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.

Prevalence of Helicobacter pylori cagA and vacA Genes and Their Correlation with Gastrointestinal Diseases

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 151-156
Author(s):  
Amr M. El-Sabbagh ◽  
Ahmed H. Yassen ◽  
Maha M abdelsalam
Keyword(s):  
Helicobacter Pylori ◽  
Gastrointestinal Diseases ◽  
Vital Role ◽  
Gastroduodenal Disease ◽  
Urease Test ◽  
Cytotoxin Associated Gene A ◽  
Gastrointestinal Illnesses ◽  
Clinical Illness ◽  
H Pylori ◽  
Variant Genes

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium, producing gastric ulcer, mild to severe gastritis, gastric carcinoma and lymphoma to the gastric mucosa-associated lymphoid tissue through many virulence influences. Among the virulence factors identified; vacuolating cytotoxin A (vacA) and cytotoxin-associated gene A (cagA) play an important role. Objective: In this study, we try to discover the relation between vacA variant and cagA genes with the clinical illness occurring in H. pylori patients Methodology: One hundred and forty patients were included in our study. Dual biopsy samples were taken from the stomach; one was examined by the urease test, and the other one was stored at −80°C for DNA extraction followed by PCR. The existence of H. pylori in the tissue was recognized by the existence of glmM gene and its detection by PCR. All the positive samples were additionally tested by PCR for the occurrence of cagA and vacA variant genes. Results: Our study demonstrated that cagA and vacA genes were found among 50% and 57% respectively of H. pylori patients complaining from gastrointestinal illnesses and that vacA s1/s2 was the main genotype found in H. pylori persons with gastroduodenal disease. Significant relation between vacA s1 gene and cagA gene was found. Conclusion: vacA s1 genotype has a vital role in upper gastrointestinal illnesses progress.

scholarly journals Mixed Infections ofHelicobacter pyloriIsolated from Patients with Gastrointestinal Diseases in Taiwan

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Chih-Ho Lai ◽  
Ju-Chun Huang ◽  
Chuan Chiang-Ni ◽  
Ju-Pi Li ◽  
Lii-Tzu Wu ◽  
...  
Keyword(s):  
Virulence Genes ◽  
Gastrointestinal Diseases ◽  
Mixed Infections ◽  
Hostile Environment ◽  
High Genetic Diversity ◽  
Vacuolating Cytotoxin ◽  
Severity Of Disease ◽  
Cytotoxin Associated Gene A ◽  
H Pylori ◽  
Upper Gastrointestinal

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

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 Helicobacter pylori Induces IL-33 Production and Recruits ST-2 to Lipid Rafts to Exacerbate Inflammation

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1290 ◽  
Author(s):  
Kuo ◽  
Chen ◽  
Lo ◽  
Feng ◽  
Wu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Lipid Rafts ◽  
Intracellular Signaling ◽  
Membrane Lipid ◽  
In Vivo Studies ◽  
Infected Cells ◽  
Membrane Bound ◽  
H Pylori ◽  
Receptor Accessory Protein

Helicobacter pylori colonizes human gastric epithelial cells and contributes to the development of several gastrointestinal disorders. Interleukin (IL)-33 is involved in various immune responses, with reported proinflammatory and anti-inflammatory effects, which may be associated with colitis and colitis-associated cancer. IL-33 induces the inflammatory cascade through its receptor, suppression of tumorigenicity-2 (ST-2). Binding of IL-33 to membrane-bound ST-2 (mST-2) recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates intracellular signaling pathways. However, whether IL-33/ST-2 is triggered by H. pylori infection and whether this interaction occurs in lipid rafts remain unclear. Our study showed that both IL-33 and ST-2 expression levels were significantly elevated in H. pylori-infected cells. Confocal microscopy showed that ST-2 mobilized into the membrane lipid rafts during infection. Depletion of membrane cholesterol dampened H. pylori-induced IL-33 and IL-8 production. Furthermore, in vivo studies revealed IL-33/ST-2 upregulation, and severe leukocyte infiltration was observed in gastric tissues infected with H. pylori. Together, these results demonstrate that ST-2 recruitment into the lipid rafts serves as a platform for IL-33-dependent H. pylori infection, which aggravates inflammation in the stomach.

scholarly journals What is the Relationship Between Helicobacter Pylori CagA Genotypes and Gastrointestinal Diseases in the Iranian Population? A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Masoud Keikha ◽  
Mohsen Karbalaei
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Meta Analysis ◽  
Gastrointestinal Diseases ◽  
Iranian Population ◽  
Cancer Disease ◽  
Gastrointestinal Complications ◽  
Cytotoxin Associated Gene A ◽  
H Pylori ◽  
The Relationship

Abstract Background: Helicobacter pylori (H. pylori) is one of the most well-known risk factors for getting the gastric cancer disease. In recent studies, the relationship between its virulence factors, specially CagA (cytotoxin‐associated gene A) toxin and development into the gastrointestinal diseases is taken into consideration. According to review of literature, despite the presence of four motifs A, B, C, and D in CagA toxin, two motifs C and D are more associated with gastrointestinal complications in patients who are infected by H. pylori. Methods: In the present study, we researched about theses ambiguities using a comprehensive meta-analysis study. In this study, we assessed the information of 1762 Iranian patients for potential relationship between all genotypes of cagA gene and gastrointestinal diseases.Results: According to statistical analysis, the abundance of cagA genotypes AB, ABC, ABCC, ABCCC, and ABD in Iranian population is 5.52%, 80.18%, 22.81%, 2.76%, and 0% respectively. In addition, it was determined that there is a significant relationship between cagA genotypes ABCC and ABCCC on the one hand and cagA genotype ABCCC on the other hand with susceptibility to chronic gastritis and gastric cancer respectively.Conclusions: Overall, it can be concluded that the higher number of EPIYA-C copy numbers lead to the higher risk of gastric cancer. According to our results, it seems that the presence of EPIYA-ABCCC motif in strains of H. pylori should be considered as an appropriate marker in preventing the gastric cancer among the Iranian population.

scholarly journals Statins’ Regulation of the Virulence Factors of Helicobacter pylori and the Production of ROS May Inhibit the Development of Gastric Cancer

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1293
Author(s):  
Ting-Yu Lin ◽  
Wen-Hsi Lan ◽  
Ya-Fang Chiu ◽  
Chun-Lung Feng ◽  
Cheng-Hsun Chiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Virulence Factors ◽  
Treatment Strategies ◽  
Vacuolating Cytotoxin ◽  
Cholesterol Levels ◽  
Cytotoxin Associated Gene A ◽  
H Pylori ◽  
Cellular Components ◽  
Development Of Gastric Cancer

Conventionally, statins are used to treat high cholesterol levels. They exhibit pleiotropic effects, such as the prevention of cardiovascular disease and decreased cancer mortality. Gastric cancer (GC) is one of the most common cancers, ranking as the third leading global cause of cancer-related deaths, and is mainly attributed to chronic Helicobacter pylori infection. During their co-evolution with hosts, H. pylori has developed the ability to use the cellular components of the host to evade the immune system and multiply in intracellular niches. Certain H. pylori virulence factors, including cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and cholesterol-α-glucosyltransferase (CGT), have been shown to exploit host cholesterol during pathogenesis. Therefore, using statins to antagonize cholesterol synthesis might prove to be an ideal strategy for reducing the occurrence of H. pylori-related GC. This review discusses the current understanding of the interplay of H. pylori virulence factors with cholesterol and reactive oxygen species (ROS) production, which may prove to be novel therapeutic targets for the development of effective treatment strategies against H. pylori-associated GC. We also summarize the findings of several clinical studies on the association between statin therapy and the development of GC, especially in terms of cancer risk and mortality.

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 Simple and Accurate PCR-Based System for Typing Vacuolating Cytotoxin Alleles of Helicobacter pylori

1999 ◽  
Vol 37 (9) ◽  
pp. 2979-2982 ◽  
Author(s):  
J. C. Atherton ◽  
T. L. Cover ◽  
R. J. Twells ◽  
M. R. Morales ◽  
C. J. Hawkey ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
South America ◽  
Sequence Data ◽  
Signal Sequence ◽  
The United States ◽  
Nucleotide Sequence Analysis ◽  
Vacuolating Cytotoxin ◽  
Cytotoxin Associated Gene A ◽  
Primer Annealing ◽  
H Pylori

Alleles of the vacuolating cytotoxin gene (vacA) ofHelicobacter pylori vary between strains, particularly in the region encoding the signal sequence (which may be type s1 or s2) and the midregion (which may be type m1 or m2). Using a PCR-based typing system developed in the United States, we showed that 36 strains from Asia and South America were all vacA signal sequence type s1; 3 were midregion type m1 and 11 were m2, but 22 could not be typed for the vacA midregion. All strains possessedcagA (cytotoxin-associated gene A), another virulence marker. vacA nucleotide sequence analysis showed that midregion typing failure was due to base substitutions at the primer annealing sites. Using the new sequence data, we developed two new PCR-based vacA midregion typing systems, both of which correctly typed 41 U.S. strains previously typed by the old system and successfully typed all 36 of the non-U.S. strains. All previously untypeable strains were vacA m1, other than one m1/m2 hybrid. In summary, we describe and validate a simple PCR-based system for typing vacuolating cytotoxin (vacA) alleles of H. pylori and show that this system correctly identifies the signal and midregion types of vacA in 77 strains from Asia and North and South America.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Genotyping pattern of the vacuolating cytotoxin A and cytotoxin associated gene A of the Helicobacter pylori strains detected in fecal samples of household dogs

2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Asieh Bolandi ◽  
Saam Torkan ◽  
Iman Alavi
Keyword(s):  
Helicobacter Pylori ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Pcr Amplification ◽  
Rrna Gene ◽  
Fecal Samples ◽  
The Status ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

In despite of the high clinical impact of Helicobacter pylori, its exact sources and routes of transmission are unknown. Dogs may play an imperative role in the transmission of H. pylori to humans. The current investigation was done to study the status of vacA and cagA genotypes in the H. pylori strains of dogs. One-hundred and fifty fecal samples were collected from healthy and complicated household dogs. Genomic DNA was extracted from fecal samples and presence of 16S rRNA gene was studied using the PCR amplification. Distribution of vacA and cagA genotypes were studied by the multiplex PCR. Thirteen out of 150 fecal samples (8.66%) were positive for H. pylori 16S rRNA gene. Prevalence of H. pylori in healthy and complicated dogs were 5.55% and 8.57%, respectively. Male had the higher prevalence of H. pylori (P=0.038). The most commonly detected genotypes among the H. pylori strains were vacAs1A (61.53%), cagA (38.46%), vacAm1a (38.46%), vacAs2 (30.76%) and vacAm2 (30.76%). The most commonly detected combined genotypes were s1aCagA (30.76%), s1am1a (23.07%), s2m1a (23.07%) and s2CagA (23.07%). Iranian household dogs harbor H. pylori in their fecal samples similar in genotypes of the vacA and cagA alleles which suggest that complicated and even healthy dogs may be the latent host of the H. pylori and its genotypes. However, supplementary studies are required to found the exact role of dogs as a definitive host of the H. pylori.

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