to the moderately acidic conditions encountered at its colonization site, the gastric mucus layer. Thus, we compared gene expression profiles of H. pylori 26695 grown at neutral and acidic pH, and validated the data for a selection of genes by real-time polymerase chain reaction, dot-blots or enzymatic assays. During growth in acidic conditions, 56 genes were upregulated and 45 genes downregulated. We found that acidity is a signal modulating the expression of several virulence factors. Regulation of genes related to metal ion homeostasis suggests protective mechanisms involving diminished transport and enhanced storage. Genes encoding subunits of the F0F1 ATPase and of a newly identified Na+/H+ antiporter (NhaC-HP0946) were downregulated, revealing that this bacterium uses original mechanisms to control proton entry. Five of the upregulated genes encoded proteins controlling intracellular ammonia synthesis, including urease, amidase and formamidase, underlining the major role of this buffering compound in the protection against acidity in H. pylori. Regulatory networks and transcriptome analysis as well as enzymatic assays implicated two metal-responsive transcriptional regulators (NikR and Fur) and an essential two-component response regulator (HP0166, OmpR-like) as effectors of the H. pylori acid response. Finally, a nikR-fur mutant is attenuated in the mouse model, emphasizing the link between response to acidity, metal metabolism and virulence in this gastric pathogen.

Molecular Epidemiology of Helicobacter pylori Infection in a Minor Ethnic Group of Vietnam: A Multiethnic, Population-Based Study.

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Binh, Tran Thanh; Tuan, Vo Phuoc; Dung, Ho Dang Quy; Tung, Pham Huu; Tri, Tran Dinh; Thuan, Ngo Phuong Minh; Tam, Le Quang; Nam, Bui Chi; Giang, Do Anh; Hoan, Phan Quoc; Uchida, Tomohisa; Trang, Tran Thi Huyen; Khien, Vu Van; Yamaoka, Yoshio

2018-03-01

The Helicobacter pylori -induced burden of gastric cancer varies based on geographical regions and ethnic grouping. Vietnam is a multiethnic country with the highest incidence of gastric cancer in Southeast Asia, but previous studies focused only on the Kinh ethnic group. A population-based cross-sectional study was conducted using 494 volunteers (18-78 years old), from 13 ethnic groups in Daklak and Lao Cai provinces, Vietnam. H. pylori status was determined by multiple tests (rapid urease test, culture, histology, and serology). cagA and vacA genotypes were determined by PCR-based sequencing. The overall H. pylori infection rate was 38.1%. Multivariate analysis showed that variations in geographical region, age, and ethnicity were independent factors associated with the risk of H. pylori acquisition. Therefore, multicenter, multiethnic, population based study is essential to assess the H. pylori prevalence and its burden in the general population. Only the E De ethnicity carried strains with Western-type CagA (82%) and exhibited significantly lower gastric mucosal inflammation compared to other ethnic groups. However, the histological scores of Western-type CagA and East-Asian-type CagA within the E De group showed no significant differences. Thus, in addition to bacterial virulence factors, host factors are likely to be important determinants for gastric mucosal inflammation and contribute to the Asian enigma.

Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

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Sandra Mendoza Elizalde

2016-11-01

Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

ROLE OF HELICOBACTER PYLORI INFECTION AND LIFESTYLE HABITS IN THE DEVELOPMENT OF GASTRODUODENAL DISEASES IN A POPULATION FROM THE BRAZILIAN AMAZON

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Ruth Maria Dias Ferreira VINAGRE

2013-09-01

Full Text Available Context Although more than half of the world's population is colonized with Helicobacter pylori, it remains unknown why this organism is able to produce severe disease in some hosts and be innocuous in others. The clinical outcome of infection is determined by several factors, including differences in the host response to bacterial stimulation, specific virulence factors of the organism and environmental influences, or a combination of these factors. Objectives This study compared the prevalence of H. pylori infection and risk factors (infection with CagA+ strains, excessive alcohol consumption, smoking, and inadequate eating habits between patients with different gastrointestinal disorders and associated these risk factors with the histopathological findings. Methods In a prospective study, samples were collected from 442 patients and a standardized questionnaire regarding lifestyle habits (excessive alcohol consumption, smoking, and eating habits was applied. The presence of H. pylori and of the cagA gene was investigated by polymerase chain reaction (PCR. Gastric biopsies were obtained for histological assessment. Results The frequency of alcohol consumption, smoking, inadequate diet and infection with CagA+ H. pylori was higher among patients with peptic ulcer and adenocarcinoma when compared to those with gastritis. Gastric inflammation was more pronounced in patients infected with CagA+ strains. Conclusion We conclude that infection with CagA+ H. pylori strains, excessive alcohol consumption, smoking and inadequate eating habits increase the risk of developing peptic ulcer and gastric carcinoma.

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

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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. © 2015 John Wiley & Sons Ltd.

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

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

2015-01-01

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. PMID:25728540

Helicobacter pylori infection and serum ferritin

DEFF Research Database (Denmark)

Berg, Gabriele; Bode, G; Blettner, M

2001-01-01

OBJECTIVE: Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of non-hem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin...... in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot. RESULTS: In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study...... were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 microg/dl among H. pylori-infected compared with 63.8 microg/dl among uninfected persons. A multiple linear regression model with log...

Frequency of virulence genes in mixed infections with Helicobacter pylori strains from a Mexican population

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R. González-Vázquez

2016-01-01

Conclusions: The Fisher's exact test did not support a significant association between clinical outcome and genotype. The main circulating genotypes in the Mexican population studied were: cagA+, vacAs1, and vacAm1. Multiplex PCR can be used as a screening test for H. pylori strains. Furthermore, the cagE gene is a good marker for identifying cag-PAI positive strains.

Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

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Yuichi Matsuo

2017-03-01

Full Text Available 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.

Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country

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Almeida, N; Donato, MM; Romãozinho, JM; Luxo, C; Cardoso, O; Cipriano, MA; Marinho, C; Fernandes, A; Sofia, C

2015-01-01

BACKGROUND: Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial-associated virulence factors. AIM: This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. METHODS: This prospective study involved 148 infected patients (110 female; mean age 43.5 ± 13.4...

The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers

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Choi Sang-Wook

2010-11-01

Full Text Available Abstract Background The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with Helicobacter pylori (H. pylori and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements. Methods The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the H. pylori-negative gastric mucosa. Results The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the H. pylori-positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the H. pylori-positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner. Conclusions The overmethylated genes under the influence of retroelement methylation in the H. pylori-infected stomach are demethylated in the gastric cancers influenced by LOH.

Validation of a Novel Immunoline Assay for Patient Stratification according to Virulence of the Infecting Helicobacter pylori Strain and Eradication Status

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Luca Formichella

2017-01-01

Full Text Available Helicobacter pylori infection shows a worldwide prevalence of around 50%. However, only a minority of infected individuals develop clinical symptoms or diseases. The presence of H. pylori virulence factors, such as CagA and VacA, has been associated with disease development, but assessment of virulence factor presence requires gastric biopsies. Here, we evaluate the H. pylori recomLine test for risk stratification of infected patients by comparing the test score and immune recognition of type I or type II strains defined by the virulence factors CagA, VacA, GroEL, UreA, HcpC, and gGT with patient’s disease status according to histology. Moreover, the immune responses of eradicated individuals from two different populations were analysed. Their immune response frequencies and intensities against all antigens except CagA declined below the detection limit. CagA was particularly long lasting in both independent populations. An isolated CagA band often represents past eradication with a likelihood of 88.7%. In addition, a high recomLine score was significantly associated with high-grade gastritis, atrophy, intestinal metaplasia, and gastric cancer. Thus, the recomLine is a sensitive and specific noninvasive test for detecting serum responses against H. pylori in actively infected and eradicated individuals. Moreover, it allows stratifying patients according to their disease state.

Elevated interleukin-32 expression is associated with Helicobacter pylori-related gastritis.

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Liu-Sheng Peng

Full Text Available BACKGROUND: Interleukin-32 (IL-32 is a recently discovered proinflammatory cytokine involved in inflammatory diseases. We investigated the expression of IL-32 and its regulation mechanism in the inflammatory response of patients with Helicobacter pylori (H. pylori infection. DESIGN AND METHODS: IL-32 mRNA and protein expression in gastric tissues was detected by quantitative real-time PCR and immunohistochemistry. The regulation of IL-32 in human gastric epithelia cell line AGS was investigated by different cytokine stimulation and different H. pylori strain infection. RESULTS: Gastric IL-32 mRNA and protein expression were elevated in patients with H. pylori infection and positively correlated with gastritis. In H. pylori-infected patients, the mRNA level of IL-32 was also correlated with that of proinflammatory cytokines IL-1β and TNF-α. In vitro IL-1β and TNF-α could upregulate IL-32 mRNA and protein level in AGS cells, which was dependent on NF-κB signal pathway. The regulation of IL-32 expression in response to H. pylori-infection could be weakened by using neutralizing antibodies to block IL-1β and TNF-α. Moreover, H. pylori-infected AGS cells also induced IL-32 mRNA and protein expression, which was dependent on CagA. CONCLUSIONS: IL-32 level is elevated in patients with H. pylori infection and its expression is regulated by proinflammatory stimuli, suggesting that IL-32 may play a role in the pathogenesis of H. pylori-related gastritis.

Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL Expression in Gastric Mucosa Infected with Helicobacter pylori

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Fen Wang

2015-01-01

Full Text Available Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1, tumor necrosis factor receptor superfamily member 9 (4-1BB, and B-cell lymphoma-extra large (Bcl-xL in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM patients, and 28 gastric carcinoma (Ca patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P<0.05 compared with CG. There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P<0.05. Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P<0.05. Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue.

Helicobacter pylori virulence factors in development of gastric carcinoma.

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Wang, Ming-Yi; Liu, Xiao-Fei; Gao, Xiao-Zhong

2015-01-01

Helicobacter pylori plays a vital role in the pathogenesis of gastric carcinoma. However, only a relatively small proportion of individuals infected with H. pylori develop gastric carcinoma. Differences in the incidence of gastric carcinoma among infected individuals can be explained, at least partly, by the different genotypes of H. pylori virulence factors. Thus far, many virulence factors of H. pylori, such as Cag PAI, VacA, OMPs and DupA, have been reported to be involved in the development of gastric cancer. The risk of developing gastric cancer during H. pylori infection is affected by specific host-microbe interactions that are independent of H. pylori virulence factors. In this review, we discuss virulence factors of H. pylori and their role in the development of gastric carcinoma that will provide further understanding of the biological interactions of H. pylori with the host.

Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution.

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Kumar, Narender; Mariappan, Vanitha; Baddam, Ramani; Lankapalli, Aditya K; Shaik, Sabiha; Goh, Khean-Lee; Loke, Mun Fai; Perkins, Tim; Benghezal, Mohammed; Hasnain, Seyed E; Vadivelu, Jamuna; Marshall, Barry J; Ahmed, Niyaz

2015-01-01

The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Helicobacter pylori-induced IL-33 modulates mast cell responses, benefits bacterial growth, and contributes to gastritis.

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Lv, Yi-Pin; Teng, Yong-Sheng; Mao, Fang-Yuan; Peng, Liu-Sheng; Zhang, Jin-Yu; Cheng, Ping; Liu, Yu-Gang; Kong, Hui; Wang, Ting-Ting; Wu, Xiao-Long; Hao, Chuan-Jie; Chen, Weisan; Yang, Shi-Ming; Zhao, Yong-Liang; Han, Bin; Ma, Qiang; Zou, Quan-Ming; Zhuang, Yuan

2018-04-25

Interleukin (IL)-induced inflammatory responses are critical for the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. IL-33 represents a recently discovered proinflammatory cytokine involved in inflammatory diseases, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric IL-33 mRNA and protein expression were elevated in gastric mucosa of both patients and mice infected with H. pylori, which is positively correlated with bacterial load and the degree of gastritis. IL-33 production was promoted via extracellular regulated protein kinases (ERK) signaling pathway activation by gastric epithelial cells in a cagA-dependent manner during H. pylori infection, and resulted in increased inflammation and bacteria burden within the gastric mucosa. Gastric epithelial cell-derived IL-33 promoted TNF-α production from mast cells in vitro, and IL-33 increased TNF-α production in vivo. Increased TNF-α inhibited gastric epithelial cell proliferation, conducing to the progress of H. pylori-associated gastritis and bacteria colonization. This study defined a patent regulatory networks involving H. pylori, gastric epithelial cell, IL-33, mast cell, and TNF-α, which jointly play a pathological effect within the gastric circumstances. It may be a valuable strategy to restrain this IL-33-dependent pathway in the treatment of H. pylori-associated gastritis.

Helicobacter pylori infection in women with Hashimoto thyroiditis

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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 thyroid malfunction was independently associated with an increased risk of HT (odds ratio 3.39, 95% confidence interval 1.86–6.18, P thyroid malfunction is a risk factor for HT. PMID:27442635

Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

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Pachathundikandi, Suneesh Kumar; Tegtmeyer, Nicole; Backert, Steffen

2013-01-01

Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α5β1 receptor. Other targeted membrane-based receptors include the integrins αvβ3, αvβ5, and β2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed. PMID:24280762

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

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Lee, Inchul

2014-06-07

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

Association of the Helicobacter pylori cagA, vacA, and iceA genotypes with chronic follicular gastritis in a Colombian population at high risk for gastric cancer.

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Carlosama-Rosero, Y H; Bolaños-Bravo, H; Sierra-Tórres, C H; Rosero, E A

2018-05-16

Follicular gastritis is associated with Helicobacter pylori infection, but little is known of its relation to bacterial genotypes. Our aim was to establish the relation between follicular gastritis and different H. pylori strains. An analytic case-control study was conducted that included 36 patients with follicular gastritis (cases) and 83 with nonatrophic gastritis (controls). The sociodemographic information was obtained through a questionnaire. Biopsies were evaluated according to the Sydney System and the Wotherspoon scoring system. Helicobacter pylori genotyping was performed using the polymerase chain reaction technique. The quantitative variables were presented as mean and standard deviation and the qualitative variables as proportions and absolute frequency. The effect of each variable on outcome (follicular gastritis) was evaluated through the odds ratio and its 95% confidence interval. Statistical significance was set at a P<.05. Follicular gastritis was associated with Helicobacter pylori infection (OR: 13.41, CI: 1.7-103, P=.01). The CagA+ genotype was present in 56.5% of the cases and 58% of the controls. The cytotoxic VacAs1m1strain was present in 82% of the isolates in both groups. IceA1 frequency was 34.8% in the cases and 26% in the controls and the difference was not statistically significant. The population studied had elevated frequencies of cytotoxic Helicobacter pylori strains and the iceA1 genotype was more frequent in follicular gastritis. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

The role of environmental tobacco exposure and Helicobacter pylori infection in the risk of chronic tonsillitis in children

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Chen Li’e

Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Helicobacter pylori (H. pylori is a chronic infectious pathogen with high prevalence. This study investigated the interaction between environmental tobacco exposure and H. pylori infection on the incidence of chronic tonsillitis in Chinese children. DESIGN AND SETTING: Cross-sectional study performed in an outpatient clinic in China. METHODS: Pediatric patients with chronic tonsillitis were enrolled. H. pylori infection was determined according to the presence of H. pylori CagA IgG antibodies. Serum cotinine levels and environmental tobacco smoke (ETS exposure were determined for all participants. RESULTS: There was no significant difference in H. pylori infection between the children with chronic tonsillitis and children free of disease, but there was a significant difference in ETS between the two groups (P = 0.011. We next studied the association between ETS and chronic tonsillitis based on H. pylori infection status. In the patients with H. pylori infection, there was a significant difference in ETS distribution between the chronic tonsillitis and control groups (P = 0.022. Taking the participants without ETS as the reference, multivariate logistic regression analysis showed that those with high ETS had higher susceptibility to chronic tonsillitis (adjusted OR = 2.33; 95% CI: 1.67-3.25; adjusted P < 0.001. However, among those without H. pylori infection, ETS did not predispose towards chronic tonsillitis. CONCLUSION: Our findings suggest that tobacco exposure should be a putative mediator risk factor to chronic tonsillitis among children with H. pylori infection.

Performance of a Multiplex Serological Helicobacter pylori Assay on a Novel Microfluidic Assay Platform

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Angela Filomena

2017-10-01

Full Text Available Infection with Helicobacter pylori (H. pylori occurs in 50% of the world population, and is associated with the development of ulcer and gastric cancer. Serological diagnostic tests indicate an H. pylori infection by detecting antibodies directed against H. pylori proteins. In addition to line blots, multiplex assay platforms provide smart solutions for the simultaneous analysis of antibody responses towards several H. pylori proteins. We used seven H. pylori proteins (FliD, gGT, GroEL, HpaA, CagA, VacA, and HP0231 and an H. pylori lysate for the development of a multiplex serological assay on a novel microfluidic platform. The reaction limited binding regime in the microfluidic channels allows for a short incubation time of 35 min. The developed assay showed very high sensitivity (99% and specificity (100%. Besides sensitivity and specificity, the technical validation (intra-assay CV = 3.7 ± 1.2% and inter-assay CV = 5.5 ± 1.2% demonstrates that our assay is also a robust tool for the analysis of the H. pylori-specific antibody response. The integration of the virulence factors CagA and VacA allow for the assessment of the risk for gastric cancer development. The short assay time and the performance of the platform shows the potential for implementation of such assays in a clinical setting.

Helicobacter pylori virulence factors and their role in peptic ulcer diseases in Turkey.

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Tuncel, I E; Hussein, N R; Bolek, B K; Arikan, S; Salih, B A

2010-01-01

The role of virulence factors present in Helicobacter pylori (H. pylori) strains and the characterization of such factors being predictive of specific disease is still not clear. In this study, the cagA, vacA alleles and the recently characterized vacA i-region and dupA and their association with the severity of the disease was determined. Antral biopsies from 91patients with peptic ulcer (PU) (n = 41), gastritis (n = 48) and gastric cancer (GC) (n = 2) were analyzed for the presence of H. pylori by the CLO-test and PCR. A 79/91 (86%) patients were positive for H. pylori by either PCR or by both PCR and CLO-test. PCR-based typing of H. pylori isolates was performed on DNA extracted directly from biopsy samples. The cagA+ strains were found more likely to be associated with vacA s1 than s2. The vacA i1 allele detected in 16/23 (70%) of samples had significant association with duodenal ulcers than those 16/37 (44%) of gastritis (P dupA and duodenal ulcer. This study provided more evidence that the vacA i1 allele is one of the virulence factors of H. pylori that had significant association with severe outcome.

Expression, purification, crystallization and preliminary X-ray analysis of an NAD-dependent glyceraldehyde-3-phosphate dehydrogenase from Helicobacter pylori

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Elliott, Paul R.; Mohammad, Shabaz; Melrose, Helen J.; Moody, Peter C. E., E-mail: pcem1@leicester.ac.uk [Henry Wellcome Laboratories for Structural Biology, University of Leicester, Leicester LE1 9HN (United Kingdom)

2008-08-01

Glyceraldehyde-3-phosphate dehydrogenase B from H. pylori has been cloned, expressed, purified and crystallized in the presence of NAD. Crystals of GAPDHB diffracted to 2.8 Å resolution and belonged to space group P6{sub 5}22, with unit-cell parameters a = b = 166.1, c = 253.1 Å. Helicobacter pylori is a dangerous human pathogen that resides in the upper gastrointestinal tract. Little is known about its metabolism and with the onset of antibiotic resistance new treatments are required. In this study, the expression, purification, crystallization and preliminary X-ray diffraction of an NAD-dependent glyceraldehyde-3-phosphate dehydrogenase from H. pylori are reported.

Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection.

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Yoshikazu Furuta

Full Text Available Helicobacter pylori, a bacterial pathogen that can infect human stomach causing gastritis, ulcers and cancer, is known to have a high degree of genome/epigenome diversity as the result of mutation and recombination. The bacteria often infect in childhood and persist for the life of the host. One of the reasons of the rapid evolution of H. pylori is that it changes its genome drastically for adaptation to a new host. To investigate microevolution and adaptation of the H. pylori genome, we undertook whole genome sequencing of the same or very similar sequence type in multi-locus sequence typing (MLST with seven genes in members of the same family consisting of parents and children in Japan. Detection of nucleotide substitutions revealed likely transmission pathways involving children. Nonsynonymous (amino acid changing mutations were found in virulence-related genes (cag genes, vacA, hcpDX, tnfα, ggt, htrA and the collagenase gene, outer membrane protein (OMP genes and other cell surface-related protein genes, signal transduction genes and restriction-modification genes. We reconstructed various pathways by which H. pylori can adapt to a new human host, and our results raised the possibility that the mutational changes in virulence-related genes have a role in adaptation to a child host. Changes in restriction-modification genes might remodel the methylome and transcriptome to help adaptation. This study has provided insights into H. pylori transmission and virulence and has implications for basic research as well as clinical practice.

Detection of Helicobacter pylori vacA, cagA and iceA1 virulence ...

African Journals Online (AJOL)

Background: Helicobactor pylori (H. pylori) virulence markers would be useful to predict peptic ulcer disease (PUD) or gastric cancer. Aim: In Egypt, since inadequate data are present regarding H. pylori virulence–related genes in different age group patients with gastro-duodenal diseases, it becomes crucial to study the ...

Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: A ten-year follow-up of the ESTHER cohort study.

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Chen, Xin-Zu; Schöttker, Ben; Castro, Felipe Andres; Chen, Hongda; Zhang, Yan; Holleczek, Bernd; Brenner, Hermann

2016-03-29

To assess the association of H. pylori and chronic atrophic gastritis (AG) with colonic, pancreatic and gastric cancer in a population-based prospective cohort. Serum antibodies against H. pylori in general and specific to cytotoxin-associated gene A (CagA), as well as serum pepsinogen I and II were analyzed in 9,506 men and women, aged 50-75 years in a cohort study from Saarland, Germany. Incident cases of colonic, pancreatic and gastric cancer were ascertained by record linkage with data from the Saarland Cancer Registry. During an average follow-up of 10.6 years, 108 colonic, 46 pancreatic and 27 gastric incident cancers were recorded. There was no association between H. pylori infection and colonic cancer (HR = 1.07; 95% CI 0.73-1.56) or pancreatic cancer (HR = 1.32; 0.73-2.39), regardless of either CagA seropositivity or AG status. In contrast, CagA+ infection was associated with a strongly increased risk of gastric cancer, especially non-cardia gastric cancer, and this association was particularly pronounced in the presence of AG. Compared to people without AG and without CagA+ infection, people with both risk factors had a significantly increased risk of non-cardia gastric cancer (HR = 32.4; 7.6-137.6). This large cohort study did not observe an association of H. pylori infection or AG with colonic or pancreatic cancer, but underlines that the vast majority of non-cardia gastric cancers arise from AG and infection with CagA+ H. pylori strains.

A single nucleotide change affects fur-dependent regulation of sodB in H. pylori.

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Beth M Carpenter

Full Text Available Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur in the absence of iron (apo-Fur regulation [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter.

Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to gastric adenocarcinoma cells

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Tharmalingam, Nagendran; Kim, Sa-Hyun; Park, Min; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong Bae

2014-01-01

Background Piperine is a compound comprising 5-9% of black pepper (Piper nigrum), which has a variety of biological roles related to anticancer activities. Helicobacter pylori has been classified as a gastric carcinogen, because it causes gastritis and gastric cancer by injecting the virulent toxin CagA and translocating VacA. The present study investigated the inhibitory action of piperine on H. pylori growth and adhesion. Methods Inhibition of H. pylori growth was determined by the broth ma...

The dynamics of heat shock system activation in Monomac-6 cells upon Helicobacter pylori infection.

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Pierzchalski, P; Jastrzebska, M; Link-Lenczowski, P; Leja-Szpak, A; Bonior, J; Jaworek, J; Okon, K; Wojcik, P

2014-12-01

Immune system cells, particularly phagocytes, are exposed to direct contact with pathogens. Because of its nature - elimination of pathogenes - their cytoprotective systems supposed to be quick and forceful. Physiological consequence of phagocytosis for the phagocyte is the apoptotic death to prevent the eventual survival of bacteria as intracellular parasites. However, in some cases, defense systems used by the bacteria force the immune cells to prolong the contact with the pathogen for its effective elimination. Experiments were performed on Monomac-6 cells exposed to live CagA, VacA expressing Helicobacter pylori (H. pylori) over different period of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polymerase chain reaction, Western-blot and electrophoretic mobility shift assay, respectively. We found that Monomac-6 cells infection with H. pylori resulted in the translocation of the entire cellular content of the heat shock protein 70 (HSP70) into the cytoplasm, where its presence could protect cell against toxic products of engulfed bacteria and premature apoptosis. At the same time the nuclear translocation of heat shock factor 1 (HSF-1) and activation of HSP70 gene transcription was noticed. Action of HSP70 might to postpone monocyte apoptosis through protecting cytoplasmic and nuclear proteins from damaging effect of bacterial products, what could be the defending mechanism against the toxic stress caused by engulfed bacteria and provide the immune cell with the sufficient amount of time required for neutralization of the bacteria from phagosomes, even at the expense of temporary lack of the protection of nuclear proteins.

Differences in virulence markers between Helicobacter pylori strains from Iraq and those from Iran: potential importance of regional differences in H. pylori-associated disease.

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Hussein, Nawfal R; Mohammadi, Marjan; Talebkhan, Yeganeh; Doraghi, Masoumeh; Letley, Darren P; Muhammad, Merdan K; Argent, Richard H; Atherton, John C

2008-05-01

Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma; the latter is common in Iran but not in Iraq. We hypothesized that more virulent H. pylori strains may be found in Iran than in Iraq and so compared established and newly described virulence factors in strains from these countries. We studied 59 unselected dyspeptic patients from Iran and 49 from Iraq. cagA was found in similar proportions of strains from both countries (76% in Iran versus 71% in Iraq) and was significantly associated with peptic ulcer disease in Iraq (P dupA was found in similar proportions of Iranian and Iraqi strains (38% and 32%, respectively) and was associated with peptic ulceration in Iraqi patients (P pylori strains from Iraq and Iran possess virulence factors similar to those in Western countries. The presence of cagA with more phosphorylation motifs in Iranian strains may contribute to the higher incidence of gastric cancer. However, the association between strain virulence markers and disease in Iraq but not Iran suggests that other host and environmental factors may be more important in the disease-prone Iranian population.

Normalization of pH level and gastric mucosa after eradication of H. pylori in the remnant stomach.

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Kato, Shunji; Matsukura, Norio; Matsuda, Noriko; Tsuchiya, Shinichi; Naito, Zenya; Tajiri, Takashi

2008-12-01

The Updated Sydney System (USS) is used to evaluate chronic gastritis and chronic atrophic gastritis (CAG) due to H. pylori infection. Here, we investigated USS scores and gastric juice pH levels in H. pylori infection-positive or -eradicated patients with remnant stomach after surgery. Gastric juice pH levels were measured using pH test-tape in 197 patients (112 H. pylori-positive and 85 H. pylori-negative after eradication) who had undergone distal gastrectomy and conventional H. pylori eradication therapy. In H. pylori infection-positive remnant stomach cases, gastric juice pH showed a reverse correlation with pepsinogen I/II ratio, and H. pylori infection-negative patients following eradication showed associations with the degree of atrophy and intestinal metaplasia at both the anastomosis and in the corpus. Further, pH levels in these patients were normalized time depending after the eradication in the remnant stomach. Eradication therapy for the remnant stomach contributes to the possible improvement of stomach conditions by controlling the pH level of gastric juice. This effect will be protective against the risk of secondary stomach carcinogenesis in the remnant stomach.

The relationship between helicobacter pylori infection and gastro-esophageal reflux disease

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Batool M Mahdi

2011-01-01

Background : Gastro-esophageal reflux disease is a common condition, affecting 25%-40% of the population. Increasing attention has been paid to the relationship between Helicobacter pylori infection and reflux esophagitis. Aim: The aim of this study was to investigate the association between CagA+ H. pylori and endoscopically proven gastro-esophageal reflux disease. Patients and Methods: The study group included 60 hospital patients with gastro-esophageal reflux disease between 2007 and 2009 ...

When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children.

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Kienesberger, Sabine; Perez-Perez, Guillermo I; Olivares, Asalia Z; Bardhan, Pradip; Sarker, Shafiqul A; Hasan, Kh Zahid; Sack, R Bradley; Blaser, Martin J

2018-03-01

Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.

The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis

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Oleastro, Mónica; Ménard, Armelle

2013-01-01

Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1) colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2) evasion from the human immune system and (3) efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence. PMID:24833057

The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis

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Armelle Ménard

2013-08-01

Full Text Available Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1 colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2 evasion from the human immune system and (3 efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence.

Detection of Helicobacter pylori virulence factors and interleukin-1 polymorphisms in patients with abdominal complaint

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Anarkhuu, B.; Munguntsetseg, B.; Khosbayar, T.; Enkh-Amar, A.; Bayasgalan, P.; Yadamjav, Ch.; Oyuntsetseg, K.; Bira, N.; Choi, P.W.

2007-01-01

Full text: Gastric Cancer is the second leading cause of cancer related death in Mongolia (National Cancer Center, report-2006). Chronic infection with Helicobacter pylori affects approximately half the world and results in malignancy in a small subset of this population. There was sufficient evidence that the Working Group of the International Agency for Research on Cancer (IARC-1994) classified it as a class I carcinogen, the only bacterial agent on this list. The aim of the study is to detect and define the role of H.pylori virulence factors and host IL-1 polymorphisms to prevent further gastric cancer. In the future, this combined bacterial/host genotyping may provide an important opportunity to identify patients who are at high risk for the development of gastric carcinoma long before malignancy occurs. Patients and biopsy specimens. Two biopsy specimens and 5ml of blood samples were collected from each of 59 patients who had abdominal complaint, after informed consent was obtained. All patients lived in Ulaanbaatar, Mongolia, 100% were of Mongolian nationality. Their mean age was 40.33 years (range, 1575 years). One biopsy specimen was used to test urease, and another was stored for molecular testing. DNA isolation from blood and tissue sample was performed with ''Promega'' kit, according to the manufacturer's instruction. Tissue samples were homogenized treated with proteinase K prior to DNA extraction. H. pylori detection and genotyping. For H.pylori, detection was by UreC primer. For virulence gene typing of H.pylori cagA and vacA, gene specific primer were used. Genotyping of IL-1 polymorphisms. IL-1B polymorphisms were distinguished by 2 methods, 5-nuclease PCR assay and restriction fragment length polymorphism analysis (RFLP). Result. Strain characteristics of H. pylori were investigated in all 59 patients. 66,7% (40/59) and 76,3% (29/36) of the patients were infected with H. pylori by UreC PCR and by urea test, respectively. The vacAs1 genotype was

Frecuencia de genes de virulencia en infecciones mixtas con cepas de Helicobacter pylori de una población mexicana

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R. González-Vázquez

2016-01-01

Conclusiones: La prueba de Fisher no mostró una asociación significativa entre el resultado clínico y el genotipo en la población estudiada. Los genotipos circulantes en la población mexicana fueron cagA+, vacAs1, vacAm1. La PCR multiplex puede usarse para genotipificar rápidamente las cepas de H. pylori. cagE es un buen marcador para identificar cepas cag-PAI+.

Helicobacter pylori infection in women with Hashimoto thyroiditis: A case-control study.

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

2016-07-01

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 thyroid malfunction was independently associated with an increased risk of HT (odds ratio 3.39, 95% confidence interval 1.86-6.18, P thyroid malfunction is a risk factor for HT.

Foveolar cells phagocytose apoptotic neutrophils in chronic active Helicobacter pylori gastritis.

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Caruso, R A; Fedele, F; Di Bella, C; Mazzon, E; Rigoli, L

2012-11-01

The recognition and removal of apoptotic inflammatory cells by tissue macrophages and non-professional phagocytes, in a process called efferocytosis, is required for resolution of inflammation and is actively anti-inflammatory. We have previously demonstrated phagocytosis of apoptotic neutrophils by tumor cells in human gastric carcinoma, but to date, there have been no studies investigating this process in chronic active Helicobacter pylori gastritis. Biopsy specimens from 28 subjects with or without H. pylori infection and active inflammation were examined and graded according to the updated Sydney system. Light microscopy, electron microscopy, and Terminal Deoxynucleotidyltransferase-Mediated UTP End Labeling staining were used to identify apoptosis. H. pylori infection was detected by histology and by molecular assay in 16 out of 28 cases. DNA from paraffin-embedded gastric biopsies was amplified using primers specific for cagA, for the cag "empty site" as well as for the s and m alleles of vacA. The more virulent cagA-positive strains were found in five out of nine patients with chronic active gastritis. The vacA s1/m1 and s2/m1 genotypes were more common in nine patients with chronic active gastritis, while the vacA s2/m2 genotype was more frequent in seven patients with chronic inactive gastritis. Apoptotic neutrophils were also detected within the cytoplasmic vacuoles of the foveolar cells of nine cases with chronic active gastritis. Transmission electron micrographs revealed further apoptotic neutrophils within spacious phagosomes of foveolar cells in a similar manner to those described in late-phase efferocytosis both in vivo and in vitro. These new observations expand the morphological spectrum of gastritis in patients infected with more virulent H. pylori strains, compatible with an anti-inflammatory role for the gastric epithelial cells in their removal of apoptotic neutrophils during active chronic gastritis.

Correlation between virulence markers of Helicobacter pylori in the oral cavity and gastric biopsies

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Myriam Lucrecia MEDINA

2017-07-01

Full Text Available ABSTRACT BACKGROUND: The clinical outcome of Helicobacter pylori infection has been associated with virulence factors. The presence of these factors is useful as molecular markers in the identification of the high risk for developing severe gastric pathologies. OBJECTIVE: To correlate the presence of virulence markers cagA and bab2A of H. pylori in oral and gastric biopsy samples. METHODS: An observational, prospective, descriptive, and cross-sectional study was carried out between September 2011 and September 2012. Patients suffering dyspepsia with indication for upper gastrointestinal video endoscopy who attended the Gastroenterology Service of the Hospital Dr. Julio C. Perrando were included. Epidemiological investigation was completed. To detect the bacteria and their virulence genes, samples of saliva, dental plaque and gastric biopsy were taken and processed by PCR. RESULTS: Sixty-one patients were selected for this study (30 women and 31 men. H. pylori was detected in 31 gastric biopsies and 31 oral samples. Significant difference between oral and gastric samples was found in cagA genotype. Agreement between oral and gastric genotypes was found in 38.7% of samples from the same patient. CONCLUSION: This study is the first in provide information about the genotypes of the Argentinean Northeast H. pylori strains. Despite the high prevalence of H. pylori infection, the most of patients had less virulent genotypes in oral cavity and gastric tissue. The cagA / babA2 combination was not frequent in the samples studied. There was not a statistical correlation between the virulence genes and gastroduodenal or oral diseases. Although in some patients the same genotype was found both in oral and gastric samples, it cannot be ensure that they corresponding to the same strain because a DNA sequencing was not performed.

Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX-2 expression in patients with chronic gastritis and gastric cancer.

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Bartchewsky, Waldemar; Martini, Mariana Rocha; Masiero, Mariana; Squassoni, Aline Candido; Alvarez, Marisa Claudia; Ladeira, Marcelo Sady; Salvatore, Daisy; Trevisan, Miriam; Pedrazzoli, José; Ribeiro, Marcelo Lima

2009-01-01

Helicobacter pylori infection is related to gastric cancer development, and chronic inflammation is presumed to be the main cause. The aim of the present study was to evaluate the influence of H. pylori cagA, vacA, iceA, and babA genotypes on COX-2, IL-1beta, and IL-8 expression. Of the 217 patients included in the study, 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression values were determined by quantitative real-time PCR and immunohistochemistry. An association was found between the infection with cagA, vacA s1m1 strains and gastric cancer development. Regarding the 3' region of the cagA gene, we also found an association between the infection with cagA EPIYA-ABCCC strains and clinical outcome. Higher levels of IL-8, IL-1beta, and COX-2 were detected in gastric mucosa from infected patients with chronic gastritis, and they were also associated with the infection by cagA, vacA s1m1 strains. The IL-8 and IL-1beta levels decrease significantly from chronic gastritis to gastric cancer, while the relative expression remained unaltered when COX-2 expression was analyzed among patients with gastritis and cancer. Since inflammatory response to H. pylori infection plays an important role in cellular proliferation and gastric mucosal damage, the up-regulation of IL-1beta, IL-8, and COX-2 in patients with chronic gastritis has an important clinical implication in gastric carcinogenesis.

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

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Tran Thi Huyen Trang

2015-01-01

Full Text Available 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-(1,3galT(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-(1,3galT-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-(1,3galT-negative genotype may play a role in the development of gastric cancer.

Plasticity Region Genes jhp0940, jhp0945, jhp0947, and jhp0949 of Helicobacter pylori in Isolates from Mexican Children.

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Romo-González, Carolina; Consuelo-Sánchez, Alejandra; Camorlinga-Ponce, Margarita; Velázquez-Guadarrama, Norma; García-Zúñiga, Magdalena; Burgueño-Ferreira, Juan; Coria-Jiménez, Rafael

2015-06-01

The genes jhp0940, jhp0945, jhp0947, and jhp0949 belong to the plasticity region of the Helicobacter pylori genome. Due to their prevalence in isolates from patients with gastritis, duodenal ulcer, and gastric cancer, they have been proposed as markers of gastroduodenal diseases. These genes are associated with pro-inflammatory cytokine induction through the NF-κB activation pathway. Nevertheless, the status of these genes is unknown in H. pylori isolates from children. The aim of the present work was to determine the frequency of the jhp0940-jhp0945-jhp0947-jhp0949 genes in H. pylori isolates from children. We identified the jhp0940, jhp0945, jhp0947, and jhp0949 genes and the relationship of each with the virulence factors cagA, cagPAI, and dupA by PCR in 49 isolates of H. pylori from children. The results were corroborated using dot blots. In addition, we compared the prevalence of these genes with the prevalence in adults. The prevalence of jhp0940 (53.1%), jhp0945 (44.9%), jhp0947 (77.6%), and jhp0949 (83.7%) was determined in the isolates from children, as was the prevalence of the virulence genes cagA (63.3%), cagPAI (71.4%), and dupA (37.5%). No association was found between the four genes of the plasticity region and the virulence genes. The presence of the intact locus integrated by jhp0940-jhp0945-jhp0947-jhp0949 was very common among the isolates from children. The genes jhp0940, jhp0947, and jhp0949 were present in more than 50% of the H. pylori isolates, and the joint presence of jhp0940-jhp0945-jhp0947-jhp0949 was very frequent. The frequency of these genes in isolates from children could contribute to the virulence of H. pylori and the evolution of the infection. © 2015 John Wiley & Sons Ltd.

Helicobacter pylori HopE and HopV porins present scarce expression among clinical isolates

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Lienlaf, Maritza; Morales, Juan Pablo; Díaz, María Inés; Díaz, Rodrigo; Bruce, Elsa; Siegel, Freddy; León, Gloria; Harris, Paul R; Venegas, Alejandro

2010-01-01

AIM: To evaluate how widely Helicobacter pylori (H. pylori) HopE and HopV porins are expressed among Chilean isolates and how seroprevalent they are among infected patients in Chile. METHODS: H. pylori hopE and hopV genes derived from strain CHCTX-1 were cloned by polymerase chain reaction (PCR), sequenced and expressed in Escherichia coli AD494 (DE3). Gel-purified porins were used to prepare polyclonal antibodies. The presence of both genes was tested by PCR in a collection of H. pylori clinical isolates and their expression was detected in lysates by immunoblotting. Immune responses against HopE, HopV and other H. pylori antigens in sera from infected and non-infected patients were tested by Western blotting using these sera as first antibody on recombinant H. pylori antigens. RESULTS: PCR and Western blotting assays revealed that 60 and 82 out of 130 Chilean isolates carried hopE and hopV genes, respectively, but only 16 and 9, respectively, expressed these porins. IgG serum immunoreactivity evaluation of 69 H. pylori-infected patients revealed that HopE and HopV were infrequently recognized (8.7% and 10.1% respectively) compared to H. pylori VacA (68.1%) and CagA (59.5%) antigens. Similar values were detected for IgA serum immunoreactivity against HopE (11.6%) and HopV (10.5%) although lower values for VacA (42%) and CagA (17.4%) were obtained when compared to the IgG response. CONCLUSION: A scarce expression of HopE and HopV among Chilean isolates was found, in agreement with the infrequent seroconversion against these antigens when tested in infected Chilean patients. PMID:20082477

Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori

International Nuclear Information System (INIS)

Han Cong; Wang Qi; Dong Lei; Sun Haifang; Peng Shuying; Chen Jing; Yang Yiming; Yue Jianmin; Shen Xu; Jiang Hualiang

2004-01-01

Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K cat of 3.4 s -1 , K m of 1.7 mM, and K cat /K m of 2000 M -1 s -1 . HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 deg. C. The enzyme activity of Co 2+ -containing HpPDF is apparently higher than that of Zn 2+ -containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori

Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori.

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Han, Cong; Wang, Qi; Dong, Lei; Sun, Haifang; Peng, Shuying; Chen, Jing; Yang, Yiming; Yue, Jianmin; Shen, Xu; Jiang, Hualiang

2004-07-09

Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K(cat) of 3.4s(-1), K(m) of 1.7 mM, and K(cat) / K(m) of 2000M(-1)s(-1). HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 degrees C. The enzyme activity of Co(2+)-containing HpPDF is apparently higher than that of Zn(2+)-containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori.

The Prevalence of Helicobacter pylori in Estonian Bariatric Surgery Patients

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Natalja Šebunova

2018-01-01

Full Text Available Helicobacter pylori (Hp is one of the most important human pathogens that can cause duodenal and gastric ulcers, gastritis and stomach cancer. Hp infection is considered to be a cause of limiting access to bariatric surgery. The aim of this study was to determine the prevalence of Hp in patients with obesity going into bariatric surgery and to reveal the relationship between Hp and clinical data. The study group was formed of 68 preoperative bariatric surgery patients (body mass index (BMI 44.7 ± 4.8. Gastric biopsies (antrum and corpus were used for histological and molecular (caqA and glmM genes examinations. The PCR method revealed Hp infection in 64.7% of obese patients that is higher in comparison with histological analysis (55.9%. The prevalence of cagA and glmM genes in antrum mucosa was 45.6% and 47.0% while in the corpus it was 41.2% and 38.3%, respectively. The coincidence of both cagA and glmM virulence genes in the antrum and corpus mucosa was 33.8% and 22.1%, respectively. Either of the genes was found in 58.8% of antrum and 57.3% of corpus mucosa. Presence of caqA and glmM genes was in association with active and atrophic chronic gastritis. In conclusion, our study demonstrated that two thirds of morbidly obese patients undergoing bariatric surgery are infected with Hp and have a high prevalence of cagA and glmM virulence genes that points out the necessity for diagnostics and treatment of this infection before surgery.

Differences in Virulence Markers between Helicobacter pylori Strains from Iraq and Those from Iran: Potential Importance of Regional Differences in H. pylori-Associated Disease▿

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Hussein, Nawfal R.; Mohammadi, Marjan; Talebkhan, Yeganeh; Doraghi, Masoumeh; Letley, Darren P.; Muhammad, Merdan K.; Argent, Richard H.; Atherton, John C.

2008-01-01

Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma; the latter is common in Iran but not in Iraq. We hypothesized that more virulent H. pylori strains may be found in Iran than in Iraq and so compared established and newly described virulence factors in strains from these countries. We studied 59 unselected dyspeptic patients from Iran and 49 from Iraq. cagA was found in similar proportions of strains from both countries (76% in Iran versus 71% in Iraq) and was significantly associated with peptic ulcer disease in Iraq (P ≤ 0.01) but not in Iran. cagA alleles encoding four or more tyrosine phosphorylation motifs were found in 12% of the Iranian strains but none of the Iraqi strains (P = 0.02). There were no significant differences in the vacA signal-, middle-, or intermediate-region types between Iranian and Iraqi strains. Among the strains from Iran, vacA genotypes showed no specific peptic ulcer associations, but among the strains from Iraq, vacA i1 strains were associated with gastric ulcer (P ≤ 0.02), mimicking their previously demonstrated association with gastric cancer in Iran. dupA was found in similar proportions of Iranian and Iraqi strains (38% and 32%, respectively) and was associated with peptic ulceration in Iraqi patients (P ≤ 0.01) but not Iranian patients. H. pylori strains from Iraq and Iran possess virulence factors similar to those in Western countries. The presence of cagA with more phosphorylation motifs in Iranian strains may contribute to the higher incidence of gastric cancer. However, the association between strain virulence markers and disease in Iraq but not Iran suggests that other host and environmental factors may be more important in the disease-prone Iranian population. PMID:18353934

The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.

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Wang, You-Hua; Lv, Zhi-Fa; Zhong, Yao; Liu, Dong-Sheng; Chen, Shu-Ping; Xie, Yong

2017-02-01

Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. The internalization level in the eradication success group was 5.40±5.78 × 10 -3  cfu/cell, and the median was 6.194 × 10 -3  cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10 -3  cfu/cell, and the median was 10.28 × 10 -3  cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (Pinternalization levels were compared (P>.05). The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure. © 2016 John Wiley & Sons Ltd.

The Prevalence of Mixed Helicobacter pylori Infections in Symptomatic and Asymptomatic Subjects in Dhaka, Bangladesh.

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Kibria, Khandoker Mohammad K; Hossain, Md Enayet; Sultana, Jinath; Sarker, Shafiqul A; Bardhan, Pradip Kumar; Rahman, Motiur; Nahar, Shamsun

2015-10-01

Helicobacter pylori is a highly genetically diverse bacterial species, which can persist in the gastric environment for decades. Recent studies have shown that single infections predominate in developed countries, whereas mixed infections are more prevalent in developing countries. Mixed infections of this bacterium may be important for adaptation to the hostile gastric environment and may facilitate dyspeptic symptoms. To calculate the prevalence of mixed infections in symptomatic and asymptomatic subjects, 2010 H. pylori isolates collected from 83 symptomatic and 91 asymptomatic subjects from Dhaka, Bangladesh, were analyzed by (i) random amplified polymorphic DNA fingerprinting (RAPD) and (ii) multiplex PCR amplification for cagA and vacA virulence gene alleles. The overall prevalence of mixed H. pylori infection was 60.15% (77/128), indicating substantial co-colonization in this population. We additionally found that symptomatic subjects (53%) had a significantly higher rate of mixed infection than asymptomatic individuals (36.3%) (p = .016) and that the prevalence of the cagA and vacA and vacA m1/s1 and vacA m2/s1 alleles were higher in subjects with mixed infection. Our findings suggest that an increased diversity of the H. pylori strains in the gastric environment may contribute to the development of disease symptoms. © 2015 John Wiley & Sons Ltd.

CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study.

NARCIS (Netherlands)

Palli, D.; Masala, G.; Giudice, G. Del; Plebani, M.; Basso, D.; Berti, D.; Numans, M.E.; Ceroti, M.; Peeters, P.H.; Bueno de Mesquita, H.B.; Buchner, F.L.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Krogh, V.; Saieva, C.; Vineis, P.; Panico, S.; Tumino, R.; Nyren, O.; Siman, H.; Berglund, G.; Hallmans, G.; Sanchez, M.J.; Larrañaga, N.; Barricarte, A.; Navarro, C; Quiros, J.R.; Key, T.; Allen, N.; Bingham, S.; Khaw, K.T.; Boeing, H.; Weikert, C.; Linseisen, J.; Nagel, G.; Overvad, K.; Thomsen, R.W.; Tjonneland, A.; Olsen, A.; Trichoupoulou, A.; Trichopoulos, D.; Arvaniti, A.; Pera, G.; Kaaks, R.; Jenab, M.; Ferrari, P.; Nesi, G.; Carneiro, F.; Riboli, E.; Gonzalez, C.A.

2007-01-01

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries,

Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion

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Bodger, K; Bromelow, K; Wyatt, J; Heatley, R

2001-01-01

Background/Aims—Interleukin 10 (IL-10) is a counterinflammatory peptide implicated in the downregulation of human intestinal immune responses. Enhanced secretion of IL-10 has been documented in gastric biopsy organ culture in Helicobacter pylori infection. This study aimed to define the cellular origins of IL-10 in H pylori associated gastritis, and to determine the effects of endogenous IL-10 on proinflammatory cytokine secretion in vitro. Methods—Endoscopic biopsies were obtained from the gastric antrum at endoscopy from patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for 24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal antibody, the other pair as controls. The cytokine content of culture supernatants (tumour necrosis factor α (TNF-α), IL-6, and IL-8) was determined by enzyme linked immunosorbent assay and corrected for biopsy weight. Helicobacter pylori status was established by histology and biopsy urease test, and histopathology graded by the Sydney system. In a subgroup of patients, western blotting was used to establish CagA serological status. Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a combination of microwave antigen retrieval and the indirect avidin–biotin technique. Immunoreactivity was scored semiquantitatively. Results—In vitro culture was performed in 41 patients: 31 with H pylori positive chronic gastritis and 10 H pylori negative. In vitro secretion of TNF-α, IL-6, and IL-8 for "control" biopsies was significantly higher in H pylori positive versus negative samples, with values of TNF-α and IL-6 correlating with the degree of active and chronic inflammation and being higher in CagA seropositive cases. No evidence for enhanced cytokine secretion was seen in biopsies cocultured in the presence of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29 patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed in

Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells

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Machado, Ana Manuel Dantas; Figueiredo, Ceu; Touati, Eliette

2009-01-01

of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori infection, the activity and expression of base excision repair...... and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. CONCLUSIONS: Our results suggest that H. pylori...

Obacunone Represses Salmonella Pathogenicity Islands 1 and 2 in an envZ-Dependent Fashion

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Vikram, Amit; Jayaprakasha, Guddadarangavvanahally K.; Jesudhasan, Palmy R.

2012-01-01

Obacunone belongs to a class of unique triterpenoids called limonoids, present in Citrus species. Previous studies from our laboratory suggested that obacunone possesses antivirulence activity and demonstrates inhibition of cell-cell signaling in Vibrio harveyi and Escherichia coli O157:H7. The present work sought to determine the effect of obacunone on the food-borne pathogen Salmonella enterica serovar Typhimurium LT2 by using a cDNA microarray. Transcriptomic studies indicated that obacunone represses Salmonella pathogenicity island 1 (SPI1), the maltose transporter, and the hydrogenase operon. Furthermore, phenotypic data for the Caco-2 infection assay and maltose utilization were in agreement with microarray data suggesting repression of SPI1 and maltose transport. Further studies demonstrated that repression of SPI1 was plausibly mediated through hilA. Additionally, obacunone seems to repress SPI2 under SPI2-inducing conditions as well as in Caco-2 infection models. Furthermore, obacunone seems to repress hilA in an EnvZ-dependent fashion. Altogether, the results of the study seems to suggest that obacunone exerts an antivirulence effect on S. Typhimurium and may serve as a lead compound for development of antivirulence strategies for S. Typhimurium. PMID:22843534

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

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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

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

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Oleastro, Monica; Cordeiro, Rita; Yamaoka, Yoshio; Queiroz, Dulciene; Mégraud, Francis; Monteiro, Lurdes; Ménard, Armelle

2009-06-22

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

HELICOBACTER PYLORI

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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...

Identifying Pathogenicity Islands in Bacterial Pathogenomics Using Computational Approaches

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Dongsheng Che

2014-01-01

Full Text Available High-throughput sequencing technologies have made it possible to study bacteria through analyzing their genome sequences. For instance, comparative genome sequence analyses can reveal the phenomenon such as gene loss, gene gain, or gene exchange in a genome. By analyzing pathogenic bacterial genomes, we can discover that pathogenic genomic regions in many pathogenic bacteria are horizontally transferred from other bacteria, and these regions are also known as pathogenicity islands (PAIs. PAIs have some detectable properties, such as having different genomic signatures than the rest of the host genomes, and containing mobility genes so that they can be integrated into the host genome. In this review, we will discuss various pathogenicity island-associated features and current computational approaches for the identification of PAIs. Existing pathogenicity island databases and related computational resources will also be discussed, so that researchers may find it to be useful for the studies of bacterial evolution and pathogenicity mechanisms.

Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection.

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Bagheri, Nader; Shirzad, Hedayatollah; Elahi, Shokrollah; Azadegan-Dehkordi, Fatemeh; Rahimian, Ghorbanali; Shafigh, Mohammedhadi; Rashidii, Reza; Sarafnejad, Abdulfatah; Rafieian-Kopaei, Mahmoud; Faridani, Rana; Tahmasbi, Kamran; Kheiri, Soleiman; Razavi, Alireza

2017-09-01

Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-β1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). The numbers of CD4 + and Foxp3 + T cells as well as the expression of IL-10, TGF-β1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4 + T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3 + T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3 + T cells and the expression of IL-10, TGF-β1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4 + T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4 + and Foxp3 + T cells as well as the expression of IL-10, TGF-β1, FOXP3 and INF-γ were positively

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

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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.

Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells

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Rieder Gabriele

2011-11-01

Full Text Available Abstract Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS and the effector protein cytotoxin-associated gene A (CagA of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells.

Phylogeographic origin of Helicobacter pylori determines host-adaptive responses upon coculture with gastric epithelial cells.

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Sheh, Alexander; Chaturvedi, Rupesh; Merrell, D Scott; Correa, Pelayo; Wilson, Keith T; Fox, James G

2013-07-01

While Helicobacter pylori infects over 50% of the world's population, the mechanisms involved in the development of gastric disease are not fully understood. Bacterial, host, and environmental factors play a role in disease outcome. To investigate the role of bacterial factors in H. pylori pathogenesis, global gene expression of six H. pylori isolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factors cagA, vacA, and babB and were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis. Our data suggest that gene expression profiles of clinical isolates can discriminate strains by phylogeographic origin and that these profiles are associated with changes in expression of the proinflammatory and protumorigenic cytokine IL-8 and levels of apoptosis in host epithelial cells. These findings support the hypothesis that bacterial factors determined by the phylogeographic origin of H. pylori strains may promote increased gastric disease.

Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

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Oktem-Okullu, Sinem; Tiftikci, Arzu; Saruc, Murat; Cicek, Bahattin; Vardareli, Eser; Tozun, Nurdan; Kocagoz, Tanil; Sezerman, Ugur; Yavuz, Ahmet Sinan; Sayi-Yazgan, Ayca

2015-01-01

The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

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.

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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 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. © 2016 UICC.

Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

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Sinem Oktem-Okullu

Full Text Available The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1, IL-17 (Th17, and FOXP3 (Treg expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

Electron Microscopic, Genetic and Protein Expression Analyses of Helicobacter acinonychis Strains from a Bengal Tiger

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Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred; Oyarzabal, Omar A.; Lehn, Norbert; Schneider-Brachert, Wulf; Ferrero, Richard L.; Fox, James G.; Berg, Douglas E.; Backert, Steffen

2013-01-01

Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy) and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms) as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5–6 µm) and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers) from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections. PMID:23940723

Electron microscopic, genetic and protein expression analyses of Helicobacter acinonychis strains from a Bengal tiger.

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Nicole Tegtmeyer

Full Text Available Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5-6 µm and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections.

Electron microscopic, genetic and protein expression analyses of Helicobacter acinonychis strains from a Bengal tiger.

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Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred; Oyarzabal, Omar A; Lehn, Norbert; Schneider-Brachert, Wulf; Ferrero, Richard L; Fox, James G; Berg, Douglas E; Backert, Steffen

2013-01-01

Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy) and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms) as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5-6 µm) and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers) from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections.

Helicobacter pylori virulence genes and microevolution in host and the clinical outcome: review article

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Seyedeh Zahra Bakhti

2014-12-01

Full Text Available Helicobacter pylori (H. pylori is the causative agent in development of gastroduode-nal diseases, such as chronic atrophic gastritis, peptic ulcers, mucosa associated lym-phoid tissue (MALT lymphoma, and gastric cancer. H. pylori has been associated with inflammation in cardia, showing the fact that infection with this bacterium could also be a risk factor for gastric cardia cancer. Gastric cancer is the fourth most common cancer worldwide. This is the second leading cause of cancer-related deaths, and ap-proximately 700,000 people succumb each year to gastric adenocarcinoma. It has been estimated that 69% of the Iranian population currently harbor H. pylori infection. The prevalence of duodenal ulcer and gastric cancer is high in Iranian populations. However, this has been largely influenced by geographic and/or ethnic origin. Epidemi-ology studies have shown that host, environmental, and bacterial factors determine the outcome of H. pylori infection. The bacterium contains allelic diversity and high genet-ic variability into core- and virulence-genes and that this diversity is geographically and ethnically structured. The genetic diversity within H. pylori is greater than within most other bacteria, and its diversity is more than 50-fold higher than that of human DNA. The maintenance of high diversification makes this bacterium to cope with particular challenges in individual hosts. It has been reported that the recombination contributed to the creation of new genes and gene family. Furthermore, the microevolution in cagA and vacA genes is a common event, leading to a change in the virulence phenotype. These factors contribute to the bacterial survival in acidic conditions in stomach and protect it from host immune system, causing tissue damage and clinical disease. In this review article, we discussed the correlation between H. pylori virulence factors and clin-ical outcomes, microevolution of H. pylori virulence genes in a single host

Helicobacter pylori colonization critically depends on postprandial gastric conditions

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Bücker, Roland; Azevedo-Vethacke, Marina; Groll, Claudia; Garten, Désirée; Josenhans, Christine; Suerbaum, Sebastian; Schreiber, Sören

2012-01-01

The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood. PMID:23251780

The Helicobacter pylori duodenal ulcer promoting gene, dupA in China

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Liu Wenzhong

2008-10-01

Full Text Available Abstract Background The prevalence of H. pylori is as high as 60–70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors. Methods H. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU, gastric ulcer (GU, or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1β polymorphism was investigated using restriction fragment length polymorphism. Results Isolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360 and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058. The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1β polymorphisms. Conclusion In China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer.

The Helicobacter pylori duodenal ulcer promoting gene, dupA in China.

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Zhang, Zhiyu; Zheng, Qing; Chen, Xiaoyu; Xiao, Shudong; Liu, Wenzhong; Lu, Hong

2008-10-25

The prevalence of H. pylori is as high as 60-70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA) gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors. H. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU), gastric ulcer (GU), or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1beta polymorphism was investigated using restriction fragment length polymorphism. Isolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360) and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058). The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1beta polymorphisms. In China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer.

Biofilm formation enhances Helicobacter pylori survivability in vegetables.

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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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neither genotype nor the gastric colonization site of Helicobacter pylori are predictive factors for the development of erosive esophagitis in patients with peptic ulcer disease, 1 year after eradication O genótipo e o local no estômago de isolamento do Helicobacter pylori em pacientes com úlcera péptica não são fatores preditivos para o desenvolvimento de esofagite erosiva 1 ano após a erradicação da bactéria

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Carlos Alexandre Gonçalves Batista

2009-09-01

Full Text Available CONTEXT: Whether Helicobacter pylori infection is a protective or predisposing factor for the development of gastroesophageal reflux disease remains controversial. The most virulent strains, such as those expressing the cytotoxin-associated gene A (CagA, and the site of gastric colonization have been correlated with the prevention or development of esophagitis. AIM: To determine the incidence of erosive esophagitis following eradication of H. pylori in patients with peptic ulcer disease and to evaluate the association of erosive esophagitis with virulent strains of H. pylori and the site of gastric colonization. METHODS: Triple therapy with lansoprazole, amoxicillin and clarithromycin was administered to 159 patients with peptic ulcer disease. Endoscopy, histopathology, urease and carbon-14 urea breath tests were performed prior to treatment, at 3 months and 1 year following treatment. Genotyping of H. pylori strains using polymerase chain reaction was performed separately on samples from the corpus and antrum. RESULTS: One year after treatment, 148 successfully treated patients were reevaluated. Twenty-eight patients (19% had erosive esophagitis, classified as Los Angeles grade A in 24 and B in 4. The samples taken from the corpus were CagA-positive in 18 patients (64%, while the samples taken from the antrum were CagA-positive in 21 patients (75%. CONCLUSIONS: The incidence of erosive esophagitis in peptic ulcer patients who had their H. pylori eradicated was 19%. No correlation was found between the gastric site colonized by H. pylori or strains expressing CagA and the prevention or development of erosive esophagitis in patients with peptic ulcer disease, 1 year after infection eradication.CONTEXTO: É controverso se a infecção pelo Helicobacter pylori é um fator de proteção ou de predisposição para o desenvolvimento da doença de refluxo gastroesofágico. Cepas mais virulentas tais como as que expressam a citotoxina CagA e o local no

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

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

2016-10-11

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 periodontitis-related molecules Wnt5a, interleukin 8 (IL-8), interleukin 6 (IL-6) and interferon gamma (IFN-γ) significantly increased (p periodontal pathogens and aggravate the progress of chronic periodontitis.

Persistent colonization of Helicobacter pylori in human gut induces gastroduodenal diseases

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Animesh Sarker

2014-12-01

Full Text Available Helicobacter pylori are gut bacteria colonize in the epithelial cell lining of the stomach and persist there for long du­ration. Around two-thirds of the world’s populations are infected with H. pylori and cause more than 90 percent of ulcers. The development of persistent inflammation is the main cause of chronic gastritis that finally results in a severe consequence known as stomach cancer. Two major virulence factors cytotoxin-associated gene product (cagA and the vacuolating toxin (vacA are mostly investigated as their close association with gastric carcinoma. In this review, host im­munity against H. pylori infection and their evasion mechanism are intensely explored. It is the fact, that understanding pin point molecular mechanisms of any infection is critical to develop novel strategies to prevent pertinent diseases. .J Microbiol Infect Dis 2014; 4(4: 170-176

Could gastric histology be a useful marker for making decision on Helicobacter pylori eradication therapy in patients with dyspepsia? É a histologia gástrica um marcador útil na decisão de erradicar o Helicobacter pylori nos pacientes com dispepsia?

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Severino Marcos Borba de Arruda

2009-09-01

Full Text Available CONTEXT: It still remains an open debate whether Helicobacter pylori eradication is beneficial or not for the improvement of symptoms in functional dyspepsia. Differences in geographic distribution, the worldwide H. pylori genetic variability and the fact that the outcome of infection is strongly related to the virulence of the infecting strain are factors that might be driving ongoing controversies. OBJECTIVE: To study the correlation between gastric histology and H. pylori serology status in patients with dyspepsia. METHODS: This is a cross-sectional study where 40 consecutive dyspeptic patients (28 women and 12 men, mean age 48.5 years with endoscopically normal stomachs were selected from the endoscopy unit at a university hospital in Recife, PE, Northeast of Brazil, between March 1998 and July 1999. Patients underwent gastric mucosal biopsy and serological tests (anti-Hp and anti-CagA antibodies. Gastric biopsies were examined using H-E and Giemsa stains and gastritis was classified and graded (mild, moderate or severe according to "the updated Sydney System - Houston, 1994". RESULTS: Among 40 patients with dyspepsia the gastric histology revealed that about ¼ had moderate (25% or severe (2.5% gastritis. This subgroup of patients also had a greater positive frequency of anti-Hp (100% vs 41%; P = 0.0005 and anti-CagA (91% vs 58%; P = 0.09 antibodies when compared with those with normal histology (27.5% or mild gastritis (45%. CONCLUSION: Since upper gastrointestinal endoscopy is part of the functional dyspepsia investigation and serology for anti-CagA antibody is not available in daily clinical practice, by biopsying gastric mucosa we would only be able to selectively apply H. pylori eradication therapy for those with histology that best correlate with virulent infecting strains (moderate or severe gastritis - around ¼ of our study patients with dyspepsia.CONTEXTO: O benefício da terapia de erradicação do H. pylori como parte do

adolescents with gastroduodenal disease

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Monika Maria Biernat

2014-08-01

Full Text Available Introduction: Infection with Helicobacter pylori is a major cause of chronic gastritis and peptic ulcer disease in children and its consequences in adulthood can lead to serious complications, including in particular the development of gastric cancer. Our aim was to analyze the relationship between the occurrence of selected genes such as cagA, vacA, iceA, and babA2 determining pathogenicity of H. pylori strains and clinical outcome in children.Material and methods: The study was performed on H. pylori strains isolated from biopsies taken from 130 children and adolescents with non-ulcer dyspepsia (NUD, gastric and duodenal ulcers (PUD and gastroesophageal reflux disease (GERD. Genes such as cagA, vacA (allelic variants: s1/ s2, m1/m2, iceA (allelic variants: iceA1, iceA2 and babA2 were determined by polymerase chain reaction (PCR.Results: The cagA gene was detected in 79/130 (60.8% H. pylori isolates. The presence of the cagA gene was significantly associated with duodenal ulcer (p<0.05. The vacAs1/m1 genotype as more frequent in children with ulcers than in other groups, whereas the vacAs2/m2 genotype was more frequent in patients with gastritis and GERD. The iceA1, iceA2 and babA2 genes were present in 59/130 (45.4%, 27/130 (21% and 30/130 (23.1% of the strains, respectively. The vacAs1/cagA+ genotype was most frequently observed in strains isolated from children with PUD. The predominant genotype in children with NUD and GERD was vacAs2/cagA-/iceA1+/babA2-.Conclusion: The study showed a high incidence of strains with increased virulence, possessing cagA, vacAs1 and iceA1 genes in symptomatic children with H. pylori infection.

Relationship between ureB Sequence Diversity, Urease Activity and Genotypic Variations of Different Helicobacter pylori Strains in Patients with Gastric Disorders.

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Ghalehnoei, Hossein; Ahmadzadeh, Alireza; Farzi, Nastaran; Alebouyeh, Masoud; Aghdaei, Hamid Asadzadeh; Azimzadeh, Pendram; Molaei, Mahsa; Zali, Mohammad Reza

2016-01-01

Association of the severity of Helicobacter pylori induced diseases with virulence entity of the colonized strains was proven in some studies. Urease has been demonstrated as a potent virulence factor for H. pylori. The main aim of this study was investigation of the relationships of ureB sequence diversity, urease activity and virulence genotypes of different H. pylori strains with histopathological changes of gastric tissue in infected patients suffering from different gastric disorders. Analysis of the virulence genotypes in the isolated strains indicated significant associations between the presence of severe active gastritis and cagA+ (P = 0.039) or cagA/iceA1 genotypes (P = 0.026), and intestinal metaplasia and vacA m1 (P = 0.008) or vacA s1/m2 (P = 0.001) genotypes. Our results showed a 2.4-fold increased risk of peptic ulcer (95% CI: 0.483-11.93), compared with gastritis, in the infected patients who had dupA positive strains; however this association was not statistically significant. The results of urease activity showed a significant mean difference between the isolated strains from patients with PUD and NUD (P = 0.034). This activity was relatively higher among patients with intestinal metaplasia. Also a significant association was found between the lack of cagA and increased urease activity among the isolated strains (P = 0.036). While the greatest sequence variation of ureB was detected in a strain from a patient with intestinal metaplasia, the sole determined amino acid change in UreB sequence (Ala201Thr, 30%), showed no influence on urease activity. In conclusion, the supposed role of H. pylori urease to form peptic ulcer and advancing of intestinal metaplasia was postulated in this study. Higher urease activity in the colonizing H. pylori strains that present specific virulence factors was indicated as a risk factor for promotion of histopathological changes of gastric tissue that advance gastric malignancy.

Genetic fine structure analysis of helicobacter pylori isolates before and after treatment

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Rekha T

2003-01-01

Full Text Available BACKGROUND: Eradication of H. pylori infection cures peptic ulcer disease and conversely, relapse is associated with reappearance of H. pylori infection. However, it is not clear whether the recurrence of ulcers following H. pylori eradication is due to recrudescence (identical strain of the previous infection or as a result of exogenous reinfection (different strain by another strain. The aim of the present study was to analyze the FAFLP patterns of pre and post treatment H. pylori samples to check if the recurrence was due to recrudescence or reinfection. MATERIALS AND METHODS: 24 of 30 duodenal ulcer (DU subjects screened for H. pylori infection were positive for H. pylori infection. The treatment regime included pantoprazole, ciprofloxacin and amoxicillin. The patients were called for a repeat endoscopy after one month and screened for H. pylori infection. FAFLP analysis and PCR for the cagA and vacA gene was performed for the pre and post treatment samples. RESULTS: Of the 24 positive H.pylori patients, only 6 were negative after treatment and the remaining 18 were positive for H.pylori infection. The analysis of the pre and post treatment samples of the 18 patients showed that the FAFLP profiles of the initial and follow-up pools were similar to one another. CONCLUSION: It can be concluded that in the present series of patients, reinfection was due to recrudescence of infection due to incomplete eradication. The study also suggests that DNA fingerprinting by FAFLP provides discriminatory and complementary data for identifying strains of H. pylori while monitoring therapy.

Using macro-arrays to study routes of infection of Helicobacter pylori in three families.

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Josette Raymond

Full Text Available BACKGROUND: Analysis of the evolutionary dynamics of Helicobacter pylori allowed tracing the spread of infection through populations on different continents but transmission pathways between individual humans have not been clearly described. MATERIALS AND METHODS: To investigate person-to-person transmission, we studied three families each including one child with persistence of symptoms after antibiotic treatment. Ten isolates from the antrum and corpus of stomach of each family member were analyzed both by sequencing of two housekeeping genes and macroarray tests. RESULTS: A total of 134 (8.4% out of the 1590 coding sequences (CDSs tested, including cag PAI and insertion sequences, were present in some but not all isolates (and are therefore defined as variable CDSs. Most of the variable CDSs encoded proteins of unknown function (76/134 or were selfish DNA including that encoding restriction/modification enzymes (13/134. Isolates colonizing the stomach of one individual can vary by point mutations, as seen in hspA, or by the gain or loss of one to five CDSs. They were considered as (genetic variants. The phylogenetic clustering of gene profiles obtained on macro-arrays allowed identifying the different strains infecting families. Two to five strains circulated within a family. Identical strains were present in at least two members of all three families supporting the accepted model of intrafamilial transmission. Surprisingly, the mother was not implicated in the transmission of H. pylori in the two French families. Sibling-to-sibling transmission and acquisition of H. pylori from outside the family appeared to be probable in the transmission pathways. CONCLUSION: Macroarray analysis based on previously selected CDSs gives a comprehensive view of the genome diversity of a pathogen. This approach combined with information on the origin of the hspA and glmM alleles revealed that Helicobacter pylori infection may be acquired by more diverse routes

Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension

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Lee Na

2011-05-01

Full Text Available Abstract Background Helicobacter pylori (Hp, a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O2 requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s of Hp infection. Results We cultured Hp under a range of O2 levels with or without 10% CO2 and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO2, the normal atmospheric level of O2 inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O2 tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO2 deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response. Conclusions We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of H. pylori and that CO2 deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.

MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

Science.gov (United States)

Dumitrescu, Laura; Popescu, Bogdan O

2015-01-01

MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

Is there a link between the lipopolysaccharide of Helicobacter pylori gastric MALT lymphoma associated strains and lymphoma pathogenesis?

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Philippe Lehours

Full Text Available The aim of this study was to investigate the Lewis antigen expression in Helicobacter pylori gastric MALT lymphoma associated strains in comparison to chronic gastritis only strains. Forty MALT strains (19 cagPAI (- and 21 cagPAI (+ and 39 cagPAI frequency-matched gastritis strains (17 cagPAI (- and 22 cagPAI (+ were included in this study. The lipopolyssacharide for each strain was extracted using a hot phenol method and the expression of Le(x and Le(y were investigated using Western Blot. The data were analyzed according to the strains' cagPAI status and vacA genotype. Le(x was identified in 21 (52.5% MALT strains and 29 (74.3% gastritis strains. Le(y was identified in 30 (75% MALT strains and 31 (79.5% gastritis strains. There was an association between cagPAI positivity and Le(x expression among MALT strains (p<0.0001, but not in gastritis strains (p = 0.64. Among cagPAI (- strains, isolates expressing solely Le(y were associated with MALT with an odds ratio of 64.2 (95% CI 4.9-841.0 when compared to strains expressing both Le(x and Le(y. vacA genotypes did not modify the association between Lewis antigen expression and disease status. In conclusion, cagPAI (- MALT strains have a particular Lewis antigen profile which could represent an adaptive mechanism to the host response or participate in MALT lymphomagenesis.

Rolle verschiedener sekretierter oder translokalisierter Effektormoleküle des gastrischen Pahogens Helicobacter pylori

OpenAIRE

Lind, Judith

2015-01-01

H. pylori is estimated to colonize the human stomach in almost 50% of the world population and has established itself as survival specialist by avoiding host cell recognition and elimination. Pathologic effects due to its persistence are depending on a multitude of host-pathogen interactions and infection may develop from simple symptoms to chronic gastritis, peptic ulcer or even cancer formation. More virulent strains of H. pylori encode a type IV secretion system (T4SS) able to translocate ...

Detection of Helicobacter pylori vacA, cagA and iceA1 virulence ...

African Journals Online (AJOL)

Ahmed El-Shenawy

related genes in different age group patients with ... vacA and iceA1 genotypes of H. pylori strains recovered from patients with dyspepsia. Subjects and methods: ..... many decades in the absence of antimicrobial treatment. Longitu- dinal studies ...

CRISPR-Cas and Contact-Dependent Secretion Systems Present on Excisable Pathogenicity Islands with Conserved Recombination Modules.

Science.gov (United States)

Carpenter, Megan R; Kalburge, Sai S; Borowski, Joseph D; Peters, Molly C; Colwell, Rita R; Boyd, E Fidelma

2017-05-15

Pathogenicity islands (PAIs) are mobile integrated genetic elements that contain a diverse range of virulence factors. PAIs integrate into the host chromosome at a tRNA locus that contains their specific bacterial attachment site, attB , via integrase-mediated site-specific recombination generating attL and attR sites. We identified conserved recombination modules (integrases and att sites) previously described in choleragenic Vibrio cholerae PAIs but with novel cargo genes. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated proteins (Cas proteins) and a type VI secretion system (T6SS) gene cluster were identified at the Vibrio pathogenicity island 1 (VPI-1) insertion site in 19 V. cholerae strains and contained the same recombination module. Two divergent type I-F CRISPR-Cas systems were identified, which differed in Cas protein homology and content. The CRISPR repeat sequence was identical among all V. cholerae strains, but the CRISPR spacer sequences and the number of spacers varied. In silico analysis suggests that the CRISPR-Cas systems were active against phages and plasmids. A type III secretion system (T3SS) was present in 12 V. cholerae strains on a 68-kb island inserted at the same tRNA-serine insertion site as VPI-2 and contained the same recombination module. Bioinformatics analysis showed that two divergent T3SSs exist among the strains examined. Both the CRISPR and T3SS islands excised site specifically from the bacterial chromosome as complete units, and the cognate integrases were essential for this excision. These data demonstrated that identical recombination modules that catalyze integration and excision from the chromosome can acquire diverse cargo genes, signifying a novel method of acquisition for both CRISPR-Cas systems and T3SSs. IMPORTANCE This work demonstrated the presence of CRISPR-Cas systems and T3SSs on PAIs. Our work showed that similar recombination modules can associate with different cargo genes and

Helicobacter pylori genotypes and types of gastritis in first-degree relatives of gastric cancer patients.

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Siavoshi, F; Asgharzadeh, A; Ghadiri, H; Massarrat, S; Latifi-Navid, S; Zamani, M

2011-08-01

The frequency of Helicobacter pylori vacA alleles, cagA, and jhp0947 and their association with types and advanced forms of gastritis in 143 first-degree relatives of gastric cancer (GC) patients was assessed. The subjects included 64/143 with antral-predominant gastritis, 68/143 with pangastritis, and 11/143 with corpus-predominant gastritis, with or without atrophy or intestinal metaplasia (IM). Further classification included the severity of atrophy or IM. Group I (40/143) included the subjects with moderate-marked atrophy or IM, group II (58/143) those with no atrophy or IM, and group III (45/143) with mild atrophy or IM. The frequency of vacA s1 was 79.7%, vacA s2 20.3%, m1 49.7%, m2 50.3%, cagA 76.2%, and jhp0947 58%. The most prevalent combination was vacAs1 cagA (+) (65.7%) (P=0.001). Of the 143 subjects, 85 (59.4%) showed atrophy or IM, and 40/85 (47%) developed the moderate-marked atrophy or IM. No significant correlation was found between genotypes and the types of gastritis, non-atrophy, atrophy, or IM and severe forms of atrophy or IM (P>0.05). It is proposed that H. pylori genotype status might not be considered as an important determinant of the types and advanced forms of gastritis in the first-degree relatives of GC patients. Copyright © 2011 Elsevier GmbH. All rights reserved.

Helicobacter pylori genetic diversification in the Mongolian gerbil model.

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Beckett, Amber C; Loh, John T; Chopra, Abha; Leary, Shay; Lin, Aung Soe; McDonnell, Wyatt J; Dixon, Beverly R E A; Noto, Jennifer M; Israel, Dawn A; Peek, Richard M; Mallal, Simon; Algood, Holly M Scott; Cover, Timothy L

2018-01-01

Helicobacter pylori requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed H. pylori genetic adaptation in the Mongolian gerbil model. This model is of particular interest because H. pylori -infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration. We analyzed the whole genome sequences of H. pylori strains cultured from experimentally infected gerbils, in comparison to the genome sequence of the input strain. The mean annualized single nucleotide polymorphism (SNP) rate per site was 1.5e -5 , which is similar to the rates detected previously in H. pylori- infected humans. Many of the mutations occurred within or upstream of genes associated with iron-related functions ( fur , tonB1 , fecA2 , fecA3 , and frpB3 ) or encoding outer membrane proteins ( alpA, oipA, fecA2, fecA3, frpB3 and cagY ). Most of the SNPs within coding regions (86%) were non-synonymous mutations. Several deletion or insertion mutations led to disruption of open reading frames, suggesting that the corresponding gene products are not required or are deleterious during chronic H. pylori colonization of the gerbil stomach. Five variants (three SNPs and two deletions) were detected in isolates from multiple animals, which suggests that these mutations conferred a selective advantage. One of the mutations (FurR88H) detected in isolates from multiple animals was previously shown to confer increased resistance to oxidative stress, and we now show that this SNP also confers a survival advantage when H. pylori is co-cultured with neutrophils. Collectively, these analyses allow the identification of mutations that are positively selected during H. pylori colonization of the gerbil model.

Helicobacter pylori impairs murine dendritic cell responses to infection.

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Ya-Hui Wang

Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

N-acetylcysteine prevents the development of gastritis induced by Helicobacter pylori infection.

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Jang, Sungil; Bak, Eun-Jung; Cha, Jeong-Heon

2017-05-01

Helicobacter pylori (H. pylori) is a human gastric pathogen, causing various gastric diseases ranging from gastritis to gastric adenocarcinoma. It has been reported that combining N-acetylcysteine (NAC) with conventional antibiotic therapy increases the success rate of H. pylori eradication. We evaluated the effect of NAC itself on the growth and colonization of H. pylori, and development of gastritis, using in vitro liquid culture system and in vivo animal models. H. pylori growth was evaluated in broth culture containing NAC. The H. pylori load and histopathological scores of stomachs were measured in Mongolian gerbils infected with H. pylori strain 7.13, and fed with NAC-containing diet. In liquid culture, NAC inhibited H. pylori growth in a concentration-dependent manner. In the animal model, 3-day administration of NAC after 1 week from infection reduced the H. pylori load; 6-week administration of NAC after 1 week from infection prevented the development of gastritis and reduced H. pylori colonization. However, no reduction in the bacterial load or degree of gastritis was observed with a 6-week administration of NAC following 6-week infection period. Our results indicate that NAC may exert a beneficial effect on reduction of bacterial colonization, and prevents the development of severe inflammation, in people with initial asymptomatic or mild H. pylori infection.

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

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Polakovicova, Iva; Jerez, Sofia; Wichmann, Ignacio A.; Sandoval-Bórquez, Alejandra; Carrasco-Véliz, Nicolás; Corvalán, Alejandro H.

2018-01-01

Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs), influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1) which are delivered into

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

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Iva Polakovicova

2018-04-01

Full Text Available Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori, a bacterium present in half of the world population; or by Epstein-Barr virus (EBV, a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs, influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA, a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1 which are

Motion – Helicobacter pylori Causes or Worsens GERD: Arguments against the Motion

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Kenneth EL McColl

2002-01-01

Full Text Available Data from large epidemiological studies show that Helicobacter pylori is less prevalent in patients with gastroesophageal reflux disease (GERD than in control subjects. The more virulent cagA-positive strains of the organism are also less commonly seen in patients with erosive esophagitis and in those with Barrett's esophagus than in those with less severe forms of GERD. Although the relationship between H pylori and gastric physiology is complex, the organism has little effect on acid secretion in most North American or Western European subjects, and has a net suppressive effect, especially in elderly subjects, in other parts of the world. Thus, the organism has a potential protective effect against GERD, which is exacerbated by gastric acidity. H pylori has no proven effect on other gastric factors that might provoke reflux, including delayed gastric emptying or inappropriate relaxation of the gastric fundus. Two well-designed interventional studies have found that eradication of H pylori either provoked GERD or had no effect. A third smaller study, which seemed to demonstrate that persistent infection was associated with GERD, was flawed, in that the two treatment groups were not comparable. The evidence thus does not support the idea that H pylori infection provokes or aggravates GERD.

Cell-cycle inhibition by Helicobacter pylori L-asparaginase.

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Claudia Scotti

Full Text Available Helicobacter pylori (H. pylori is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application.

Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen

LENUS (Irish Health Repository)

O'Toole, Paul W

2010-03-10

Abstract Background Helicobacter mustelae causes gastritis, ulcers and gastric cancer in ferrets and other mustelids. H. mustelae remains the only helicobacter other than H. pylori that causes gastric ulceration and cancer in its natural host. To improve understanding of H. mustelae pathogenesis, and the ulcerogenic and carcinogenic potential of helicobacters in general, we sequenced the H. mustelae genome, and identified 425 expressed proteins in the envelope and cytosolic proteome. Results The H. mustelae genome lacks orthologs of major H. pylori virulence factors including CagA, VacA, BabA, SabA and OipA. However, it encodes ten autotransporter surface proteins, seven of which were detected in the expressed proteome, and which, except for the Hsr protein, are of unknown function. There are 26 putative outer membrane proteins in H. mustelae, some of which are most similar to the Hof proteins of H. pylori. Although homologs of putative virulence determinants of H. pylori (NapA, plasminogen adhesin, collagenase) and Campylobacter jejuni (CiaB, Peb4a) are present in the H. mustelae genome, it also includes a distinct complement of virulence-related genes including a haemagglutinin\\/haemolysin protein, and a glycosyl transferase for producing blood group A\\/B on its lipopolysaccharide. The most highly expressed 264 proteins in the cytosolic proteome included many corresponding proteins from H. pylori, but the rank profile in H. mustelae was distinctive. Of 27 genes shown to be essential for H. pylori colonization of the gerbil, all but three had orthologs in H. mustelae, identifying a shared set of core proteins for gastric persistence. Conclusions The determination of the genome sequence and expressed proteome of the ulcerogenic species H mustelae provides a comparative model for H. pylori to investigate bacterial gastric carcinogenesis in mammals, and to suggest ways whereby cag minus H. pylori strains might cause ulceration and cancer. The genome sequence was

VacA, CagA, IceA and OipA Genotype Status of Helicobacter pylori ...

African Journals Online (AJOL)

particularly can ease loneliness, reduce allergies, anxiety, depression, stress, and a variety of human diseases, and .... isolated from food stuff was also statistically analyzed. ..... Helicobacter pylori strains from the high-altitude desert of Ladakh ...

The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease

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Dan-dan Cheng

2017-05-01

Full Text Available Helicobacter pylori (H. pylori which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD. Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.

Adherence of Helicobacter pylori to the Gastric Mucosa

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Marguerite Clyne

1997-01-01

Full Text Available Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.

Searching for Helicobacter pylori and Chlamydia pneumoniae in primary endodontic infections.

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Rôças, Isabela N; Siqueira, José F

2012-04-01

The purpose of this study was to search samples from primary endodontic infections for the presence of two common human bacterial pathogens - Helicobacter pylori and Chlamydia pneumoniae. Genomic DNA isolated from samples taken from 25 root canals of teeth with asymptomatic (chronic) apical periodontitis and 25 aspirates from acute apical abscess was initially amplified by the multiple displacement amplification approach and then used as template in species-specific polymerase chain reaction (PCR) for detection of H. pylori and C. pneumoniae. All clinical samples were positive for the presence of bacterial DNA. However, no clinical sample was positive for either H. pylori or C. pneumoniae. Neither H. pylori nor C. pneumoniae were found in samples from primary endodontic infections. These findings suggest that these species are not candidate endodontic pathogens and that the necrotic root canal does not serve as a reservoir for these human pathogens in healthy patients.

Association between interleukin-1 β polymorphisms and gastric disease in children: A correlation with Helicobacter pylori

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Luanna Munhoz Zabaglia

2016-09-01

Full Text Available Objective: To investigate an association between the interleukin-1β (IL-1β -511 T>C (rs16944, -31 C>T (rs1143627, and/or interleukin-1 receptor antagonist (IL-1RA polymorphisms and gastritis and then to correlate any associations with the presence of Helicobacter pylori (H. pylori, cagA and vacA genes. Methods: Gastric biopsies were obtained from 377 children with gastric symptoms including 152 males and 225 females aging from 1–15 years with the mean age of (9.41 ± 4.29 years. To characterize the -511 T>C, -31 C>T, and IL-1RA polymorphisms, the PCR-RFLP and PCRVNTR methods were used. PCR was also used for the diagnosis of H. pylori and to determine whether cagA and vacA genes were present. Results: The histopathological analysis revealed 206 patients (54.6% with gastritis and 171 patients (45.4% with normal gastric tissue. Subjects carrying the -511 T/T genotype were associated with a risk of gastritis (odds ratio (OR = 2.75, 95% confidence interval (CI 1.45– 5.18, P = 0.0035. Similar results were found in subjects carrying -31 C/C (OR= 2.27, 95% CI 1.13–4.54, P = 0.0440. However, the IL-1RA polymorphism did not seem to be associated with gastric disease (OR= 1.38, 95% CI 0.58–3.26, P = 0.2400. Conclusions: This data suggests that IL-1β gene cluster polymorphisms and, more specifically, interactions between these polymorphisms and H. pylori may be predictors of gastritis risks, which possibly play a relevant role in the susceptibility to or the development of gastric disease early in life.

Helicobacter pylori and autoimmune disease: Cause or bystander

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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

Psychiatric symptoms and CAG expansion in Huntington`s disease

Energy Technology Data Exchange (ETDEWEB)

Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

1996-02-16

The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

Intact long-type DupA protein in Helicobacter pylori is an ATPase involved in multifunctional biological activities.

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Wang, Ming-yi; Chen, Cheng; Shao, Chen; Wang, Shao-bo; Wang, Ai-chu; Yang, Ya-chao; Yuan, Xiao-yan; Shao, Shi-he

2015-04-01

The function of intact long-type DupA protein in Helicobacter pylori was analyzed using immunoblotting and molecular biology techniques in the study. After cloning, expression and purification, ATPase activity of DupA protein was detected. Antibody was produced for localization and interaction proteins analysis. The dupA-deleted mutant was generated for adhesion and CagA protein translocation assay, susceptibility to different pH, IL-8 secretion assay, cytotoxicity to MKN-45 cells and proteins-involved apoptosis analysis. DupA protein exhibited an ATPase activity (129.5±17.8 U/mgprot) and located in bacterial membrane, while it did not involve the adhesion and CagA protein delivery of H. pylori. DupA protein involved the urease secretion as the interaction proteins. The wild type strain had a stronger growth in low pH than the dupA-deleted mutant (p DupA protein located in membrane as ATPase is a true virulence factor associated with duodenal ulcer development involving the IL-8 induction and urease secretion, while it inhibits gastric cancer cell growth in vitro by activating the mitochondria-mediated apoptotic pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Insights into the role of Helicobacter pylori infection in preeclampsia: from the bench to the bedside.

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Chiara eTersigni

2014-10-01

Full Text Available Preeclampsia (PE is defined as a hypertensive and coagulative disorder affecting about 2–8% of all pregnancies and it is one of the main causes of maternal and fetal morbidity and mortality. Despite the great amount of studies run in this field, little is known about the precise pathogenic mechanisms behind PE. While endothelial and trophoblast dysfunctions, exaggerated inflammatory response and hypercoagulative state have been shown to play a key role in the occurrence of PE, the primary trigger is still unknown. One of the hypotheses is that some infectious agents may represent a trigger for PE onset. Consistently, higher seroprevalence of Helicobacter pylori (HP infection, a Gram-negative bacterium with a specific tropism for human gastric mucosa, has been shown in women with PE. Even tighter association has been found between PE and infection with CagA (Cytotoxin-associated gene-A -positive strains of HP. Recent in vitro studies have shown that anti-CagA antibodies cross-react with human trophoblast cells and determine a functional impairment in terms of cell invasiveness, thus, providing the first pathogenic model of HP infection-mediated placental damage. Since in the early process of implantation and placental development, trophoblast invasion of maternal decidua is a crucial step, the proposed autoimmune mechanism induced by HP infection, negatively interfering with the fetal side of the early developing placenta, may represent a mechanism explaining the higher seropositivity for HP infection among PE women. However, the contribution of HP infection to the pathogenesis of PE or to the worsening of its clinical presentation needs to be further investigated as well as the possible impact of pre-pregnacy screening and eradication of HP infection on the incidence of the syndrome.

Helicobacter pylori infection and iron deficiency in teenage females in New Zealand.

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Fraser, Alan G; Scragg, Robert; Schaaf, David; Metcalf, Patricia; Grant, Cameron C

2010-04-30

Iron deficiency is an important problem in New Zealand children and young adults. Iron deficiency and Helicobacter pylori (H. pylori) infection are each more common in Māori and Pacific Island ethnic groups. This study seeks to determine if H. pylori infection is associated with iron deficiency. 792 female students from 7 Auckland high schools (median age 16 years) had H. pylori serology and tests for iron deficiency assessed by a combination of serum ferritin, iron saturation and mean cell volume. The prevalence of positive H. pylori serology was highest for Pacific Island students (49.0%; CI 38.0-60.0), intermediate for Māori (26.7%; CI 16.9-36.4) and Asian (24.7%; CI 12.6-36.7) and lowest for European (13.7%; 6.0-21.4) piron saturation (p=0.013), but not of ferritin (p=0.068), haemoglobin (p=0.08) or mean cell volume (p=0.16), compared to those with negative serology. Positive H. pylori serology was associated with increased risk of iron deficiency (RR 1.20; CI 1.08-1.34), but not anaemia (RR 1.01; CI 0.87-1.18), after adjusting for age, ethnicity and school SES decile. This study indicates that H. pylori infection is associated with iron deficiency in adolescent females. There are significant differences in H. pylori serology amongst different ethnic groups in New Zealand.

Helicobacter pylori Outer Membrane Protein 18 (Hp1125 Is Involved in Persistent Colonization by Evading Interferon-γ Signaling

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Yuqun Shan

2015-01-01

Full Text Available Outer membrane proteins (OMPs can induce an immune response. Omp18 (HP1125 of H. pylori is a powerful antigen that can induce significant interferon-γ (IFN-γ levels. Previous studies have suggested that IFN-γ plays an important role in H. pylori clearance. However, H. pylori has multiple mechanisms to avoid host immune surveillance for persistent colonization. We generated an omp18 mutant (H. pylori 26695 and H. pylori SS1 strain to examine whether Omp18 interacts with IFN-γ and is involved in H. pylori colonization. qRT-PCR revealed that IFN-γ induced Omp18 expression. qRT-PCR and western blot analysis revealed reduced expressions of virulence factors CagA and NapA in H. pylori 26695 with IFN-γ treatment, but they were induced in the Δomp18 strain. In C57BL/6 mice infected with H. pylori SS1 and the Δomp18 strain, the Δomp18 strain conferred defective colonization and activated a stronger inflammatory response. Signal transducer phosphorylation and transcription 1 (STAT1 activator was downregulated by the wild-type strain but not the Δomp18 strain in IFN-γ-treated macrophages. Furthermore, Δomp18 strain survival rates were poor in macrophages compared to the wild-type strain. We concluded that H. pylori Omp18 has an important function influencing IFN-γ-mediated immune response to participate in persistent colonization.

Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer

International Nuclear Information System (INIS)

Liu, Ningning; Zhou, Ning; Chai, Ni; Liu, Xuan; Jiang, Haili; Wu, Qiong; Li, Qi

2016-01-01

Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development. To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells. H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor–node–metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway. The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers

Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients.

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Gomes, Luciana I; Rocha, Gifone A; Rocha, Andreia M C; Soares, Taciana F; Oliveira, Celso A; Bittencourt, Paulo F S; Queiroz, Dulciene M M

2008-04-01

Duodenal ulcer-promoting gene (dupA) was recently described as a new putative Helicobacter pylori virulence marker associated with an increased risk for duodenal ulcer and reduced risk for gastric carcinoma in Japan and Korea. Since differences regarding the association among H. pylori markers and H. pylori-associated diseases have been demonstrated around the world, we evaluated the presence of the gene in 482 strains from Brazilian children (34 with duodenal ulcer and 97 with gastritis) and adults (126 with duodenal ulcer, 144 with gastritis and 81 with gastric carcinoma) by PCR using the described primers and an additional set of primers based on Brazilian strain sequences. The results were confirmed by sequencing. The presence of cagA was investigated by PCR and also included in the analysis. dupA was present in 445 (92.32%) and absent in 29 (6.02%) strains. All samples from children with and without duodenal ulcer were dupA-positive (p=1.0). No association was observed among the strains from adults with gastritis (92.36%), duodenal ulcer (87.30%, p=0.30) and gastric carcinoma (87.65%, p=0.31). Conversely, cagA-positve status remained independently associated with duodenal ulcer (children: odds ratios (OR)=5.58, 95% confidence intervals (CI)=1.67-18.50; adults: OR=3.33, 95% CI=2.14-5.19) and gastric carcinoma (OR=6.58, 95% CI=3.51-12.30) in multivariate analyses. The presence of dupA was significantly higher in strains from children than in those from adults (p=0.01). In conclusion, dupA is highly frequent and not associated with H. pylori-associated diseases in both Brazilian adults and children, which points to regional differences in the distribution of the gene.

Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies.

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Adamu, Mariam Abdullahi; Weck, Melanie Nicole; Gao, Lei; Brenner, Hermann

2010-07-01

Chronic atrophic gastritis (CAG) is an important precursor lesion of intestinal gastric cancer. As it is typically asymptomatic, epidemiological data on the incidence of CAG are sparse. We aimed to provide an overview of published data on CAG incidence (overall and according to risk factors) from follow-up studies. Articles with information on incidence of CAG published in English until 26th of July 2009 were identified through a systematic MEDLINE and EMBASE search. Data extracted include study characteristics and key findings regarding the incidence of CAG. A meta-analysis was performed on the association between Helicobacter pylori infection and CAG incidence. Overall, data on CAG incidence were available from 14 studies, in 7 studies incidence could be estimated according to H. pylori infection. Most studies were conducted in symptomatic or high risk populations and the maximum number of incident cases was 284. Incidence estimates ranged from 0 to 11% per year and were consistently below 1% in patients not infected with H. pylori. The highest incidence was observed in a special study conducted on ulcer patients treated by proximal gastric vagotomy. Rate ratios for the association between H. pylori infection and CAG incidence ranged from 2.4 to 7.6 with a summary estimate of 5.0 (95% confidence interval: 3.1-8.3). Incidence of CAG is very low in the absence of H. pylori infection. There is a need for more population-based studies to provide comparable estimates of incidence and the impact of risk factors in the development of CAG.

Phasevarion mediated epigenetic gene regulation in Helicobacter pylori.

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Yogitha N Srikhanta

Full Text Available Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression. In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M system, controls expression of a phase-variable regulon of genes (a "phasevarion", via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates. Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis.

The expression of Helicobacter pylori tfs plasticity zone cluster is regulated by pH and adherence, and its composition is associated with differential gastric IL-8 secretion.

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Silva, Bruno; Nunes, Alexandra; Vale, Filipa F; Rocha, Raquel; Gomes, João Paulo; Dias, Ricardo; Oleastro, Mónica

2017-08-01

Helicobacter pylori virulence is associated with different clinical outcomes. The existence of an intact dupA gene from tfs4b cluster has been suggested as a predictor for duodenal ulcer development. However, the role of tfs plasticity zone clusters in the development of ulcers remains unclear. We studied several H. pylori strains to characterize the gene arrangement of tfs3 and tfs4 clusters and their impact in the inflammatory response by infected gastric cells. The genome of 14 H. pylori strains isolated from Western patients, pediatric (n=10) and adult (n=4), was fully sequenced using the Illumina platform MiSeq, in addition to eight pediatric strains previously sequenced. These strains were used to infect human gastric cells, and the secreted interleukin-8 (IL-8) was quantified by ELISA. The expression of virB2, dupA, virB8, virB10, and virB6 was assessed by quantitative PCR in adherent and nonadherent fractions of H. pylori during in vitro co-infection, at different pH values. We have found that cagA-positive H. pylori strains harboring a complete tfs plasticity zone cluster significantly induce increased production of IL-8 from gastric cells. We have also found that the region spanning from virB2 to virB10 genes constitutes an operon, whose expression is increased in the adherent fraction of bacteria during infection, as well as in both adherent and nonadherent fractions at acidic conditions. A complete tfs plasticity zone cluster is a virulence factor that may be important for the colonization of H. pylori and to the development of severe outcomes of the infection with cagA-positive strains. © 2017 John Wiley & Sons Ltd.

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

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Santos, J.C. [Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, SP (Brazil); Ladeira, M.S.P. [Departamento de Patologia, Universidade Estadual Paulista, Botucatu, SP (Brazil); Pedrazzoli, J. Jr.; Ribeiro, M.L. [Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Bragança Paulista, SP (Brazil)

2012-06-22

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA{sup +} was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the X{sup 2} test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

International Nuclear Information System (INIS)

Santos, J.C.; Ladeira, M.S.P.; Pedrazzoli, J. Jr.; Ribeiro, M.L.

2012-01-01

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA + was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the X 2 test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

Directory of Open Access Journals (Sweden)

J.C. Santos

2012-09-01

Full Text Available It is well known that the risk of development of gastric cancer (GC in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA+ was determined by the polymerase chain reaction (PCR as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the χ² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively and the IL-1β -511 C/C genotype was associated with GC (P = 0.03. The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.

Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

DEFF Research Database (Denmark)

Norn, Svend

2007-01-01

Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytoki......Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load...... and the proliferative marker Ki-67. H. pylori infection, bacteria load and inflammatory activity were associated with increased cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53 was significantly correlated to IFN-γ, IL-8 and IL-10. The H. pylori-positive state was furthermore accompanied...... of the gastrointestinal tract, such studies in cell turnover may provide insights valuable in the investigations of potential precursors of gastric malignancies....

Helicobacter pylori moves through mucus by reducing mucin viscoelasticity

OpenAIRE

Celli, Jonathan P.; Turner, Bradley S.; Afdhal, Nezam H.; Keates, Sarah; Ghiran, Ionita; Kelly, Ciaran P.; Ewoldt, Randy H.; McKinley, Gareth H.; So, Peter; Erramilli, Shyamsunder; Bansil, Rama

2009-01-01

The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner in which H. pylori is able to swim through the viscoelastic mucus gel that coats the stomach wall remains poorly understood. Previous rheology studies on gastric mucin, the key...

"Targeted disruption of the epithelial-barrier by Helicobacter pylori"

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Wroblewski Lydia E

2011-11-01

Full Text Available Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier.

Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

DEFF Research Database (Denmark)

Holck, Susanne; Holm, I.L.; Holck, P.P.

2007-01-01

Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytoki...

Clinical relevance of the cagA, tnpA and tnpB genes in Helicobacter pylori

NARCIS (Netherlands)

Abadi, Amin Talebi Bezmin; Mobarez, Ashraf Mohhabati; Bonten, Marc J M; Wagenaar, Jaap A; Kusters, Johannes G

2014-01-01

BACKGROUND: Numerous proteins have been proposed as virulence factors for the gram negative gastric bacterium Helicobacter pylori but only for a few this has unequivocally been demonstrated. The aim of the current study was to evaluate the association of the putative virulence factors tnpA and tnpB

Helicobacter pylori neutrophil-activating protein: A potential Treg modulator suppressing allergic asthma?

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Anjna eSehrawat

2015-06-01

Full Text Available The ultimate aim of immunology is to kill the pathogen without being harmful to the host. But what if eliminating the pathogen in itself is discomforting for the host? One such emerging case is of Helicobacter pylori. Modern medicine, infantile vaccination and ultra-hygienic conditions have led to progressive disappearance of H. pylori in different parts of the world. However, the adversities caused by H. pylori’s absence are much larger than those caused by its presence. Asthma is rising as an epidemic in last few decades and several reports suggest an inverse-relationship between H. pylori’s persistence and early-life onset asthma. Regulatory T cells play an important role in both the cases. This is further supported by experiments on mouse-models. Hence, need of the hour is to discern the relationship between H. pylori and its host and eliminating its negative impacts without disturbing our indigenous microbiota. To resolve whether H. pylori is a pathogen or an amphibiont is another important side. This review explores the biological basis of H. pylori-induced priming of immune system offering resistance to childhood-onset asthma. HP-NAP-Tregs interaction has been predicted using molecular docking and dynamic simulation.

Piperine treatment suppresses Helicobacter pylori toxin entry in to gastric epithelium and minimizes β-catenin mediated oncogenesis and IL-8 secretion in vitro

Science.gov (United States)

Tharmalingam, Nagendran; Park, Min; Lee, Min Ho; Woo, Hyun Jun; Kim, Hyun Woo; Yang, Ji Yeong; Rhee, Ki-Jong; Kim, Jong-Bae

2016-01-01

Helicobacter pylori related gastric cancer initiation has been studied widely. The objective of our present study was to evaluate the effect of a single compound piperine on H. pylori infection and its anti-inflammatory and anti-cancer effects in vitro. Cytotoxicity was tested by Ez-cytox cell viability assay kit. Effects of piperine on H. pylori toxin gene expression and IL-8 expression in mammalian cells during infection were assessed by RT-PCR. Effects of piperine on toxin entry into host cells, E-cadherin cleavage by H. pylori, and the changes in H. pylori mediated β-catenin expression and IL-8 secretion were determined by immunoblotting. Piperine treatment restrained the entry of CagA and VacA into AGS cells. Piperine administration in H. pylori infection reduced E-cadherin cleavage in stomach epithelium. In addition, H. pylori induced β-catenin up-regulation was reduced. Piperine administration impaired IL-8 secretion in H. pylori-infected gastric epithelial cells. As we reported previously piperine restrained H. pylori motility. The possible reason behind the H. pylori inhibition mechanism of piperine could be the dwindled motility, which weakened H. pylori adhesion to gastric epithelial cells. The reduced adhesion decreased the toxin entry thereby secreting less amount of IL-8. In addition, piperine treatment suppressed H. pylori protease led to reduction of E-cadherin cleavage and β-catenin expression resulting in diminished β-catenin translocation into the nucleus thus decreasing the risk of oncogenesis. To our knowledge, this is the preliminary report of piperine mediated H. pylori infection control on gastric epithelial cells in-vitro. PMID:27158376

Prevalence of duodenal ulcer-promoting gene (dupA) of Helicobacter pylori in patients with duodenal ulcer in North Indian population.

Science.gov (United States)

Arachchi, H S Jayasinghe; Kalra, Vijay; Lal, Banwari; Bhatia, Vikram; Baba, C S; Chakravarthy, S; Rohatgi, S; Sarma, Priyangshu M; Mishra, V; Das, Bimal; Ahuja, Vineet

2007-12-01

The duodenal ulcer (DU)-promoting gene (dupA) of Helicobacter pylori has been identified as a novel virulent marker associated with an increased risk for DU. The presence or absence of dupA gene of H. pylori present in patients with DU and functional dyspepsia in North Indian population was studied by polymerase chain reaction (PCR) and hybridization analysis. One hundred and sixty-six patients (96 DU and 70 functional dyspepsia) were included in this study. In addition, sequence diversity of dupA gene of H. pylori found in these patients was analyzed by sequencing the PCR products jhp0917 and jhp0918 on both strands with appropriate primers. PCR and hybridization analyses indicated that dupA gene was present in 37.5% (36/96) of H. pylori strains isolated from DU patients and 22.86% (16/70) of functional dyspepsia patients (p dupA was significantly associated with the cagA-positive genotype (p dupA gene with DU in this population. The dupA gene can be considered as a novel virulent marker for DU in this population.

Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population.

Science.gov (United States)

Tay, Chin Yen; Mitchell, Hazel; Dong, Quanjiang; Goh, Khean-Lee; Dawes, Ian W; Lan, Ruiting

2009-06-19

Helicobacter pylori is a major gastric bacterial pathogen. This pathogen has been shown to follow the routes of human migration by their geographical origin and currently the global H. pylori population has been divided into six ancestral populations, three from Africa, two from Asia and one from Europe. Malaysia is made up of three major ethnic populations, Malay, Chinese and Indian, providing a good population for studying recent H. pylori migration and admixture. Seventy eight H. pylori isolates, including 27 Chinese, 35 Indian and 16 Malay isolates from Malaysia were analysed by multilocus sequence typing (MLST) of seven housekeeping genes and compared with the global MLST data. STRUCTURE analysis assigned the isolates to previously identified H. pylori ancestral populations, hpEastAsia, hpAsia2 and hpEurope, and revealed a new subpopulation, hspIndia, within hpAsia2. Statistical analysis allowed us to identify population segregation sites that divide the H. pylori populations and the subpopulations. The majority of Malay isolates were found to be grouped together with Indian isolates. The majority of the Malay and Indian H. pylori isolates share the same origin while the Malaysian Chinese H. pylori is distinctive. The Malay population, known to have a low infection rate of H. pylori, was likely to be initially H. pylori free and gained the pathogen only recently from cross infection from other populations.

Significant Reduction in Helicobacter pylori Load in Humans with Non-viable Lactobacillus reuteri DSM17648: A Pilot Study.

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Holz, Caterina; Busjahn, Andreas; Mehling, Heidrun; Arya, Stefanie; Boettner, Mewes; Habibi, Hajar; Lang, Christine

2015-06-01

Reducing the amount of Helicobacter pylori in the stomach by selective bacterial-bacterial cell interaction was sought as an effective and novel method for combating the stomach pathogen. Lactobacillus reuteri DSM17648 was identified as a highly specific binding antagonist to H. pylori among more than 700 wild-type strains of Lactobacillus species. Applying a stringent screening procedure, the strain DSM17648 was identified as selective binder to H. pylori cells under in vivo gastric conditions. The strain DSM17648 co-aggregates the pathogen in vivo and in vitro. The specific co-aggregation occurs between Lact. reuteri DSM17648 and different H. pylori strains and serotypes, as well as H. heilmannii, but not with Campylobacter jejuni or other commensal oral and intestinal bacteria. Lact. reuteri DSM17648 was shown in a proof-of-concept single-blinded, randomized, placebo-controlled pilot study to significantly reduce the load of H. pylori in healthy yet infected adults. Reducing the amount of H. pylori in the stomach by selective bacterial-bacterial cell interaction might be an effective and novel method for combating the stomach pathogen. Lact. reuteri DSM17648 might prove useful as an adhesion blocker in antibiotic-free H. pylori therapies.

[The effect of Helicobacter pylori eradication on chronic gastritis].

Science.gov (United States)

Kodama, Masaaki; Murakami, Kazunari; Okimoto, Tadayoshi; Fujioka, Toshio

2013-08-01

Helicobacter pylori (H. pylori) is a major pathogen of chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Atrophic gastritis and intestinal metaplasia are recognized as precancerous lesion of gastric cancer. Many studies reported that H. pylori eradication had the preventive effect of gastric cancer. Moreover many studies mentioned the improvement of gastric atrophy and/or intestinal metaplasia. Two meta-analysis indicated the improvement of atrophic gastritis but not of intestinal metaplasia. In our study, intestinal metaplasia improved at lesser curvature of the corpus six years after eradication. H. pylori eradication has benefit for gastric cancer prevention provably due to improvement of the precancerous lesion such as atrophic gastritis and intestinal metaplasia. Especially, H. pylori eradication before the appearance of atrophy and intestinal metaplasia has been considered to be effective in inhibiting the development of gastric cancer. Therefore, improvement or elimination of chronic gastritis with H. pylori eradication might have possibility of gastric cancer inhibition.

NikR mediates nickel-responsive transcriptional induction of urease expression in Helicobacter pylori

NARCIS (Netherlands)

A.H.M. van Vliet (Arnoud); S.W. Poppelaars (Sophie); B.J. Davies; J. Stoof (Jeroen); S. Bereswill (Stefan); M. Kist (Manfred); C.W. Penn (Charles); E.J. Kuipers (Ernst); J.G. Kusters (Johannes)

2002-01-01

textabstractThe important human pathogen Helicobacter pylori requires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity of H. pylori urease were previously demonstrated to be induced by

CpG island methylator phenotype, Helicobacter pylori, Epstein-Barr virus, and microsatellite instability and prognosis in gastric cancer: a systematic review and meta-analysis.

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Liang Zong

Full Text Available BACKGROUND: The controversy of CpG island methylator phenotype (CIMP in gastric cancer persists, despite the fact that many studies have been conducted on its relation with helicobacter pylori (H. pylori, Epstein-Barr virus (EBV, and microsatellite instability (MSI and prognosis. To drive a more precise estimate of this postulated relationship, a meta-analysis was performed based on existing relevant studies. METHODS: We combined individual patient data from 12 studies which involved 1000 patients with gastric cancer, which met the criteria. We tabulated and analyzed parameters from each study, including H. pylori, EBV, MSI, and clinical information of patients. RESULTS: The overall OR for H. pylori infection in CIMP positive group vs. negative group revealed that significantly elevated risks of positive H. pylori infection in the former were achieved (OR 2.23 95% CI, 1.25-4.00; P = 0.007, Pheterogeneity = 0.05. Similarly, strong relation between EBV infection and CIMP was achieved by OR 51.27 (95% CI, 9.39-279.86; P<0.00001, Pheterogeneity = 0.39. The overall OR for MSI in CIMP positive group vs. negative group was 4.44 (95% CI, 1.17-16.88; P = 0.03, Pheterogeneity = 0.01. However, there did not appear to be any correlations with clinical parameters such as tumor site, pathological type, cell differentiation, TNM stage, distant metastasis, lymph node metastasis, and 5-year survival. CONCLUSIONS: The meta-analysis highlights the strong relation of CIMP with H. pylori, EBV, and MSI, but CIMP can not be used as a prognostic marker for gastric cancer.

Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

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Yang Yao-Jong

2012-03-01

Full Text Available Abstract Background H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways. Results Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100 of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting. Conclusions H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population

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Dawes Ian W

2009-06-01

Full Text Available Abstract Background Helicobacter pylori is a major gastric bacterial pathogen. This pathogen has been shown to follow the routes of human migration by their geographical origin and currently the global H. pylori population has been divided into six ancestral populations, three from Africa, two from Asia and one from Europe. Malaysia is made up of three major ethnic populations, Malay, Chinese and Indian, providing a good population for studying recent H. pylori migration and admixture. Results Seventy eight H. pylori isolates, including 27 Chinese, 35 Indian and 16 Malay isolates from Malaysia were analysed by multilocus sequence typing (MLST of seven housekeeping genes and compared with the global MLST data. STRUCTURE analysis assigned the isolates to previously identified H. pylori ancestral populations, hpEastAsia, hpAsia2 and hpEurope, and revealed a new subpopulation, hspIndia, within hpAsia2. Statistical analysis allowed us to identify population segregation sites that divide the H. pylori populations and the subpopulations. The majority of Malay isolates were found to be grouped together with Indian isolates. Conclusion The majority of the Malay and Indian H. pylori isolates share the same origin while the Malaysian Chinese H. pylori is distinctive. The Malay population, known to have a low infection rate of H. pylori, was likely to be initially H. pylori free and gained the pathogen only recently from cross infection from other populations.

Association of polymorphisms in virulence factor of Helicobacter pylori and gastroduodenal diseases in South Korea.

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Kim, Ji Yeon; Kim, Nayoung; Nam, Ryoung Hee; Suh, Ji Hyung; Chang, Hyun; Lee, Jung Won; Kim, Young Sun; Kim, Jung Mogg; Choi, Jae Won; Park, Jung Geun; Lee, Yeon Suk; Lee, Dong Ho; Jung, Hyun Chae

2014-05-01

Clinical outcomes of Helicobacter pylori (HP) infection have been shown to be dependent on the variability of virulence factors. The aim of this study was to evaluate the prevalence of each virulence factor and the association between polymorphisms of the virulence factors of HP, and the clinical outcome of gastroduodenal diseases in South Korea. Four hundred one HP colonies were analyzed (75 colonies from 45 controls; 71 colonies from 39 benign gastric ulcer [BGU] patients; 102 colonies from 54 duodenal ulcer [DU] patients; 121 colonies from 77 stomach cancer patients; and 32 colonies from 25 dysplasia patients). Polymerase chain reaction amplifications for vacA, cagA, iceA, oipA, and dupA were performed using DNA extract from HP isolates cultured from mucosal biopsy specimens. dupA was regarded as positive when all of jph0718, jph0719, and dupA were positive. Most colonies were composed of vacA s1 (100.0%), i1 (100.0%) and m1 (92.9%), cagA-positive (87.2%), iceA1 (95.8%), oipA-positive (91.2%), and dupA-negative (52.0%) genotypes. dupA was more frequently expressed in BGU (81.3%), DU (74.7%), and dysplasia (41.7%) than control (16.7%) (P dupA-positive HP showed an increased risk of BGU (odds ratio 33.06, 95% confidence interval 11.91-91.79) and DU (odds ratio 15.60, 95% confidence interval 6.49-37.49). HP infection in South Koreans appears to be closely related to highly virulent strains (vacA s1/i1/m1, cagA(+), iceA1(+), and oipA(+)), except dupA. dupA has an intimate association with the development of peptic ulcer diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia and identification of a Maori-tribe type strain: a cross sectional study.

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Miftahussurur, Muhammad; Tuda, Josef; Suzuki, Rumiko; Kido, Yasutoshi; Kawamoto, Fumihiko; Matsuda, Miyuki; Tantular, Indah S; Pusarawati, Suhintam; Nasronudin; Harijanto, Paul N; Yamaoka, Yoshio

2014-01-01

Sulawesi in Indonesia has a unique geographical profile with assumed separation from Sundaland. Studies of Helicobacter pylori in this region are rare due to the region's rural location and lack of endoscopy equipment. Indirect methods are, therefore, the most appropriate for measuring H. pylori infection in these areas; with the disposable gastric brush test, we can obtain gastric juice as well as small gastric tissue samples for H. pylori culture. We investigated the prevalence of H. pylori infection and evaluated human migration patterns in the remote areas of North Sulawesi. We recruited a total of 251 consecutive adult volunteers and 131 elementary school children. H. pylori infection was determined by urine antibody test. A gastric brush test was used to culture H. pylori. We used next-generation and polymerase chain reaction based sequencing to determine virulence factors and multi-locus sequence typing (MLST). The overall H. pylori prevalence was only 14.3% for adults and 3.8% for children, and 13.6% and 16.7% in Minahasanese and Mongondownese participants, respectively. We isolated a single H. pylori strain, termed -Manado-1. Manado-1 was East Asian type cagA (ABD type), vacA s1c-m1b, iceA1 positive/iceA2 negative, jhp0562-positive/β-(1,3) galT-negative, oipA "on", and dupA-negative. Phylogenetic analyses showed the strain to be hspMaori type, a major type observed in native Taiwanese and Maori tribes. Our data support that very low H. pylori infection prevalence in Indonesia. Identification of hspMaori type H. pylori in North Sulawesi may support the hypothesis that North Sulawesi people migrated from north.

Phenotypic and genotypic characterization of Helicobacter pylori from patients with and without peptic ulcer disease

DEFF Research Database (Denmark)

Petersen, A M; Fussing, V; Colding, H

2000-01-01

BACKGROUND: Helicobacter pylori plays an important role in peptic ulcer disease, although not all H. pylori-infected persons will develop a peptic ulcer. Currently, H. pylori strains cannot be divided into commensals and pathogens. METHODS: Fifty H. pylori strains were cultured from patients......) profile of H. pylori strains were recorded; randomly amplified polymorphic DNA (RAPD) and urease gene typing were performed and correlated with diagnostic groups. RESULTS: Electron micrographs showed that H. pylori strains from patients with gastric ulcers adhered more frequently through filamentous...... strands and were less frequently found free in mucus than any other diagnostic group (P pylori strains from patients with gastric...

Original Article

African Journals Online (AJOL)

Conclusion: H. pylori infection with cagA positive strains was similarly common in dyspeptic diabetic patients and controls. It was associated with poorer glycemic control and higher rates of microalbuminuria in diabetic subjects. Key words: cagA positive strains; Diabetes mellitus;. Helicobatcer pylori; Microalbuminuria.

Rickettsial pathogens and arthropod vectors of medical and veterinary significance on Kwajalein Atoll and Wake Island

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Durden, L.

2012-05-01

Full Text Available Modern surveys of ectoparasites and potential vector-borne pathogens in the Republic of the Marshall Islands and Wake Island are poorly documented. We report on field surveys of ectoparasites from 2010 with collections from dogs, cats, and rats. Five ectoparasites were identified: the cat flea Ctenocephalides felis, a sucking louse Hoplopleura pacifica, the mites Laelaps nuttalli and Radfordia ensifera, and the brown dog tickRhipicephalus sanguineus. Ectoparasites were screened for rickettsial pathogens. DNA from Anaplasma platys, a Coxiella symbiont of Rhipicephalus sanguineus, anda Rickettsia sp. were identified by PCR and DNA sequencing from ticks and fleas on Kwajalein Atoll. An unidentified spotted fever group Rickettsia was detected in a pool of Laelaps nuttalli and Hoplopleura pacifica from Wake Island. The records of Hoplopleura pacifica, Laelaps nuttalli, and Radfordia ensifera and the pathogens are new for Kwajalein Atoll and Wake Island.

Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis.

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Yoshida, Takeichi; Kato, Jun; Maekita, Takao; Yamashita, Satoshi; Enomoto, Shotaro; Ando, Takayuki; Niwa, Tohru; Deguchi, Hisanobu; Ueda, Kazuki; Inoue, Izumi; Iguchi, Mikitaka; Tamai, Hideyuki; Ushijima, Toshikazu; Ichinose, Masao

2013-10-01

Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer. Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II. Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation. Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.

Frequency of periodontal pathogens and Helicobacter pylori in the mouths and stomachs of obese individuals submitted to bariatric surgery: a cross-sectional study

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PATARO, André Luiz; CORTELLI, Sheila Cavalca; ABREU, Mauro Henrique Nogueira Guimarães; CORTELLI, José Roberto; FRANCO, Gilson Cesar Nobre; AQUINO, Davi Romeiro; COTA, Luis Otavio Miranda; COSTA, Fernando Oliveira

2016-01-01

ABSTRACT Objectives This cross-sectional study compared the frequency of oral periodontopathogens and H. pylori in the mouths and stomachs of obese individuals with or without periodontitis submitted to bariatric surgery. Material and Methods One hundred and fifty-four men and women aged 18-65 were conveniently distributed into four groups. Two groups were composed of individuals who underwent bariatric surgery with (BP) (n=40) and without (BNP) (n=39) periodontitis and two obese control groups with (CP) (n=35) and without (CNP) (n=40) periodontitis. The oral pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Parvimonas micra, Treponema denticola, Tannerella forsythia, Campylobacter rectus, and Helicobacter pylori were detected by a polymerase chain reaction technique using saliva, tongue and stomach biopsy samples. Results Statistical analysis demonstrated that periodontopathogens were highly frequent in the mouth (up to 91.4%). In the bariatric surgically treated group, orally, P. gingivalis, T. denticola and T. forsythia were more frequent in periodontitis, while C. rectus was more frequent in non-periodontitis subjects. Stomach biopsies also revealed the high frequency of five oral species in both candidates for bariatric surgery (91.6%) and the bariatric (83.3%) groups. H. pylori was frequently detected in the mouth (50.0%) and stomach (83.3%). In the stomach, oral species and H. pylori appeared in lower frequency in the bariatric group. Conclusions Obese individuals showed high frequencies of periodontopathogens and H. pylori in their mouths and stomachs. Bariatric surgery showed an inverse microbial effect on oral and stomach environments by revealing higher oral and lower stomach bacterial frequencies. PMID:27383704

Application of methylation in improving plasmid transformation into Helicobacter pylori.

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Zhao, Huilin; Xu, Linlin; Rong, Qianyu; Xu, Zheng; Ding, Yunfei; Zhang, Ying; Wu, Yulong; Li, Boqing; Ji, Xiaofei

2018-05-23

Helicobacter pylori is an important gastrointestinal pathogen. Its strains possess different levels of powerful restriction modification systems, which are significant barriers to genetic tools used for studying the role of functional genes in its pathogenesis. Methylating vectors in vitro was reported as an alternative to overcome this barrier in several bacteria. In this study we used two H. pylori-E. coli shuttle plasmids and several single/double-crossover homologous recombination gene-targeting plasmids, to test the role of methylation in H. pylori transformation. According to our results, transformants could be obtained only after shuttle plasmids were methylated before transformation. It is helpful in gene complementation and over-expression although at a low frequency. The frequency of gene-targeting transformation was also increased after methylation, especially for the single-crossover recombination plasmids, the transformants of which could only be obtained after methylation. For the double-crossover recombination targeting plasmids, the initial yield of transformants was 0.3-0.8 × 10 2 CFUs per microgram plasmid DNA. With the help of methylation, the yield was increased to 0.4-1.3 × 10 2 CFUs per microgram plasmid DNA. These results suggest that in vitro methylation can improve H. pylori transformation by different plasmids, which will benefit the pathogenic mechanism research. Copyright © 2018. Published by Elsevier B.V.

[Overview of researches for Helicobacter pylori in oral cavity and stomach].

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Yang, Kaiyu; Li, Yuqing; Zhou, Xuedong

2014-06-01

Helicobacter pylori (H. pylori) is one of the most common pathogens in human and it is closely related to gastrointestinal diseases. It is essential for us to understand the transmission process of H. pylori to prevent its spreading. The oral cavity has been proposed as a reservoir for gastric H. pylori, which has been detected by culture and polymerase chain reaction (PCR) in both dental plaque and saliva. Some researchers have proposed H. pylori in oral cavity may play an important role in its transmission and reinfection. Oral-oral or fecal-oral transmission are thought to be the most possible transmit way. This review will discuss the evidence for the role of the oral cavity in the transmission of H. pylori, the difficulties encountered in addressing this topic and possible directions for future research. Oral H. pylori may also play a role in the diagnosis and prevention of deceases related to H. pylori such as gastritis, gastric ulcer and gastric carcinoma. The recent progresses in this area are also reviewed. Moreover, we also discussed the relationship between oral H. pylori and oral deceases like periodontal disease and oral ulcer.

Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains.

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Argemi, Xavier; Nanoukon, Chimène; Affolabi, Dissou; Keller, Daniel; Hansmann, Yves; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

2018-02-25

Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus ; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8-89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes ( hsrA and dfrG , respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus . Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis .

Comparative Genomics and Identification of an Enterotoxin-Bearing Pathogenicity Island, SEPI-1/SECI-1, in Staphylococcus epidermidis Pathogenic Strains

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Xavier Argemi

2018-02-01

Full Text Available Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8–89.7% nucleotide similarity. Various other plasmids were identified, particularly p_3_95 and p_4_95, which carry antibiotic resistance genes (hsrA and dfrG, respectively, and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus. Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB_AbaM_IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis.

Unique mechanism of Helicobacter pylori for colonizing the gastric mucus.

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Yoshiyama, H; Nakazawa, T

2000-01-01

Helicobacter pylori is a human gastric pathogen causing chronic infection. Urease and motility using flagella are essential factors for its colonization. Urease of H. pylori exists both on the surface and in the cytoplasm, and is involved in neutralizing gastric acid and in chemotactic motility. H. pylori senses the concentration gradients of urea in the gastric mucus layer, then moves toward the epithelial surface by chemotactic movement. The energy source for the flagella movement is the proton motive force. The hydrolysis of urea by the cytoplasmic urease possibly generates additional energy for the flagellar rotation in the mucus gel layer.

How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

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Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

2016-09-01

The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

Antibody reactivity against Helicobacter pylori proteins in a sample of the Spanish adult population in 2008-2013.

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Fernández-de-Larrea, Nerea; Michel, Angelika; Romero, Beatriz; Butt, Julia; Pawlita, Michael; Pérez-Gómez, Beatriz; Castaño-Vinyals, Gemma; Moreno, Victor; Martín, Vicente; Amiano, Pilar; Castilla, Jesús; Fernández-Tardón, Guillermo; Dierssen-Sotos, Trinidad; Clofent, Juan; Alguacil, Juan; Huerta, José María; Jiménez-Moleón, José Juan; Barricarte, Aurelio; Molinuevo, Amaia; Fernández-Villa, Tania; Casabonne, Delphine; Sierra, Ángeles; Kogevinas, Manolis; de Sanjosé, Silvia; Pollán, Marina; Del Campo, Rosa; Waterboer, Tim; Aragonés, Nuria

2017-10-01

Differences in Helicobacter pylori protein expression have been related to the risk of severe gastric diseases. In Spain, a marked geographic pattern in gastric cancer mortality has long been reported. To characterize antibody reactivity patterns against 16 H. pylori proteins, by age, sex, and region of birth, in a large sample of the Spanish adult population. Antibody reactivity was quantified by H. pylori multiplex serology in a sample from the control group of the multicase-control study MCC-Spain. For this analysis, 2555 population-based controls were included. Each participant was classified as seropositive or seronegative for each protein according to specific cutoffs. Overall H. pylori seroprevalence was defined as positivity against ≥4 proteins. Descriptive analyses by age, sex, and region of birth were performed for both seroprevalence and seroreactivity (continuous measure). Differences among groups were tested by logistic and linear regression models. Overall H. pylori seroprevalence increased with age in both sexes. For ages 55-74, seroprevalence was lower in women than in men (84% vs 92%, Ppylori seropositive subjects, proteins with the highest seroprevalence were GroEL, NapA, HP231, and Omp. Seropositivity for most of the proteins increased or remained stable with age, rising mainly for CagA, GroEL, and HyuA in women. A clear cohort effect was not observed. This is the first study to describe the antibody patterns against 16 H. pylori proteins in the Spanish population. We found variability in the H. pylori antibody profiles according to both individual factors such as age and sex, and environmental factors such as the region of birth. The slightness of the reduction in seropositivity with decreasing age highlights the ongoing importance of this infection. © 2017 John Wiley & Sons Ltd.

Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

LENUS (Irish Health Repository)

Kell, M R

2012-02-03

BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

Methods for detecting the environmental coccoid form of Helicobacter pylori

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Mahnaz eMazaheri Assadi

2015-05-01

Full Text Available 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.

Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota

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Yao-Jong Yang

2016-02-01

Full Text Available As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D. Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.

Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

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Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

2014-12-01

Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

Helicobacter pylori genomic microevolution during naturally occurring transmission between adults.

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Bodo Linz

Full Text Available The human gastric pathogen Helicobacter pylori is usually acquired during childhood and, in the absence of treatment, chronic infection persists through most of the host's life. However, the frequency and importance of H. pylori transmission between adults is underestimated. Here we sequenced the complete genomes of H. pylori strains that were transmitted between spouses and analysed the genomic changes. Similar to H. pylori from chronic infection, a significantly high proportion of the determined 31 SNPs and 10 recombinant DNA fragments affected genes of the hop family of outer membrane proteins, some of which are known to be adhesins. In addition, changes in a fucosyltransferase gene modified the LPS component of the bacterial cell surface, suggesting strong diversifying selection. In contrast, virulence factor genes were not affected by the genomic changes. We propose a model of the genomic changes that are associated with the transmission and adaptation of H. pylori to a new human host.

Conjugative type IVb pilus recognizes lipopolysaccharide of recipient cells to initiate PAPI-1 pathogenicity island transfer in Pseudomonas aeruginosa

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Pseudomonas aeruginosa pathogenicity island 1 (PAPI-1) is one of the largest genomic islands of this important opportunistic human pathogen. Previous studies have shown that PAPI-1 encodes several putative virulence factors, a major regulator of biofilm formation, and antibiotic-resistance traits, a...

Early-life family structure and microbially induced cancer risk.

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Martin J Blaser

2007-01-01

Full Text Available Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men.We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative, belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0 among those in a sibship of seven or more individuals than in a sibship of between one and three persons.These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

Early-life family structure and microbially induced cancer risk.

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Blaser, Martin J; Nomura, Abraham; Lee, James; Stemmerman, Grant N; Perez-Perez, Guillermo I

2007-01-01

Cancer may follow exposure to an environmental agent after many decades. The bacterium Helicobacter pylori, known to be acquired early in life, increases risk for gastric adenocarcinoma, but other factors are also important. In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men. We examined a long-term cohort of Japanese-American men followed for 28 y, and performed a nested case-control study among those carrying H. pylori or the subset carrying the most virulent cagA+ H. pylori strains to address whether family structure predicted cancer development. We found that among the men who were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H. pylori test is falsely negative), belonging to a large sibship or higher birth order was associated with a significantly increased risk of developing gastric adenocarcinoma late in life. For those with cagA+ strains, the risk of developing gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence interval 1.2-4.0) among those in a sibship of seven or more individuals than in a sibship of between one and three persons. These results provide evidence that early-life social environment plays a significant role in risk of microbially induced malignancies expressing five to eight decades later, and these findings lead to new models to explain these interactions.

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

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Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

2012-01-01

Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

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Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

2016-01-01

Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

Systems-wide analyses of mucosal immune responses to Helicobacter pylori at the interface between pathogenicity and symbiosis

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Kronsteiner, Barbara; Bassaganya-Riera, Josep; Philipson, Casandra; Viladomiu, Monica; Carbo, Adria; Abedi, Vida; Hontecillas, Raquel

2016-01-01

Abstract Helicobacter pylori is the dominant member of the gastric microbiota in over half of the human population of which 5–15% develop gastritis or gastric malignancies. Immune responses to H. pylori are characterized by mixed T helper cell, cytotoxic T cell and NK cell responses. The presence of Tregs is essential for the control of gastritis and together with regulatory CX3CR1+ mononuclear phagocytes and immune-evasion strategies they enable life-long persistence of H. pylori. This H. pylori-induced regulatory environment might contribute to its cross-protective effect in inflammatory bowel disease and obesity. Here we review host-microbe interactions, the development of pro- and anti-inflammatory immune responses and how the latter contribute to H. pylori's role as beneficial member of the gut microbiota. Furthermore, we present the integration of existing and new data into a computational/mathematical model and its use for the investigation of immunological mechanisms underlying initiation, progression and outcomes of H. pylori infection. PMID:26939848

Human lactoferrin increases Helicobacter pylori internalisation into AGS cells.

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Coray, Dorien S; Heinemann, Jack A; Tyrer, Peter C; Keenan, Jacqueline I

2012-05-01

Helicobacter pylori has high global infection rates and can cause other undesirable clinical manifestations such as duodenal ulcer (DU) and gastric cancer (GC). Frequencies of re-infection after therapeutic clearance and rates of DU versus GC vary geographically and differ markedly between developed and developing countries, which suggests additional factors may be involved. The possibility that, in vivo, lactoferrin (Lf) may play a subtle role in modulating micronutrient availability or bacterial internalisation with implications for disease etiology is considered. Lf is an iron binding protein produced in mammals that has antimicrobial and immunomodulatory properties. Some bacteria that regularly colonise mammalian hosts have adapted to living in high Lf environments and we investigated if this included the gastric pathogen H. pylori. We found that H. pylori was able to use iron from fully iron-saturated human Lf (hLf) whereas partially iron-saturated hLf (apo) did not increase H. pylori growth. Instead, apo-hLf increased adherence to and internalisation of bacteria into cultured epithelial cells. By increasing internalisation, we speculate that apo-human lactoferrin may contribute to H. pylori's ability to persistence in the human stomach, an observation that potentially has implications for the risk of H. pylori-associated disease.

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

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Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-01-01

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

Science.gov (United States)

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-03-28

To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12

Phylogenomics of Colombian Helicobacter pylori isolates.

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Gutiérrez-Escobar, Andrés Julián; Trujillo, Esperanza; Acevedo, Orlando; Bravo, María Mercedes

2017-01-01

During the Spanish colonisation of South America, African slaves and Europeans arrived in the continent with their corresponding load of pathogens, including Helicobacter pylori . Colombian strains have been clustered with the hpEurope population and with the hspWestAfrica subpopulation in multilocus sequence typing (MLST) studies. However, ancestry studies have revealed the presence of population components specific to H. pylori in Colombia. The aim of this study was to perform a thorough phylogenomic analysis to describe the evolution of the Colombian urban H. pylori isolates. A total of 115 genomes of H. pylori were sequenced with Illumina technology from H. pylori isolates obtained in Colombia in a region of high risk for gastric cancer. The genomes were assembled, annotated and underwent phylogenomic analysis with 36 reference strains. Additionally, population differentiation analyses were performed for two bacterial genes. The phylogenetic tree revealed clustering of the Colombian strains with hspWestAfrica and hpEurope, along with three clades formed exclusively by Colombian strains, suggesting the presence of independent evolutionary lines for Colombia. Additionally, the nucleotide diversity of horB and vacA genes from Colombian isolates was lower than in the reference strains and showed a significant genetic differentiation supporting the hypothesis of independent clades with recent evolution. The presence of specific lineages suggest the existence of an hspColombia subtype that emerged from a small and relatively isolated ancestral population that accompanied crossbreeding of human population in Colombia.

Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura?

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Every Alison L

2011-02-01

Full Text Available Abstract Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura. The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season, concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials.

Interaction of legionella pneumophila and helicobacter pylori with bacterial species isolated from drinking water biofilms

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Azevedo Nuno F

2011-03-01

Full Text Available Abstract Background It is well established that Legionella pneumophila is a waterborne pathogen; by contrast, the mode of Helicobacter pylori transmission remains unknown but water seems to play an important role. This work aims to study the influence of five microorganisms isolated from drinking water biofilms on the survival and integration of both of these pathogens into biofilms. Results Firstly, both pathogens were studied for auto- and co-aggregation with the species isolated from drinking water; subsequently the formation of mono and dual-species biofilms by L. pneumophila or H. pylori with the same microorganisms was investigated. Neither auto- nor co-aggregation was observed between the microorganisms tested. For biofilm studies, sessile cells were quantified in terms of total cells by SYTO 9 staining, viable L. pneumophila or H. pylori cells were quantified using 16 S rRNA-specific peptide nucleic acid (PNA probes and cultivable cells by standard culture techniques. Acidovorax sp. and Sphingomonas sp. appeared to have an antagonistic effect on L. pneumophila cultivability but not on the viability (as assessed by rRNA content using the PNA probe, possibly leading to the formation of viable but noncultivable (VBNC cells, whereas Mycobacterium chelonae increased the cultivability of this pathogen. The results obtained for H. pylori showed that M. chelonae and Sphingomonas sp. help this pathogen to maintain cultivability for at least 24 hours. Conclusions It appears that M. chelonae may have an important role in the survival of both pathogens in drinking water. This work also suggests that the presence of some microorganisms can decrease the cultivability of L. pneumophila but not the viability which indicates that the presence of autochthonous microorganisms can lead to misleading results when the safety of water is assessed by cultivable methods alone.

Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

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Eitaro Aihara

2014-07-01

Full Text Available Helicobacter pylori (H. pylori is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1 significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB or chemotaxis (ΔcheY. ΔmotB (10(6 failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6 colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites

Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

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Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

2014-01-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases

Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster.

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Wang, Ming-yi; Shao, Chen; Li, Jie; Yang, Ya-Chao; Wang, Shao-bo; Hao, Jun-ling; Wu, Chun-mei; Gao, Xiao-zhong; Shao, Shi-he

2015-07-01

The duodenal ulcer promoting gene (dupA), located in the plasticity region of Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system (T4SS) with vir genes around dupA. In the study, we investigated the association between the dupA cluster status and the virulence of H. pylori in a littoral region of Northeast China. Two hundred and sixty-two H. pylori strains isolated from the chronic gastritis were examined to evaluate the dupA cluster status, cag PAI genes and vacA genotype using PCR and Western blot. Histopathologic evaluations of biopsy specimens were performed to analysis the association between the dupA cluster and the inflammatory response. IL-8 productions in gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured, respectively, to analysis the association between the dupA cluster status and IL-8 production. We found that gastric mucosal inflammatory cell infiltration was significantly higher in patients with dupA-positive H. pylori, including H. pylori with complete dupA cluster (2.71 ± 0.79) and incomplete dupA cluster (2.09 ± 0.61) than in patients with dupA-negative strain (1.73 ± 0.60, p dupA cluster. Gastric mucosal IL-8 levels were higher in the complete dupA cluster group than in other groups (p dupA cluster (1527.9 ± 180.0 pg/ml) than in those with an incomplete dupA cluster (1229.4 ± 75.3 pg/ml, p dupA negative (1201.9 ± 92.3 pg/ml, p dupA cluster in H. pylori is associated with inflammatory cell infiltration and IL-8 secretion, and H. pylori strain with a complete dupA cluster seems to be more virulent than other strains with the incomplete dupA cluster or dupA negative.

The association of dupA and Helicobacter pylori-related gastroduodenal diseases.

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Hussein, N R

2010-07-01

Helicobacter pylori is associated with the development of ulceration and gastric cancer. Recently, a novel virulence factor, duodenal ulcer promoting gene A (dupA), has been identified and found to associate with disease in some populations but not others. We investigated the relationship of dupA genotypes and H. pylori-related clinical outcomes by meta-analysis using previous reports of 2,358 patients from around the world. dupA-positive genotypes was found in 48% and was associated with duodenal ulcer (p = 0.001, odds ratio [OR] = 1.4, confidence interval [CI] = 1.1-1.7). The prevalence of dupA-positivity and its association with disease differed among the various regions around the world. In South America, the highest prevalence was recorded (Colombia and Brazil) and a significant relationship was found between dupA-negative strains and both gastric ulcer (GU) and gastric cancer (GC) (for GU, p = 0.001, OR = 0.2, CI = 0.1-0.4 and for GC, p = 0.001, OR = 0.3, CI = 0.2-0.6). In China, a significant correlation between dupA-positive strains and GU (p = 0.001, OR = 5.5, CI = 2.4-12.4) and GC (p = 0.009, OR = 2, Cl = 1.1-3.1) was found. To conclude, dupA promotes duodenal ulceration in some populations and GU and GC in others. This is typical of other virulence factors, such as cagA. Hence, it was concluded that the H. pylori virulence factor, dupA, is a true virulence factor.

Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.

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Yuki Ito

Full Text Available Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer, while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT, which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/- or wild-type mice, bacterial recovery significantly increased in Jα18(-/- compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/- compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

Comparative proteome analysis of Helicobacter pylori clinical strains by two-dimensional gel electrophoresis.

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Zhang, Ya-nan; Ding, Shi-gang; Huang, Liu-huan; Zhang, Jing; Shi, Yan-yan; Zhong, Li-jun

2011-10-01

To investigate the pathogenic properties of Helicobacter pylori by comparing the proteome map of H. pylori clinical strains. Two wild-type H. pylori strains, YN8 (isolated from biopsy tissue of a gastric cancer patient) and YN14 (isolated from biopsy tissue of a gastritis and duodenal ulcer patient), were used. Proteomic analysis, using a pH range of 3-10 and 5-8, was performed. The individual proteins were identified by quadrupole time-of-flight (Q-TOF) mass spectrometer and protein database search. Variation in spot patterns directed towards differential protein expression levels was observed between the strains. The gel revealed prominent proteins with several protein "families". The comparison of protein expressions of the two strains reveals a high variability. Differentially present or absent spots were observed. Nine differentially expressed protein spots identified by Q-TOF included adenosine triphosphate (ATP)-binding protein, disulfide oxidoreductase B (DsbB)-like protein, N utilization substance A (NusA), ATP-dependent protease binding subunit/heat shock protein, hydantoin utilization protein A, seryl-tRNA synthetase, molybdenum ABC transporter ModD, and hypothetical proteins. This study suggests that H. pylori strains express/repress protein variation, not only in terms of the virulence proteins, but also in terms of physiological proteins, when they infect a human host. The difference of protein expression levels between H. pylori strains isolated from gastric cancer and gastritis may be the initiator of inflammation, and result in the different clinical presentation. In this preliminary study, we report seven differential proteins between strains, with molecule weights from approximately 10 kDa to approximately 40 kDa. Further studies are needed to investigate those proteins and their function associated with H. pylori colonization and adaptation to host environment stress.

Aggressive root pathogen Phellinus noxius and implications for western Pacific Islands

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Sara M. Ashiglar; Phil G. Cannon; Ned B. Klopfenstein

2015-01-01

Phellinus noxius is an aggressive root rot pathogen affecting tropical and subtropical forests. Causing much damage in tropical Asia, Africa, Taiwan, Japan and the Pacific Islands, its wide host range encompasses more than 200 plant species representing 59 families (Ann et al. 2002). It can devastate agricultural plantations of tea, rubber, cocoa, avocados,...

(CAG)(n)-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition.

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Owen, Barbara A L; Yang, Zungyoon; Lai, Maoyi; Gajec, Maciej; Gajek, Maciez; Badger, John D; Hayes, Jeffrey J; Edelmann, Winfried; Kucherlapati, Raju; Wilson, Teresa M; McMurray, Cynthia T

2005-08-01

Cells have evolved sophisticated DNA repair systems to correct damaged DNA. However, the human DNA mismatch repair protein Msh2-Msh3 is involved in the process of trinucleotide (CNG) DNA expansion rather than repair. Using purified protein and synthetic DNA substrates, we show that Msh2-Msh3 binds to CAG-hairpin DNA, a prime candidate for an expansion intermediate. CAG-hairpin binding inhibits the ATPase activity of Msh2-Msh3 and alters both nucleotide (ADP and ATP) affinity and binding interfaces between protein and DNA. These changes in Msh2-Msh3 function depend on the presence of A.A mispaired bases in the stem of the hairpin and on the hairpin DNA structure per se. These studies identify critical functional defects in the Msh2-Msh3-CAG hairpin complex that could misdirect the DNA repair process.

Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

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Marina Kovalenko

Full Text Available The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111 with mice carrying a conditional (floxed Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.