scholarly journals High prevalence of cytotoxin positive Helicobacter pylori in patients unrelated to the presence of peptic ulcers in Japan

Gut ◽  
1997 ◽  
Vol 41 (4) ◽  
pp. 463-468 ◽  
Author(s):  
K Ogura ◽  
F Kanai ◽  
S Maeda ◽  
H Yoshida ◽  
M Ogura ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Western Blot ◽  
Gastrointestinal Diseases ◽  
Normal Mucosa ◽  
Peptic Ulcers ◽  
Western Blot Assay ◽  
Vacuolating Cytotoxin ◽  
Western Blot Method ◽  
High Prevalence ◽  
H Pylori

Background—It has been reported that infection with vacuolating cytotoxin positive Helicobacter pyloristrains is associated with gastroduodenal disease in Western countries.Aims—To evaluate the prevalence of cytotoxin producing strains among patients with H pyloriinfection in relation to gastrointestinal diseases in Japan.Patients—Ninety seven patients undergoing endoscopy.Methods—A Western blot assay was conducted to detect serum antibodies against the cytotoxin using recombinant cytotoxin (VacA protein) as an antigen. To obtain a purified recombinant cytotoxin, the vacA gene (2233 nucleotides) was cloned into an expression vector to produce the protein (744 amino acids), which was expressed in Escherichia coli.Results—Serum IgG antibodies to the cytotoxin were present in 85%, 95%, 95%, and 100% of infected patients with gastric ulcer (n=26), duodenal ulcer (n=21), chronic gastritis (n=19), and endoscopically normal mucosa (n=14), respectively.Conclusion—The western blot method using recombinant VacA protein is simple and useful for detecting antibody to vacuolating cytotoxin. This method showed antibodies against cytotoxin were highly prevalent, even in subjects with endoscopically normal mucosa in Japan, indicating that the cytotoxin may not be an independent cause of gastrointestinal diseases induced by H pylori infection.

scholarly journals Structural basis for the peptidoglycan recognition by Helicobacter pylori Csd4

2014 ◽  
Vol 70 (a1) ◽  
pp. C817-C817
Author(s):  
Hyoun Sook Kim ◽  
Byung Woo Han ◽  
Byung Il Lee ◽  
Se Won Suh
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Cell Shape ◽  
Gastrointestinal Diseases ◽  
Structural Basis ◽  
Free Form ◽  
Peptic Ulcers ◽  
Carboxypeptidase H ◽  
Ligand Free ◽  
H Pylori

Helicobacter pylori infection causes a variety of gastrointestinal diseases including peptic ulcers and gastric cancer. The colonization of this bacterium in the gastric mucosa is required for the survival in the stomach. Its colonization of the gastric mucosa of human stomach depends on its motility, which is facilitated by the helical cell shape. In H. pylori, crosslinking relaxation or trimming of peptidoglycan muropeptide affects the helical shape. Among several cell shape-determining peptidoglycan hydrolases identified in H. pylori, Csd4 is a Zn2+-dependent D,L-carboxypeptidase that cleaves the bond between the γ-D-Glu and mDAP bond of the uncrosslinked tripeptide of peptidoglycan (L-Ala-γ-D-Glu-mDAP) to produce L-Ala-γ-D-Glu dipeptide and mDAP, promoting the helical cell shape. Inhibition of D,L-carboxypeptidase activity of Csd4 may represent a novel therapeutic approach. We report here the crystal structures of H. pylori Csd4 in three different states: the ligand-free form, the substrate-bound form, and the product-bound form. H. pylori Csd4 consists of three domains: an N-terminal D,L-carboxypeptidase domain, a novel β-barrel domain, and a C-terminal immunoglobulin-like domain. Our ligand-bound structures provide structural basis of peptidoglycan recognition by D,L-carboxypeptidase. H. pylori Csd4 recognizes primarily the terminal mDAP of the tripeptide substrate and undergoes a significant structural change upon binding either mDAP or mDAP-containing tripeptide.

scholarly journals Prevalence of Helicobacter pylori vacA, cagA, cagE1, cagE2, dupA and oipA Genotypes in Patients With Gastrointestinal Diseases

2020 ◽  
Author(s):  
Hossein Masoumi Asl ◽  
Ali Badamchi ◽  
Shima Javadinia ◽  
Siamak Khaleghi ◽  
Leila Tehraninia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastrointestinal Diseases ◽  
Cancer Group ◽  
Urease Test ◽  
High Prevalence ◽  
Vaca Gene ◽  
H Pylori ◽  
Positive Results ◽  
Gastroenterology Unit

Helicobacter pylori (H. pylori) is a bacterium that resides in the human stomach, which is associated with gastroduodenal diseases. We investigate the prevalence of cagA, vacA, oipA, cagE1, cagE2 and dupA genotypes in H. pylori isolated from patients with Gastric ulcer, duodenal ulcer, and Gastric Cancer. Collected 74 samples from the Gastroenterology Unit of the Rasool Akram Hospital were included in this study. Gastric disorders were identified by endoscopy .gastric cancer was further confirmed by histopathology. H. pylori were detected by the urease test. Subsequently, DNA was extracted from gastric tissue of the subjects with the CLO-test yielded positive results. In general, 74 patients with a mean age of 53.45 years (Range 22 to 86-year-old), including 45 men and 29 women, were studied. Among 74 H. pylori-positive patients, 70 (94.5%) patients were positive for the cagA gene. About 95.8% (23/24) of the patients with gastric carcinoma were dupA positive and VacA gene (91.8%). The oipA genotype was detected in 71 (96%) of H.pylori positive samples. This gene was more common in patients with gastritis rather than cancer group. Also, 97.2% of 74 H. pylori isolates were cagE2-positive. In 25 patients with PUD, the occurrence percent of cagA+/VacA+, cagA+/Vac- , cagA- /VacA+ and cagA- /VaxA- genotypes were found 80%, 12%, 4.2% and 4.2 respectively. The results of the present study suggest that a high prevalence of virulent factors could contribute to the risk of developing gastroduodenal diseases.

scholarly journals Helicobacter pyloriin First Nations and Recent Immigrant Populations in Canada

2012 ◽  
Vol 26 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Nicola L Jones ◽  
Naoki Chiba ◽  
Carlo Fallone ◽  
Alan Thomson ◽  
Richard Hunt ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
First Nations ◽  
Cost Effective ◽  
Gastrointestinal Diseases ◽  
Population Based ◽  
Peptic Ulcers ◽  
Canadian Population ◽  
High Prevalence ◽  
H Pylori ◽  
Low Prevalence

The diminishing prevalence ofHelicobacter pyloriinfection among most segments of the Canadian population has led to changes in the etiologies and patterns of associated upper gastrointestinal diseases, including fewer peptic ulcers and their complications. Canadian Aboriginals and recent immigrants are among populations in which the prevalence ofH pyloriinfection remains high and, therefore, the health risks imposed byH pyloriremain a significant concern. Population-based strategies forH pylorieradication in groups with a low prevalence of infection are unlikely to be cost effective, but such measures are attractive in groups in which the prevalence rates of infection remain substantial. In addition to a lower prevalence of peptic ulcers and dyspepsia, the public health value of eradication may be particularly important if this leads to a reduction in the prevalence of gastric cancer in high prevalence groups. Therefore The Canadian Helicobacter Study Group held a conference that brought together experts in the field to address these issues, the results of which are reviewed in the present article. Canadians with the highest prevalence ofH pyloriinfection are an appropriate focus for considering the health advantages of eradicating persistent infection. In Canadian communities with a high prevalence of bothH pyloriand gastric cancer, there remains an opportunity to test the hypothesis thatH pyloriinfection is a treatable risk factor for malignancy.

scholarly journals Pathogenesis of Helicobacter pylori Infection

2006 ◽  
Vol 19 (3) ◽  
pp. 449-490 ◽  
Author(s):  
Johannes G. Kusters ◽  
Arnoud H. M. van Vliet ◽  
Ernst J. Kuipers
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Clinical Symptoms ◽  
Gastrointestinal Diseases ◽  
Immune Gene ◽  
Human Pathogens ◽  
Vacuolating Cytotoxin ◽  
Chronic Active Gastritis ◽  
Key Factor ◽  
H Pylori

SUMMARY Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.

scholarly journals Diversity of Helicobacter pylori vacA andcagA Genes and Relationship to VacA and CagA Protein Expression, Cytotoxin Production, and Associated Diseases

1998 ◽  
Vol 36 (4) ◽  
pp. 944-948 ◽  
Author(s):  
Jochen Rudi ◽  
Christof Kolb ◽  
Matthias Maiwald ◽  
Dirk Kuck ◽  
Andreas Sieg ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Signal Sequence ◽  
Peptic Ulcers ◽  
Virulence Determinants ◽  
Middle Region ◽  
Vacuolating Cytotoxin ◽  
Ulcer Disease ◽  
H Pylori

The vacuolating cytotoxin and the cytotoxin-associated protein, encoded by vacA and cagA, respectively, are important virulence determinants of Helicobacter pylori. Sixty-five H. pylori strains were isolated from dyspeptic patients (19 with peptic ulcer disease, 43 with chronic gastritis, and 3 with gastric cancer) and studied for differences in thevacA and cagA genes and their relationship to VacA and CagA expression, cytotoxin activity, and the clinical outcome of infection. By PCR, fifty-four (83.1%) of 65 strains had thevacA signal sequence genotype s1 and only 10 (15.4%) had the type s2. After primer modification, the vacAmiddle-region types m1 and m2 were detected in 24 (36.9%) and 41 (63.1%) strains, respectively. The combinations s1-m2 (31 [47.7%]) and s1-m1 (23 [35.4%]) occurred more frequently than s2-m2 (10 [15.4%]) (P = 0.01). No strain with the combination s2-m1 was found. All 19 patients with peptic ulcers harbored type s1 strains, in contrast to 32 (74.4%) of 43 patients with gastritis (P = 0.02). The vacA genotype s1 was associated with the presence of cagA (P < 0.0001), VacA expression (P < 0.0001), and cytotoxin activity (P = 0.003). The cagA gene was detectable in 48 (73.8%) of 65 isolates and present in 16 (84.2%) of 19 ulcer patients and 29 (67.4%) of 43 patients with gastritis (P = 0.17). The vacA genotypes of GermanH. pylori isolates are identical to those previously reported. H. pylori strains of vacA type s1 are associated with the occurrence of peptic ulceration and the presence ofcagA, cytotoxin activity, and VacA expression.

scholarly journals Western Blot Method Evaluation for Detection of Helicobacter pylori Infections against H. pylori Ag in Stool Enzyme-Linked Immunoassay in Adult Egyptian Patients

2016 ◽  
Vol 4 (3) ◽  
pp. 352-358
Author(s):  
Mohamed E. Rashed ◽  
Amer M.M. ◽  
Mostafa Elnakeeb ◽  
Waleed Saeed Omer
Keyword(s):  
Helicobacter Pylori ◽  
Western Blot ◽  
Virulence Factors ◽  
Diagnostic Value ◽  
Type I ◽  
Western Blot Method ◽  
Egyptian Patients ◽  
Cytotoxin Associated Gene A ◽  
H Pylori ◽  
Medical Burden

Helicobacter pylori infection is tremendous medical burden especially in developing countries. Various immunological tests are available for diagnosis of H. pylori infection. Western blot method is proven to be promising for Precise, easy reading, sensitive and specific detection of H. pylori infections, besides it also permits the detection for the different virulence factors of CagA / VacA positive strains (type I). The objective of this study is to evaluate the diagnostic value of commercial Western Blot (WB) method in the serological diagnosis of H. pylori infections against the H. pylori Ag in stool (HpSAg) using commercial enzyme-linked immunoassay (ELISA) in adult dyspeptic Egyptian patients. Also we investigated the prevalence of virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) in the infected patients. Samples from 46 adult dyspeptic Egyptian patients were tested by the two methods. WB test gave accurate confirmed result with (82.6% accuracy and 89.5% sensitivity) compared to HpSAg test. Also the results indicated a high seroprevalence of cagA- and vacA-positive virulent H. pylori type I strains in adult infected population indicate that such strains may be common in this population and responsible for the majority of H. pylori infection among adult Egyptians. We concluded that WB method could be useful for the confirmatory detection of antibody profiles to H. pylori antigens and virulence factors in adult Egyptian patients.Int J Appl Sci Biotechnol, Vol 4(3): 352-358

scholarly journals Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jia-Yin Yeh ◽  
Hwai-Jeng Lin ◽  
Chia-Jung Kuo ◽  
Chun-Lung Feng ◽  
Chia-Huei Chou ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Lipid Rafts ◽  
Campylobacter Jejuni ◽  
Nuclear Factor Kappa B ◽  
Gastrointestinal Diseases ◽  
Membrane Lipid ◽  
Cytolethal Distending Toxin ◽  
Vacuolating Cytotoxin ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.

scholarly journals Cost-effectiveness Analysis Comparing Vonoprazanbased Triple Therapy with Proton Pump Inhibitorbased Therapy in the Treatment of Helicobacter pylori Infection in Thailand

2021 ◽  
Vol 73 (12) ◽  
pp. 823-831
Author(s):  
Jadesada Lertsirimunkong ◽  
Wiwat Thavornwattanayong ◽  
Yosita Napuk ◽  
Watcharapong Ajcharoen ◽  
Vipavee Chaisitsanguan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Cost Effectiveness ◽  
Triple Therapy ◽  
Gastrointestinal Diseases ◽  
Dominant Strategy ◽  
Peptic Ulcers ◽  
Life Years ◽  
First Choice ◽  
H Pylori ◽  
The Cost

Objective: Helicobacter pylori (H. pylori) infection is one of the leading causes of gastrointestinal diseases such as dyspepsia, peptic ulcers. Thailand has a 45.9% prevalence of the infection and an increasing rate of resistance to clarithromycin, leading to standard treatments being less successful. Vonoprazan represents a novel drug offering a new treatment regimen. Although vonoprazan has been available in Thailand since 2019, its cost-effectiveness has not been studied previously.Materials and Methods: This study analysed the cost-effectiveness of vonoprazan-based triple therapy compared with PPI-based therapy, in treating clarithromycin resistant H. pylori, by using the markov model from a societal perspective.Results: The total cost of vonoprazan-based triple therapy, levofloxacin-PPI based triple therapy and concomitant-PPI therapy were 784,932.08 baht, 783,863.65 baht and 783,874.55 baht respectively. The quality-adjusted life years (QALYs) of vonoprazan-based triple therapy, levofloxacin-PPI based triple therapy and concomitant-PPI therapy were 25.1118 years, 25.1147 years and 25.1054 years respectively. The cost-effectiveness ratio (CER) of vonoprazanbased triple therapy, levofloxacin-PPI based triple therapy and concomitant-PPI therapy were 31,257.50 baht/ QALYs, 31,211.35 baht/QALYs and 31,223.34 baht per QALYs respectively.Conclusion: Therefore, levofloxacin-PPI based triple therapy was found to be the most cost-effective regimen and the dominant strategy compared with concomitant-PPI or vonoprazan-based triple therapy. It provided higher QALYs and lower treatment costs. Levofloxacin-PPI based triple therapy should be the first choice of an alternative strategy in treating clarithromycin-resistant H. pylori. The results of this study can be used by policymakers to help inform their decisions.

scholarly journals Major virulence factors, VacA and CagA, are commonly positive inHelicobacter pylori isolates in Japan

Gut ◽  
1998 ◽  
Vol 42 (3) ◽  
pp. 338-343 ◽  
Author(s):  
S Maeda ◽  
K Ogura ◽  
H Yoshida ◽  
F Kanai ◽  
T Ikenoue ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factors ◽  
Japanese Patients ◽  
Type I ◽  
Activity Type ◽  
Vacuolating Cytotoxin ◽  
Specific Antibodies ◽  
High Prevalence ◽  
H Pylori ◽  
Very High

Background—VacA and CagA proteins have been reported to be major virulence factors of Helicobacter pylori. However, antibodies against these proteins are frequently found in the sera of Japanese patients regardless of their gastroduodenal status.Aim—To evaluate the expression of VacA and CagA proteins by H pylori strains isolated in Japan.Methods—By using specific antibodies raised against recombinant VacA and CagA proteins, the expression of VacA and CagA was evaluated in 68 H pylori strains isolated from Japanese patients; a vacuolating assay and genotyping of thevacA gene were also used in the evaluation. The results were analysed in relation to the gastroduodenal diseases of the hosts.Results—VacA and CagA proteins were expressed in 59/68 (87%) and in 61/68 (90%) isolates respectively. The vacuolating assay was positive in 57/68 (84%) isolates, indicating that most immunologically VacA positive strains produced active cytotoxin. The prevalence of infection with strains expressing CagA and positive for vacuolating activity (Type I) was very high, 54/68 (79%), irrespective of the gastroduodenal status of the host.Conclusion—Most H pylori isolates in Japan are positive for vacuolating cytotoxin and CagA, and thus these virulence factors cannot be used as markers to discern the risk of developing serious gastroduodenal pathologies in the hosts. However, the high prevalence of infection with strains positive for vacuolating cytotoxin and CagA may contribute to the characteristics of H pylori infection in Japan.

scholarly journals Effects of Infections of Helicobacter Pylori With Different Virulent Factors on Severity of Gastrointestinal Diseases

2021 ◽  
Author(s):  
Yan Zhang ◽  
Xiang-ming Fang ◽  
Kui Tian
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Infections ◽  
Gastrointestinal Diseases ◽  
Ulcer Bleeding ◽  
Type I ◽  
Peptic Ulcers ◽  
Type Ii ◽  
Type Iii ◽  
Significant Difference ◽  
H Pylori

Abstract Background: Helicobacter Pylori (H. pylori) infection, one of the most common chronic bacterial infections, has been considered as a major cause of diseases such as lymphoma, gastritis, peptic ulcers, and stomach cancer. Here, we aimed to determine whether H. pylori strains with different virulence contribute to the gastrointestinal diseases differentially in clinical settings, which may provide future direction for eradication of H. pylori infection. Methods: We recruited 501 patients with gastrointestinal disorders for analysis of antibody types of H. pylori infection. Correlation analysis was done to determine the association of different virulence of H. pylori with patients’ baseline parameters and personal disease history. Next, subjects with each type of anti- H. pylori infection antibody were subjected to esophagogastro duodenoscopy（EGD) and colonoscopy examinations. The pathological diagnosis was also conducted in endoscopic samples. Chi-squared test was employed to compare the differences in endoscopic assessments and pathological findings among three types of H. pylori infection determined by the presence of antibodies to virulent factors. Results: There were 296 cases with Type I H. pylori infection, 120 cases with Type II H. pylori infection, and 85 cases without H. pylori infection (negative, Type III). No correlation was found between different virulence of H. pylori and participants’ baseline data (P > 0.05). EGD results showed that the incidences of peptic ulcer, bleeding and malignant lesions in Type I group were significantly higher than that in Type II and Type III (P＜0.05). Despite of increased trends of incidences of precancerous alterations and the malignance in Type I group compared with type II and III groups, there was no significant difference (P > 0.05). In addition, coloscopic features were similar among three groups. On the other hand, infections of H. pylori with cytotoxin-associated gene A (CagA) and/or vacuolating cytotoxin A (VacA) virulent factors resulted in more severe histopathological diseases than that with only Ure A/B factor and without infection (P < 0.05). Conclusions: Infections of H. pylori strains with CagA/VacA are likely to cause development of severe gastrointestinal diseases. These results are helpful to treat for H. pylori infection clinically.

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