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Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori.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 ta ...201122044679
pathogenesis of helicobacter pylori infection.helicobacter pylori infections and clinical outcome are dependent on sophisticated interactions between the bacteria and its host. crucial bacterial factors associated with pathogenicity comprise a type iv secretion system encoded by the cag pathogenicity island, the effector protein caga, the vacuolating cytotoxin (vaca), peptidoglycan, lipopolysaccharide (lps), γ-glutamyl transpeptidase (ggt), protease htra, and the adhesins baba, saba, and others. the high number of these factors and allelic ...201121896081
comparative genomics and proteomics of helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen.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.201020219135
helicobacter pylori colonization of the human gastric epithelium: a bug's first step is a novel target for us.after helicobacter pylori enters the stomach, three steps are vital for infection: (i) establishing colonization; (ii) evading host immunity; and (iii) invading gastric mucosa; the last step is what is associated with diverse outcomes. urease activity and motility mediated by the flagella of h. pylori are important in harboring colonies beneath the gastric mucus in niches adjacent to the epithelium. several putative adhesins attach the organism to the gastric epithelium and prompt the succeeding ...201020136973
celecoxib inhibits helicobacter pylori colonization-related factors.to investigate the effect of celecoxib, a selective cox-2 inhibitor, on helicobacter pylori (h. pylori) colonization-related factors and its mechanism.201020143463
helicobacter pylori adhesion to gastric epithelial cells is mediated by glycan receptors.helicobacter pylori adhesion to gastric epithelial cells constitutes a key step in the establishment of a successful infection of the gastric mucosa. the high representation of outer membrane proteins in the bacterial genome suggests the relevance of those proteins in the establishment of profitable interactions with the host gastric cells. gastric epithelial cells are protected by a mucous layer gel, mainly consisting of the muc5ac and muc6 mucins. in addition to this protective role, mucins ha ...201020521012
peptides from pisum sativum l. enzymatic protein digest with anti-adhesive activity against helicobacter pylori: structure-activity and inhibitory activity against baba, saba, hpaa and a fibronectin-binding adhesin.identification of anti-adhesive peptides against helicobacter pylori obtained by enzymatic hydrolysis of seed proteins from pisum sativum l. (fabaceae).201020540145
complexomics study of two helicobacter pylori strains of two pathological origins: potential targets for vaccine development and new insight in bacteria metabolism.helicobacter pylori infection plays a causal role in the development of gastric mucosa-associated lymphoid tissue (malt) lymphoma (lg-malt) and duodenal ulcer (du). although many virulence factors have been associated with du, many questions remain unanswered regarding the evolution of the infection toward this exceptional event, lg-malt. the present study describes and compares the complexome of two h. pylori strains, strain j99 associated with du and strain b38 associated with lg-malt, using t ...201020610778
the mechanical binding strengths of helicobacter pylori baba and saba adhesins using an adhesion binding assay-elisa, and its clinical relevance in japan.to elucidate a potential role for h. pylori baba and saba adhesins in the pathogenesis of gastric mucosal lesions, the mbs of baba and saba was examined using an in-house aba-elisa. ninety isolates from japanese patients with gastric cancer (n= 43) and non-cancerous (n= 47) lesions were subjected to an aba-elisa which had been developed in-house, and sequential analysis of the baba2 middle region. the baba-mbs was significantly higher in the cancer than the non-cancer group (p= 0.019), but there ...201020646208
biochemical and functional characterization of helicobacter pylori vesicles.helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. adhesion of bacteria to the stomach mucosa is an important contributor to the vigour of infection and resulting virulence. h. pylori adheres primarily via binding of baba adhesins to abo/lewis b (leb) blood group antigens and the binding of saba adhesins to sialyl-lewis x/a (slex/a) antigens. similar to most gram-negative bacteria, h. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often ...201020659286
genetic diversity of the helicobacter pylori sialic acid-binding adhesin (saba) gene.a putative virulence factor, saba, a sialic acid-binding adhesin, has recently been characterized in helicobacter pylori from european isolates. however, little genetic information is available for saba genes in strains isolated from japanese patients. here, we investigated the presence of the saba gene in 23 h. pylori clinical isolates using polymerase chain reaction detection. it was found that 91.3% of h. pylori isolates examined contain the saba gene. sequence comparison and phylogenetic ana ...201021068478
molecular pathogenesis of helicobacter pylori infection: the role of bacterial virulence factors.helicobacter pylori is one of the most common pathogens affecting humankind, infecting approximately 50% of the world's population. of those infected, many will develop asymptomatic gastritis, but 10% develop gastric or duodenal ulcers. the clinical outcome of the infection may involve a combination of bacterial factors, host factors and environmental factors. in the process of development of gastritis, ulceration and cancer, several cellular and molecular steps follow each other. infection, aci ...201021088410
outer membrane protein expression profile in helicobacter pylori clinical isolates.the gram-negative gastric pathogen helicobacter pylori is equipped with an extraordinarily large set of outer membrane proteins (omps), whose role in the infection process is not well understood. the hop (helicobacter outer membrane porins) and hor (hop-related proteins) groups constitute a large paralogous family consisting of 33 members. the omps alpa, alpb, baba, saba, and hopz have been identified as adhesins or adherence-associated proteins. to better understand the relevance of these and o ...200919546190
identification of glycoprotein receptors within the human salivary proteome for the lectin-like baba and saba adhesins of helicobacter pylori by fluorescence-based 2-d bacterial overlay.because gastric infection by helicobacter pylori takes place via the oral route, possible interactions of this bacterium with human salivary proteins could occur. by using modified 1- and 2-d bacterial overlay, binding of h. pylori adhesins baba and saba to the whole range of salivary proteins was explored. bound salivary receptor molecules were identified by maldi-ms and by comparison to previously established proteome maps of whole and glandular salivas. by use of adhesin-deficient mutants, bi ...200919253298
prevalence of virulence-associated genotypes of helicobacter pylori and correlation with severity of gastric pathology in patients from western sicily, italy.in a bacterium like helicobacter pylori, which is characterized by a recombinant population structure, the associated presence of genes encoding virulence factors might be considered an expression of a selective advantage conferred to strains with certain genotypes and, therefore, a potentially useful tool for predicting the clinical outcome of infections. however, differences in the geographical and ethnic prevalence of the h. pylori virulence-associated genotypes can affect their clinical pred ...200918958508
fut2-null mice display an altered glycosylation profile and impaired baba-mediated helicobacter pylori adhesion to gastric mucosa.glycoconjugates expressed on gastric mucosa play a crucial role in host-pathogen interactions. the fut2 enzyme catalyzes the addition of terminal alpha(1,2)fucose residues, producing the h type 1 structure expressed on the surface of epithelial cells and in mucosal secretions of secretor individuals. inactivating mutations in the human fut2 gene are associated with reduced susceptibility to helicobacter pylori infection. h. pylori infects over half the world's population and causes diverse gastr ...200919706747
muc1 limits helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy.the bacterium helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and malt lymphoma. the cell-surface mucin muc1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of h. pylori in a murine infection model. we now demonstrate that by using the baba and saba adhesins, h. pylori bind muc1 isolated from human gastric cells and muc1 shed into gastric juice. both h. pylori carrying these adhesins, and beads coated with muc1 antibodies ...200919816567
[helicobacter pylori virulence factors except caga].study for helicobacter pylori pathogenesis has been already performed widely all over the world for about 20 years. this review summarized recent studies about virulence factors except caga/cag pai system. bacterial adhesion to gastric mucosa is critical for the persistent infection and baba, saba, oipa, alpa or alpb is involved. vaca (vacuolating cytotoxin) causes not only vacuolation of gastric epithelial cells but also stimulates apoptosis via a mitochondria-dependent pathway and is a potent ...200919999108
increasing evidence of the role of helicobacter pylori saba in the pathogenesis of gastroduodenal disease.although infection with helicobacter pylori always results in chronic active gastritis, only a fraction of those infected develop severe clinical disease. in addition, certain populations with high incidences of h. pylori infection, such as those in east asian countries, have high incidences of gastric cancer, while other highly infected populations, such as those in africa and south asia, do not. this phenomenon might be partially explained by differences in the genotypes of h. pylori; however, ...200819738347
pathogenesis of helicobacter pylori infection.the clinical outcome of helicobacter pylori infection is determined by a complex scenario of interactions between the bacterium and the host. the main bacterial factors associated with colonization and pathogenicity comprise outer membrane proteins including baba, saba, oipa, alpa/b, as well as the virulence factors caga in the cag pathogenicity island (cagpai) and the vacuolating cytotoxin vaca. the multitude of these proteins and allelic variation makes it extremely difficult to test the contr ...200818783516
infection of saba-positive h. pylori does not induce anti-lewis x antibody in host.h. pylori uses the sialic acid-binding adhesin (saba) to recognize lewis x (lex) antigen of gastric epithelial cells. saba is associated with nonopsonic activation of human neutrophils. the aims of this study were to examine the association of bacterial saba status to the presence of anti-lex antibody in host and the grade of gastritis.200818705343
helicobacter pylori induces beta3gnt5 in human gastric cell lines, modulating expression of the saba ligand sialyl-lewis x.chronic helicobacter pylori infection is recognized as a cause of gastric cancer. h. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid-binding adhesin (saba), which binds the carbohydrate structure sialyl-lewis x. sialyl-lewis x expression in the gastric epithelium is induced during persistent h. pylori infection, suggesting that h. pylori modulates host cell glycosylation patterns for enhanced adhesion. here, we evaluate changes in the glycosylation-related ...200818483624
four modes of adhesion are used during helicobacter pylori binding to human mucins in the oral and gastric niches.helicobacter pylori causes peptic ulcer disease and gastric cancer, and the oral cavity is likely to serve as a reservoir for this pathogen. we investigated the binding of h. pylori to the mucins covering the mucosal surfaces in the niches along the oral to gastric infection route and during gastric disease and modeled the outcome of these interactions.200818321298
expression of the helicobacter pylori adhesin saba is controlled via phase variation and the arsrs signal transduction system.adaptation to the acidic microenvironment, and adherence to mucosal epithelium, are essential for persistent colonization of the human stomach by helicobacter pylori. the expression of saba, an adhesin implicated in the ability of h. pylori to adhere to the host gastric epithelium, can be modulated by phase variation via slipped-strand mispairing in repetitive nucleotide tracts located in both the promoter region and the coding region. this study demonstrates the occurrence of phase variation at ...200818667556
clinical relevance of helicobacter pylori saba genotype in japanese clinical isolates.the clinical outcome of helicobacter pylori infection is strongly affected by the bacterial genotype. the aim of this study was to assess the relationship between the status of h. pylori sialic acid-binding adhesin (saba) and the severity of gastric inflammation and diseases.200718031386
pathogenesis of helicobacter pylori infection.the clinical outcome of helicobacter pylori infection is determined by a complex interaction between the bacterium and the host. the main bacterial factors associated with pathogenicity comprise outer membrane proteins, including baba, saba, oipa, alpa, and alpb, the vacuolating cytotoxin vaca and the products of cagpai. the multitude of putative virulence factors makes it extremely difficult to test the contribution of each individual factor. much effort has been put into identifying the mechan ...200717727454
saba is the h. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.adherence of helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (saba) and cognate sialylated/fucosylated glycans on the host cell surface. by in situ hybridization, h. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and rhesus monkeys. in vivo adherence of h. pylori to erythrocytes may require molecular mechanisms similar to t ...200617121461
isolation and characterization of a competence operon associated with transformation and adhesion in helicobacter pylori.to identify adhesion-associated loci, we screened 1500 mutant strains of a helicobacter pylori mutant library. a mutant that showed decreased adhesion to two gastric epithelial cell lines was identified. inverse polymerase chain reaction (pcr) revealed that the interrupted locus of this mutant was an hp0015 homolog of h. pylori strain 26695. dna sequencing and reverse-transcription pcr revealed that hp0015 and two downstream genes (hp0016 and hp0017) were a transcriptional unit. deletion and com ...200617045509
helicobacter pylori saba adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein.the human pathogen helicobacter pylori expresses two dominant adhesins; the lewis b blood group antigen binding adhesin, baba, and the sialic acid-binding adhesin, saba. these adhesins recognize specific carbohydrate moieties of the gastric epithelium, i.e. the lewis b antigen, le(b), and the sialyl-lewis x antigen, sle(x), respectively, which promote infection and inflammatory processes in the gastroduodenal tract. to assess the contribution of each of baba, saba and the neutrophil activating p ...200616758245
interaction between host gastric sialyl-lewis x and h. pylori saba enhances h. pylori density in patients lacking gastric lewis b antigen.we tested whether the interaction between host gastric le(x) antigen and the saba protein of h. pylori determined gastric colonization density.200616405531
helicobacter pylori outer membrane proteins and gastroduodenal disease.a number of helicobacter pylori outer membrane proteins (omps) undergo phase variations. this study examined the relation between omp phase variations and clinical outcome.200616322107
adherence properties of helicobacter pylori: impact on pathogenesis and adaptation to the host.the adherence of the human gastric pathogen helicobacter pylori to the gastric mucosa is widely assumed to play a substantial role in initial colonization and long-term persistence in the human stomach. in the past, a couple of putative adhesins were identified, most of which were members of the large outer membrane protein (omp) family of h. pylori. among these, the baba protein was shown to recognize the leb antigen, which is presented as a dominant surface structure in the gastric mucosa. the ...200516173498
identification and characterization of binding properties of helicobacter pylori by glycoconjugate arrays.the microaerophilic bacterium helicobacter pylori is well established for its role in development of different gastric diseases. bacterial adhesins and corresponding binding sites on the epithelial surface allow h. pylori to colonize the gastric tissue. in this investigation, the adhesion of h. pylori to dot blot arrays of natural glycoproteins and neoglycoproteins was studied. adhesion was detected by overlay with fluorescence-labeled bacteria on immobilized (neo)glycoproteins. the results conf ...200515716466
the sialic acid binding saba adhesin of helicobacter pylori is essential for nonopsonic activation of human neutrophils.infiltration of neutrophils and monocytes into the gastric mucosa is a hallmark of chronic gastritis caused by helicobacter pylori. certain h. pylori strains nonopsonized stimulate neutrophils to production of reactive oxygen species causing oxidative damage of the gastric epithelium. here, the contribution of some h. pylori virulence factors, the blood group antigen-binding adhesin baba, the sialic acid-binding adhesin saba, the neutrophil-activating protein hp-nap, and the vacuolating cytotoxi ...200515689619
[helicobacter pylori saba adhesin in japan]. 200516363510
h. pylori infection: bacterial virulence factors and cytokine gene polymorphisms as determinants of infection outcome.the gram negative bacterium h. pylori infects the human stomach worldwide, invariably causing mucosal inflammation. in the majority of cases, h. pylori-associated gastritis remains the only clinical manifestation of the infection, which might cause, otherwise, peptic ulcer, gastric adenocarcinoma. or maltoma. the balance between the bacterial virulence machinery and the host response to the infection determines the different clinical outcomes. the main bacterial virulence factors comprise adhesi ...200415307635
the functional status of the helicobacter pylori sabb adhesin gene as a putative marker for disease outcome.helicobacter pylori factors that contribute to disease outcome are largely unknown, but intimate contact with host cells mediated by outer membrane proteins is thought to play an important role. expression of the outer membrane proteins oipa, hopz, saba, and sabb is regulated by phase-variable dinucleotide repeats in the coding regions of the respective genes. we have evaluated the correlation between the expression status of these four genes and disease outcome of h. pylori infection in a dutch ...200415068418
gnotobiotic transgenic mice reveal that transmission of helicobacter pylori is facilitated by loss of acid-producing parietal cells in donors and recipients.helicobacter pylori is acquired during childhood, but its mode of transmission remains unclear. a genotyped h. pylori isolate (hp1) that expresses two classes of adhesins was introduced into the stomachs of three types of germ-free fvb/n mice to model factors that may affect spread of h. pylori in humans. normal mice represented human hosts with normal gastric acid production. transgenic animals expressing human alpha-1,3/4-fucosyltransferase in their gastric pit cells represented humans with no ...200414998521
helicobacter pylori and complex gangliosides.recognition of sialic acid-containing glycoconjugates by the human gastric pathogen helicobacter pylori has been repeatedly demonstrated. to investigate the structural requirements for h. pylori binding to complex gangliosides, a large number of gangliosides were isolated and characterized by mass spectrometry and proton nuclear magnetic resonance. ganglioside binding of sialic acid-recognizing h. pylori strains (strains j99 and ccug 17874) and knockout mutant strains with the sialic acid bindin ...200414977958
evaluation of the association of nine helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma.helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (malt) lymphoma. although the cag pathogenicity island, especially the caga gene, has been linked with adenocarcinoma, few data concerning h. pylori pathogenic factors involved in low-grade gastric malt lymphoma are available. the goal of this study was to analyze the prevalence of and correlation between genes coding for seven h. pylori vir ...200414742532
rhesus monkey gastric mucins: oligomeric structure, glycoforms and helicobacter pylori binding.mucins isolated from the stomach of rhesus monkey are oligomeric glycoproteins with a similar mass, density, glycoform profile and tissue localization as human muc5ac and muc6. antibodies raised against the human mucins recognize those from monkey, which thus appear to be orthologous to those from human beings. rhesus monkey muc5ac and muc6 are produced by the gastric-surface epithelium and glands respectively, and occur as three distinct glycoforms. the mucins are substituted with the histo blo ...200414736333
helicobacter pylori saba adhesin in persistent infection and chronic inflammation.helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. here, we identify sialyl-dimeric-lewis x glycosphingolipid as a receptor for h. pylori and show that h. pylori infection induced formation of sialyl-lewis x antigens in gastric epithelium in humans and in a rhesus monkey. the corresponding sialic acid-binding adhesin (saba) was isolated with the "retagging" method, and the underlying saba gene (jhp662/hp0725) was identified. ...200212142529
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