scholarly journals Vacuolating Cytotoxin of Helicobacter pylori Plays a Role during Colonization in a Mouse Model of Infection

2001 ◽  
Vol 69 (2) ◽  
pp. 730-736 ◽  
Author(s):  
Nina R. Salama ◽  
Glen Otto ◽  
Lucy Tompkins ◽  
Stanley Falkow
Keyword(s):  
Helicobacter Pylori ◽  
Mouse Model ◽  
Bacterial Load ◽  
Gastric Disease ◽  
Infection Model ◽  
Vacuolating Cytotoxin ◽  
Ulcer Disease ◽  
Culture Cells ◽  
H Pylori ◽  
Mouse Model Of Infection

ABSTRACT Helicobacter pylori, the causative agent of gastritis and ulcer disease in humans, secretes a toxin called VacA (vacuolating cytotoxin) into culture supernatants. VacA was initially characterized and purified on the basis of its ability to induce the formation of intracellular vacuoles in tissue culture cells. H. pyloristrains possessing different alleles of vacA differ in their ability to express active toxin. Those strains expressing higher toxin levels are correlated with more severe gastric disease. However, the specific role(s) played by VacA during the course of infection and disease is not clear. We have used a mouse model of H. pylori infection to begin to address this role. A null mutation of vacA compromises H. pylori in its ability to initially establish infection. If an infection by a vacAmutant is established, the bacterial load and degree of inflammation are similar to those associated with an isogenic wild-type strain. Thus, in this infection model, vacA plays a role in the initial colonization of the host, suggesting that strains of H. pylori expressing active alleles of vacA may be better adapted for host-to-host transmission.

scholarly journals Peptidoglycan Deacetylation in Helicobacter pylori Contributes to Bacterial Survival by Mitigating Host Immune Responses

2010 ◽  
Vol 78 (11) ◽  
pp. 4660-4666 ◽  
Author(s):  
Ge Wang ◽  
Susan E. Maier ◽  
Leja F. Lo ◽  
George Maier ◽  
Shruti Dosi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Bacterial Load ◽  
Host Cells ◽  
Infection Model ◽  
Wild Type ◽  
Mouse Infection Model ◽  
Mouse Infection ◽  
H Pylori

ABSTRACT An oxidative stress-induced enzyme, peptidoglycan deacetylase (PgdA), in the human gastric pathogen Helicobacter pylori was previously identified and characterized. In this study, we constructed H. pylori pgdA mutants in two mouse-adapted strains, X47 and B128, to investigate the role of PgdA in vivo (to determine the mutants’ abilities to colonize mice and to induce an immune response). H. pylori pgdA mutant cells showed increased sensitivity to lysozyme compared to the sensitivities of the parent strains. We demonstrated that the expression of PgdA was significantly induced (3.5-fold) when H. pylori cells were in contact with macrophages, similar to the effect observed with oxidative stress as the environmental inducer. Using a mouse infection model, we first examined the mouse colonization ability of an H. pylori pgdA mutant in X47, a strain deficient in the major pathway (cag pathogenicity island [PAI] encoded) for delivery of peptidoglycan into host cells. No animal colonization difference between the wild type and the mutant was observed 3 weeks after inoculation. However, the pgdA mutant showed a significantly attenuated ability to colonize mouse stomachs (9-fold-lower bacterial load) at 9 weeks postinoculation. With the cag PAI-positive strain B128, a significant colonization difference between the wild type and the pgdA mutant was observed at 3 weeks postinoculation (1.32 × 104 versus 1.85 × 103 CFU/gram of stomach). To monitor the immune responses elicited by H. pylori in the mouse infection model, we determined the concentrations of cytokines present in mouse sera. In the mice infected with the pgdA mutant strain, we observed a highly significant increase in the level of MIP-2. In addition, significant increases in interleukin-10 and tumor necrosis factor alpha in the pgdA mutant-infected mice compared to the levels in the wild-type H. pylori-infected mice were also observed. These results indicated that H. pylori peptidoglycan deacetylation is an important mechanism for mitigating host immune detection; this likely contributes to pathogen persistence.

scholarly journals Clinical Relevance of Helicobacter pylori Infection

2021 ◽  
Vol 10 (16) ◽  
pp. 3473
Author(s):  
Irena Mladenova
Keyword(s):  
Helicobacter Pylori ◽  
Age Groups ◽  
Acid Resistance ◽  
Clinical Indication ◽  
Clinical Aspects ◽  
Gastric Disease ◽  
Upper Gastrointestinal Endoscopy ◽  
World Population ◽  
Ulcer Disease ◽  
H Pylori

Helicobacter pylori (H. pylori) is a Gram-negative helical, microaerophilic bacterium which colonizes the antrum and body of the stomach, surviving in its harsh environment through mechanisms of acid resistance and colonization factors. It infects approximately 50% of the world population. Although the prevalence of this infection varies from country to country, as well as between different ethnic, social or age groups, it is estimated that about 50% of the human population only carries this microorganism. While H. pylori has been found to play a major etiological and pathogenic role in chronic gastritis, peptic ulcer disease and gastric cancer, its importance for many types of extra-gastric disease needs to be further investigated. The choice of tests to diagnose H. pylori infection, defined as invasive or non-invasive, depends on the clinical indication as to whether to perform upper gastrointestinal endoscopy. Focusing on bacterial eradication, the treatment should be decided locally based on the use of antibiotics and documented antibiotic resistance. The author provides an overview of the current state of knowledge about the clinical aspects of H. pylori infection, especially its diagnostic and therapeutic management.

scholarly journals Analysis of Helicobacter pylori Genotypes in Afghani and Iranian Isolates

2010 ◽  
Vol 59 (1) ◽  
pp. 61-66 ◽  
Author(s):  
HOSSEIN DABIRI ◽  
MEHDI BOLFION ◽  
AKBAR MIRSALEHIAN ◽  
MARYAM REZADEHBASHI ◽  
FERESHTEH JAFARI ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Clinical Outcomes ◽  
Positive Culture ◽  
Chain Reaction ◽  
Vacuolating Cytotoxin ◽  
Ulcer Disease ◽  
Polymerase Chain ◽  
H Pylori ◽  
Iranian Patients

The geographical variation in Helicobacter pylori genotypes is an observed phenomenon. Cytotoxin associated genes A (cagA) and E (cagE), and vacuolating cytotoxin (vacA) genotypes of H. pylori are associated with peptic ulcer disease (PUD). This study compared the distribution of these genotypes in Iranian and Afghani isolates and their association with clinical outcomes. H. pylori infected patients, as proven by positive culture, were recruited prospectively. A total of 70 patients, 55 Iranian (26 men and 29 women, mean age 48 +/- 18 years) and 15 Afghani immigrants (13 men and 2 women, mean age 34.8 +/- 11 years) living in Tehran, Iran were enrolled in this study. DNA was extracted from isolated H. pylori and polymerase chain reaction was carried out to determine the cagA and cagE status and vacA alleles. The number of gastric cancer, peptic ulcer and gastritis cases was 11, 23 and 36, respectively. The cagA positive isolates were more common in Iranian (67%) than Afghani isolates (60%). cagE was positive in 53% of Afghani compared to 51% of Iranian isolates. The most common vacA s-region genotype was s1; 80% in Afghani and 67% in Iranian. The slml was a frequently observed genotype in Afghani strains (53%) while s1m2 (47%) was more common in strains isolated from Iranian patients. There is a difference in the H. pylori strains between Iranian and Afghani groups, for instance Iranian isolates were similar to European isolates while Afghani isolates were similar to isolates from India. However, there was no significant association between cagA, cagE and vacA genotypes and clinical outcomes in Iranian and Afghani patients.

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 Antibody-Mediated Protection against Infection with Helicobacter pylori in a Suckling Mouse Model of Passive Immunity

2009 ◽  
Vol 77 (11) ◽  
pp. 5116-5129 ◽  
Author(s):  
Rebecca J. Gorrell ◽  
Roy M. Robins-Browne
Keyword(s):  
Helicobacter Pylori ◽  
Mouse Model ◽  
Bacterial Load ◽  
Passive Immunity ◽  
Minor Role ◽  
Milk Analysis ◽  
Suckling Mouse ◽  
Antibody Isotype ◽  
H Pylori ◽  
Culture Negative

ABSTRACT Studies of active immunization against Helicobacter pylori indicate that antibodies play a minor role in immunity. There is also evidence, however, that the translocation of antibodies in the stomach may be insufficient to achieve functional antibody levels in the gastric lumen. We have used a suckling mouse model of passive immunity to determine if perorally delivered antibodies can protect against infection with H. pylori. Female C57BL/6 mice were immunized parenterally with formalin-fixed cells of three clinical isolates of H. pylori (3HP) or the mouse-adapted H. pylori strain SS1 before mating. Their pups were challenged with the SS1 strain at 4 days of age and left to suckle before determination of bacterial loads 14 days later. Compared to age-matched controls, pups suckled by 3HP-vaccinated dams were significantly protected against infection (>95% reduction in median bacterial load; P < 0.0001). Pups suckled by SS1-vaccinated dams were also significantly protected in terms of both median bacterial load (>99.5% reduction; P < 0.0001) and the number of culture-negative pups (28% versus 2% for immune and nonimmune cohorts, respectively; P < 0.0001). Similar results were obtained with pups suckled by dams immunized with a urease-deficient mutant of SS1. Fostering experiments demonstrated that protection was entirely attributable to suckling from an immunized dam, and antibody isotype analysis suggested that protection was mediated by the immunoglobulin G fraction of immune milk. Analysis of the bacterial loads in pups sampled before and after weaning confirmed that infection had been prevented in culture-negative animals. These data indicate that antibodies can prevent colonization by H. pylori and suppress the bacterial loads in animals that are colonized.

scholarly journals Identification of Markers for Helicobacter pylori Strains Isolated from Children with Peptic Ulcer Disease by Suppressive Subtractive Hybridization

2006 ◽  
Vol 74 (7) ◽  
pp. 4064-4074 ◽  
Author(s):  
Mónica Oleastro ◽  
Lurdes Monteiro ◽  
Philippe Lehours ◽  
Francis Mégraud ◽  
Armelle Ménard
Keyword(s):  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Peptic Ulcer Disease ◽  
Subtractive Hybridization ◽  
Suppressive Subtractive Hybridization ◽  
Ulcer Disease ◽  
Lipopolysaccharide Biosynthesis ◽  
The Difference ◽  
H Pylori

ABSTRACT Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori infection. However, the disease can develop earlier, and rare cases have been observed in children, suggesting that these H. pylori strains may be more virulent. We used suppressive subtractive hybridization for comparative genomics between H. pylori strains isolated from a 5-year-old child with duodenal ulcer and from a sex- and age-matched child with gastritis only. The prevalence of the 30 tester-specific subtracted sequences was determined on a collection of H. pylori strains from children (15 ulcers and 30 gastritis) and from adults (46 ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P = 0.008) and jhp0870 (80.0% versus 36.7%, P = 0.015), were highly associated with PUD in children and a third sequence, jhp0828, was less associated (40.0% versus 10.0%, P = 0.048). Among adult strains, none of the 30 sequences was associated with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma strains than in PUD strains from children and adults, the difference being statistically significant for jhp0870. In conclusion, two H. pylori genes were identified as being strongly associated with PUD in children, and their putative roles as an outer membrane protein for jhp0870 and in lipopolysaccharide biosynthesis for jhp0562, suggest that they may be novel virulence factors of H. pylori.

scholarly journals Effects of Oral Vaccination and Immunomodulation by Cholera Toxin on Experimental Helicobacter pylori Infection, Reinfection, and Gastritis

2002 ◽  
Vol 70 (8) ◽  
pp. 4621-4627 ◽  
Author(s):  
S. Raghavan ◽  
A.-M. Svennerholm ◽  
J. Holmgren
Keyword(s):  
Helicobacter Pylori ◽  
Cholera Toxin ◽  
Mononuclear Cells ◽  
Oral Treatment ◽  
Bacterial Load ◽  
Oral Immunization ◽  
Initial Infection ◽  
Fold Reduction ◽  
H Pylori

ABSTRACT Therapeutic vaccination is an attractive strategy to control infection and disease caused by Helicobacter pylori. In mice infected with H. pylori we have studied the protective effect of oral immunization with an H. pylori lysate preparation given together with the mucosal adjuvant cholera toxin (CT), both against the initial infection and against a later reinfection challenge. We have also examined the effects of treatment with the CT adjuvant alone on H. pylori infection and reinfection. Specific immunization with lysate was found to result in a sixfold reduction of the extent (bacterial load) of the primary infection and also to provide similar levels of protection against reinfection. However, these effects were associated with severe postimmunization gastritis. In contrast, oral treatment with CT alone at the time of initial infection, while unable to suppress the initial infection, gave rise to a 20-fold reduction in bacterial load upon reinfection without causing any associated gastric inflammation. Both the infected animals that were specifically immunized and those that were treated with CT only displayed increased in vitro proliferative responses of mononuclear cells to H. pylori antigens. Antibody levels in response to H. pylori were on the other hand only marginally increased after treatment with CT, whereas they were markedly elevated after immunization with lysate plus CT, with a rise in both (Th2-driven) immunoglobulin G1 (IgG1) and, especially, (Th1-driven) IgG2a antibodies. The results illustrate the complex balance between protection and harmful inflammation after postinfection vaccination against H. pylori as studied in a mouse model.

scholarly journals Effect of Helicobacter pylori on Polymorphonuclear Leukocyte Migration across Polarized T84 Epithelial Cell Monolayers: Role of Vacuolating Toxin VacA and cagPathogenicity Island

2000 ◽  
Vol 68 (9) ◽  
pp. 5225-5233 ◽  
Author(s):  
Véronique Hofman ◽  
Vittorio Ricci ◽  
Antoine Galmiche ◽  
Patrick Brest ◽  
Patrick Auberger ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Polymorphonuclear Leukocyte ◽  
Broth Culture ◽  
Intestinal Cell ◽  
T84 Cells ◽  
Vacuolating Cytotoxin ◽  
Intestinal Cell Line ◽  
H Pylori

ABSTRACT Helicobacter pylori infection can induce polymorphonuclear leukocyte (PMNL) infiltration of the gastric mucosa, which characterizes acute chronic gastritis. The mechanisms underlying this process are poorly documented. The lack of an in vitro model has considerably impaired the study of transepithelial migration of PMNL induced by H. pylori. In the present work, we used confluent polarized monolayers of the human intestinal cell line T84 grown on permeable filters to analyze the epithelial PMNL response induced by broth culture filtrates (BCFs) and bacterial suspensions from different strains of H. pylori. We have evaluated the role of the vacuolating cytotoxin VacA and of the cagpathogenicity island (PAI) of H. pylori in PMNL migration via their effects on T84 epithelial cells. We noted no difference in the rates of PMNL transepithelial migration after epithelial preincubation with bacterial suspensions or with BCFs of VacA-negative or VacA-positive H. pylori strains. In contrast, PMNL transepithelial migration was induced after incubation of the T84 cells with cag PAI-positive and cagE-positiveH. pylori strains. Finally, PMNL migration was correlated with a basolateral secretion of interleukin-8 by T84 cells, thus creating a subepithelial chemotactic gradient for PMNL. These data provide evidence that the vacuolating cytotoxin VacA is not involved in PMNL transepithelial migration and that the cag PAI, with a pivotal role for the cagE gene, provokes a transcellular signal across T84 monolayers, inducing a subepithelial PMNL response.

scholarly journals Prevalence of Helicobacter pylori infection among patients undergoing upper gastrointestinal endoscopy

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Vudumula Vijaya Lakshmi
Keyword(s):  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Normal Population ◽  
Gastric Ulcers ◽  
Upper Gastrointestinal Endoscopy ◽  
Contributing Factors ◽  
Duodenal Ulcers ◽  
Female Ratio ◽  
Ulcer Disease ◽  
H Pylori

Helicobacter pylori (H. pylori) has a role in the multifactorial etiology of peptic ulcer disease. A link between H. pylori infection and duodenal ulcer disease is now established. Other contributing factors and their interaction with the organism may initiate the ulcerative process. The fact that eradication of H. pylori infection leads to a long-term cure in the majority of duodenal ulcer patients and the fact that the prevalence of infection is higher in ulcer patients than in the normal population are cogent arguments in favor of it being the primary cause of the ulceration. This study was under taken at the Department of surgery, Narayana medical college, Nellore from January 2007 to July 2008. A total of 150 patients with duodenal ulcers, gastric ulcers, antral gastritis, gastric carcinoma and dyspepsia of any kind were studied. Maximum number of cases were in the age group of 31 years to 50 years among both sexes and number of cases gradually decreased after 50 years of age in males and females. Males were more in number and male to female ratio is (2.75:1) approximately 3:1.

scholarly journals Features of the endoscopic picture in paediatric gastroduodenal diseases caused by Helicobacter pylori

2020 ◽  
Vol 10 (3) ◽  
pp. 543-550
Author(s):  
Sh. T. Turdieva ◽  
E. A. Shamansurova
Keyword(s):  
Helicobacter Pylori ◽  
Inflammatory Diseases ◽  
Gastric Wall ◽  
Duodenogastric Reflux ◽  
Chronic Atrophic Gastritis ◽  
Endoscopic Examination ◽  
Ulcer Disease ◽  
Functional Studies ◽  
H Pylori ◽  
Endoscopic Picture

The aim of the study was to examine the features of the endoscopic picture in the upper digestive tract mucosa in paediatric chronic gastroduodenal pathology (CGDP) associated with Helicobacter pylori. Materials and methods. There were examined 286 patients, aged 6–15 years. Diagnostic criteria for chronic gastroduodenal pathology were anamnestic as well as instrumental and functional studies data: gastric fractional intubation, esophagogastroduodenoscopy (EPGDS) with endoscopic pH-metry without biopsy, and ultrasound examination of abdominal organs. H. pylori testing was carried out by two unrelated methods such as respiratory test and a immunochromatographic fecal test. Results. Detection of H. pylori in children with CGDP peaked in patients with peptic gastric and duodenal ulcer (up to 87.5%, p < 0.05). The main endoscopic signs were edema, hyperaemia and contact bleeding, as well as local haemorrhage were the major endoscopic signs of inflammation in the stomach and duodenum mucosa. Atrophic mucosal lesions were characterized by thinning, pale colour together with transilluminated submucosal vessels. Non-atrophic antral gastritis was featured with delayed gastric emptying, antral stasis and pyloric spasm. In contrast, hypotension of the gastric wall, duodenogastric reflux and decreased motility were more typical to chronic atrophic gastritis. Major endoscopic feature in patients with H. pylori infection was presented by dominant atrophic changes combined with gastroduodenal reflux (77.6%, p < 0.05) compared to patients without H. pylori infection. Conclusion. Detection of HP infection was peaked in children with CGDP coupled to peptic ulcer disease compared to patients with inflammatory diseases (p < 0.05). Endoscopic examination in HP-positive patients showed that atrophic changes were found by 4-fold more frequently together with gastroduodenal reflux compared to patients without HP infection (p < 0.05).

Sign in / Sign up

Export Citation Format

Share Document