scholarly journals Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 27
Author(s):  
Jacek Baj ◽  
Alicja Forma ◽  
Monika Sitarz ◽  
Piero Portincasa ◽  
Gabriella Garruti ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Virulence Factors ◽  
Premalignant Lesions ◽  
Bacterial Pathogenicity ◽  
Current State ◽  
Genetic And Environmental Factors ◽  
H Pylori ◽  
Stimulation Of

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

scholarly journals The Prevalence ofHelicobacter pyloriVirulence Factors in Bhutan, Vietnam, and Myanmar Is Related to Gastric Cancer Incidence

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Tran Thi Huyen Trang ◽  
Seiji Shiota ◽  
Miyuki Matsuda ◽  
Tran Thanh Binh ◽  
Rumiko Suzuki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Virulence Factors ◽  
Cancer Incidence ◽  
The Status ◽  
The Difference ◽  
H Pylori ◽  
Significant Health ◽  
Development Of Gastric Cancer

Gastric cancer is a significant health problem in Asia. Although the prevalence ofHelicobacter pyloriinfection is similar in Bhutan, Vietnam, and Myanmar, the incidence of gastric cancer is highest in Bhutan, followed by Vietnam and Myanmar. We hypothesized thatH. pylorivirulence factors contribute to the differences. The status ofcagA,vacA,jhp0562, andβ-(1,3)galT(jhp0563)was examined in 371H. 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 forcagA,vacAs1,vacAm1, andjhp0562-positive/β-(1,3)galT-negative was significantly higher in Bhutan than in Vietnam and Myanmar and correlated with gastric cancer incidence. Moreover, gastritis-staging scores measured by histology of gastric mucosa were significantly higher in quadruple-positive strains. We suggest that thecagA,vacAs1,vacAm1, andjhp0562-positive/β-(1,3)galT-negative genotype may play a role in the development of gastric cancer.

scholarly journals The role of the gastric bacterial microbiome in gastric cancer: Helicobacter pylori and beyond

2019 ◽  
Vol 12 ◽  
pp. 175628481989406 ◽  
Author(s):  
Christian Schulz ◽  
Kerstin Schütte ◽  
Julia Mayerle ◽  
Peter Malfertheiner
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Bacterial Pathogen ◽  
Gastric Carcinogenesis ◽  
Nucleotide Sequencing ◽  
Wide Field ◽  
Current State ◽  
Organ Systems ◽  
Bacterial Microbiome ◽  
H Pylori

A link between chronic inflammation and carcinogenesis has been depicted in many organ systems. Helicobacter pylori is the most prevalent bacterial pathogen, induces chronic gastritis and is associated with more than 90% of cases of gastric cancer (GC). However, the introduction of nucleotide sequencing techniques and the development of biocomputional tools have surpassed traditional culturing techniques and opened a wide field for studying the mucosal and luminal composition of the bacterial gastric microbiota beyond H. pylori. In studies applying animal models, a potential role in gastric carcinogenesis for additional bacteria besides H. pylori has been demonstrated. At different steps of gastric carcinogenesis, changes in bacterial communities occur. Whether these microbial changes are a driver of malignant disease or a consequence of the histologic progression along the precancerous cascade, is not clear at present. It is hypothesized that atrophy, as a consequence of chronic gastric inflammation, alters the gastric niche for commensals that might further urge the development of H. pylori-induced GC. Here, we review the current state of knowledge on gastric bacteria other than H. pylori and on their synergism with H. pylori in gastric carcinogenesis.

scholarly journals Relationship of Anti-Lewis x and Anti-Lewis y Antibodies in Serum Samples from Gastric Cancer and Chronic Gastritis Patients toHelicobacter pylori-Mediated Autoimmunity

2001 ◽  
Vol 69 (8) ◽  
pp. 4774-4781 ◽  
Author(s):  
Michael A. Heneghan ◽  
Ciaran F. McCarthy ◽  
Daiva Janulaityte ◽  
Anthony P. Moran
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Antibody Production ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Lewis Y ◽  
H Pylori ◽  
Negative Controls ◽  
Relationship Of

ABSTRACT Lewis (Le) antigens have been implicated in the pathogenesis of atrophic gastritis and gastric cancer in the setting ofHelicobacter pylori infection, and H. pylori-induced anti-Le antibodies have been described that cross-react with the gastric mucosa of both mice and humans. The aim of this study was to examine the presence of anti-Le antibodies in patients with H. pylori infection and gastric cancer and to examine the relationships between anti-Le antibody production, bacterial Le expression, gastric histopathology, and host Le erythrocyte phenotype. Anti-Le antibody production and H. pylori Le expression were determined by enzyme-linked immunosorbent assay, erythrocyte Le phenotype was examined by agglutination assays, and histology was scored blindly. Significant levels of anti-Lex antibody (P < 0.0001, T = 76.4, DF = 5) and anti-Ley antibody (P < 0.0001, T = 73.05, DF = 5) were found in the sera of patients with gastric cancer and other H. pylori-associated pathology compared with H. pylori-negative controls. Following incubation of patient sera with synthetic Le glycoconjugates, anti-Lex and -Ley autoantibody binding was abolished. The degree of the anti-Lex and -Leyantibody response was unrelated to the host Le phenotype but was significantly associated with the bacterial expression of Lex (r = 0.863,r 2 = 0.745, P < 0.0001) and Ley (r = 0.796,r 2 = 0.634, P < 0.0001), respectively. Collectively, these data suggest that anti-Le antibodies are present in most patients with H. pyloriinfection, including those with gastric cancer, that variability exists in the strength of the anti-Le response, and that this response is independent of the host Le phenotype but related to the bacterial Le phenotype.

scholarly journals Role of Interleukin-32 in Helicobacter pylori-Induced Gastric Inflammation

2012 ◽  
Vol 80 (11) ◽  
pp. 3795-3803 ◽  
Author(s):  
Kosuke Sakitani ◽  
Yoshihiro Hirata ◽  
Yoku Hayakawa ◽  
Takako Serizawa ◽  
Wachiko Nakata ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Cell Lines ◽  
Inflammatory Diseases ◽  
Nuclear Factor Κb ◽  
Gastric Disease ◽  
Ags Cells ◽  
Content Type ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection is associated with gastritis and gastric cancer. AnH. pylorivirulence factor, thecagpathogenicity island (PAI), is related to host cell cytokine induction and gastric inflammation. Since elucidation of the mechanisms of inflammation is important for therapy, the associations between cytokines and inflammatory diseases have been investigated vigorously. Levels of interleukin-32 (IL-32), a recently described inflammatory cytokine, are increased in various inflammatory diseases, such as rheumatoid arthritis and Crohn's disease, and in malignancies, including gastric cancer. In this report, we examined IL-32 expression in human gastric disease. We also investigated the function of IL-32 in activation of the inflammatory cytokines in gastritis. IL-32 expression paralleled human gastric tissue pathology, with low IL-32 expression inH. pylori-uninfected gastric mucosa and higher expression levels in gastritis and gastric cancer tissues.H. pyloriinfection increased IL-32 expression in human gastric epithelial cell lines.H. pylori-induced IL-32 expression was dependent on the bacterialcagPAI genes and on activation of nuclear factor κB (NF-κB). IL-32 expression induced byH. pyloriwas not detected in the supernatant of AGS cells but was found in the cytosol. Expression of theH. pylori-induced cytokines CXCL1, CXCL2, and IL-8 was decreased in IL-32-knockdown AGS cell lines compared to a control AGS cell line. We also found that NF-κB activation was decreased inH. pylori-infected IL-32-knockdown cells. These results suggest that IL-32 has important functions in the regulation of cytokine expression inH. pylori-infected gastric mucosa.

scholarly journals Effect of Helicobacter pylori Eradication on Epigenetic Changes in Gastric Cancer-related Genes

2021 ◽  
Vol 21 (4) ◽  
pp. 256-266
Author(s):  
Ji Min Choi ◽  
Sang Gyun Kim
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Gastric Carcinogenesis ◽  
Point Of View ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Helicobacter Pylori Eradication ◽  
Gastric Cancer Prevention ◽  
H Pylori

It is known that gastric carcinogenesis results from the progressive changes from chronic gastritis to gastric atrophy, intestinal metaplasia, dysplasia, and invasive carcinoma. Several genetic and epigenetic alterations are involved in this process, and Helicobacter pylori (H. pylori) infection is believed to induce the initiation and progression of these steps. From an epigenetic point of view, H. pylori induces hypermethylation of genes involved in the development of gastric cancer and regulates the expression of various microRNAs (miRNAs). These H. pylori-related epigenetic changes are accumulated not only at the site of neoplasm but also in the adjacent non-cancerous gastric mucosa. Thereby, a state vulnerable to gastric cancer known as an epigenetic field defect is formed. H. pylori eradication can have an effective chemopreventive effect in gastric carcinogenesis. However, the molecular biological changes that occur in the stomach environment during H. pylori eradication have not yet been established. Several studies have reported that H. pylori eradication can restore infection-related changes, especially epigenetic alterations in gastric cancer-related genes, but some studies have shown otherwise. Simply put, it appears that the recovery of methylated gastric cancer-related genes and miRNAs during H. pylori eradication may vary among genes and may also differ depending on the histological subtype of the gastric mucosa. In this review, we will discuss the potential mechanism of gastric cancer prevention by H. pylori eradication, mainly from an epigenetic perspective.

Intrafamilial Infection of Helicobacter Pylori: Abnormal Gastric Epithelial Cells, Pedestal-Rich H. Pylori Adherence, and a Gene Mutation in a Child with Protein-Losing Gastroenteropathy

2019 ◽  
Vol 2 (3) ◽  
pp. 83-99
Author(s):  
T.W. Wan ◽  
O. Khokhlova ◽  
W. Higuchi ◽  
I. Protasova ◽  
Olga V. Peryanova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Gene Mutation ◽  
Virulence Factor ◽  
East Asian ◽  
Gastric Epithelium ◽  
Gastric Epithelial Cells ◽  
H Pylori

Abstract Helicobacter pylori, one of the most prevalent human pathogens, colonizes the gastric mucosa and is associated with gastric diseases, such as gastritis and peptic ulcers, and is also a bacterial risk factor for gastric cancer. Cytotoxin-associated gene A (CagA) protein, a major virulence factor of H. pylori, is phosphorylated in cells at its Glu-Pro-IIe-Tyr-Ala (EPIYA) motif and is considered to trigger gastric cancer. CagA is classified into two forms, Western CagA with EPIYA-ABC and East Asian CagA with EPIYA-ABD, with the latter associated with a high risk of developing gastric cancer. CagA causes morphological transformation of cells, yielding the “hummingbird” phenotype in AGS cells and possibly membranous pedestals in the gastric epithelium, albeit rarely. H. pylori adherence to the gastric mucosa is not yet fully understood. Here, we describe an intrafamilial infection case of H. pylori, focusing on the gastric epithelium, H. pylori adherence, and a gene mutation in a child with protein-losing gastroenteropathy (characterized by excessive loss of plasma proteins into the gastrointestinal tract). H. pylori, which also infected family members (mother and father), was genetically a single clone with the virulence genes of an East Asian type. The patient’ gastric mucosa exhibited some unique features. Endoscopy revealed the presence of protein plugs on the mucosal surface, which were immunoelectrophoretically similar to serum proteins. Electron microscopy revealed abnormal gastric epithelial cells, totally covered with the secretions or possessing small swollen structures and irregular microvilli. The patient’s H. pylori infection was characterized by frequently occurring thick pedestals, formed along adherent H. pylori. The serum protein level returned to normal and the protein plugs disappeared after the successful eradication of H. pylori, albeit with lag periods for healing. He had a mutation in the OCRL1 gene, associated with Dent disease (asymptomatic proteinuria). Thus, in the patient’s gastric mucosa, we found the abnormal gastric epithelial cells, which may be caused by an OCRL1 mutation or H. pylori, and pedestal-rich H. pylori infection, possibly caused by a higher level of action of CagA in the abnormal epithelial cells. The data suggests a novel H. pylori virulence factor associated with “excessive plasma protein release”.

scholarly journals Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments

Gut ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 1793-1804 ◽  
Author(s):  
Jennifer M Noto ◽  
Abha Chopra ◽  
John T Loh ◽  
Judith Romero-Gallo ◽  
M Blanca Piazuelo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Genetic Variation ◽  
Prolonged Exposure ◽  
Dietary Factors ◽  
High Salt ◽  
Premalignant Lesions ◽  
H Pylori

ObjectiveHelicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease.DesignWhole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed.ResultsA total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034).ConclusionThese results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis.

scholarly journals Helicobacter pylori Eradication Therapy - Recent Trend in Research

2020 ◽  
Vol 20 (3) ◽  
pp. 210-217
Author(s):  
Heung Up Kim
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Gastric Mucosa ◽  
Drug Exposure ◽  
Eradication Therapy ◽  
Dual Therapy ◽  
Resistance Rate ◽  
H Pylori ◽  
Selection Of

It is well known that <i>Helicobacter pylori (H. pylori)</i> can cause peptic ulcer, mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, intestinal metaplasia, and ultimately, gastric cancer. Various studies have proven that <i>H. pylori</i>, which attaches to the gastric mucosa, is the cause of gastric cancer and can be eradicated using appropriate antibiotics. Since 2013, Japan has been carrying out national-led eradication treatment of <i>H. pylori</i> for the whole population. However, as drug exposure increases, the resistance rate to some antibiotics increases, and the pattern of antibiotic resistance varies from region to region. Therefore, the development of individualized antimicrobial therapies has become important since antibiotic resistance to <i>H. pylori</i> eradication is a problem worldwide. To help overcome this, remedies such as selection of antibiotics through susceptibility testing, selection of empirical treatment combinations appropriate for the region, dual therapy with high doses of amoxicillin, and the use of rifabutin or sitafloxacin with low antibiotic resistance have been studied. Potassium-competitive acid blocker has been reported to be more potent in inhibiting acid secretion than proton pump inhibitor, and its role in <i>H. pylori</i> eradication is expected. Drug formulations and regimens that are easy to take are being developed to increase compliance. New treatments such as spraying antibiotics directly to the gastric mucosa are being developed and studied.

scholarly journals Expression of Helicobacter pylori Virulence Factors and Associated Expression Profiles of Inflammatory Genes in the Human Gastric Mucosa

2007 ◽  
Vol 75 (11) ◽  
pp. 5118-5126 ◽  
Author(s):  
Sicheng Wen ◽  
Dominique Velin ◽  
Christian P. Felley ◽  
Likun Du ◽  
Pierre Michetti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Virulence Factors ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Bacterial Colonization ◽  
Expression Patterns ◽  
Human Gastric Mucosa ◽  
H Pylori

ABSTRACT Helicobacter pylori virulence factors have been suggested to be important in determining the outcome of infection. The H. pylori adhesion protein BabA2 is thought to play a crucial role in bacterial colonization and in induction of severe gastric inflammation, particularly in combination with expression of CagA and VacA. However, the influence of these virulence factors on the pathogenesis of H. pylori infection is still poorly understood. To address this question, the inflammatory gene expression profiles for two groups of patients infected with triple-negative strains (lacking expression of cagA, babA2, and vacAs1 but expressing vacAs2) and triple-positive strains (expressing cagA, vacAs1, and babA2 but lacking expression of vacAs2) were investigated. The gene expression patterns in the antrum gastric mucosa from patients infected with different H. pylori strains were very similar, and no differentially expressed genes could be identified by pairwise comparisons. Our data thus suggest that there is a lack of correlation between the host inflammatory responses in the gastric mucosa and expression of the babA2, cagA, and vacAs1 genes.

scholarly journals Genome Sequencing Reveals a Phage in Helicobacter pylori

mBio ◽  
2011 ◽  
Vol 2 (6) ◽  
Author(s):  
Philippe Lehours ◽  
Filipa F. Vale ◽  
Magnus K. Bjursell ◽  
Ojar Melefors ◽  
Reza Advani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Human Population ◽  
Bacterial Genome ◽  
Uv Treatment ◽  
Integrase Gene ◽  
Content Type ◽  
Geographic Regions ◽  
H Pylori

ABSTRACT Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, likely to grow as more genomes are sampled. Here we describe the draft genome sequence (63 contigs; 26× mean coverage) of H. pylori strain B45, isolated from a patient with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The major finding was a 24.6-kb prophage integrated in the bacterial genome. The prophage shares most of its genes (22/27) with prophage region II of Helicobacter acinonychis strain Sheeba. After UV treatment of liquid cultures, circular DNA carrying the prophage integrase gene could be detected, and intracellular tailed phage-like particles were observed in H. pylori cells by transmission electron microscopy, indicating that phage production can be induced from the prophage. PCR amplification and sequencing of the integrase gene from 341 H. pylori strains from different geographic regions revealed a high prevalence of the prophage (21.4%). Phylogenetic reconstruction showed four distinct clusters in the integrase gene, three of which tended to be specific for geographic regions. Our study implies that phages may play important roles in the ecology and evolution of H. pylori. IMPORTANCE Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population, and while most of the infected individuals do not develop disease, H. pylori infection doubles the risk of developing gastric cancer. An abundance and diversity of viruses (phages) infect microbial populations in most environments and are important mediators of microbial diversity. Our finding of a 24.6-kb prophage integrated inside an H. pylori genome and the observation of circular integrase gene-containing DNA and phage-like particles inside cells upon UV treatment demonstrate that we have discovered a viable H. pylori phage. The additional finding of integrase genes in a large proportion of screened isolates of diverse geographic origins indicates that the prevalence of prophages may have been underestimated in H. pylori. Since phages are important drivers of microbial evolution, the discovery should be important for understanding and predicting genetic diversity in H. pylori.

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