Expression of 120 kilodalton protein and cytotoxicity in Helicobacter pylori.

Crabtree, Jean E.; Figura, Natale; Taylor, Jennifer; Bugnoli, M; Armellini, D.; Tompkins, David

doi:10.1136/jcp.45.8.733

Cited by 91 publications

(48 citation statements)

References 7 publications

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“…Pathogenicity has been associated with adhesion to the gastric epithelium (7,24,43), urease production (36), a vacuolating cytotoxin (10,11,13), and the action of phospholipases (31). However, knowledge of the basic metabolism of H. pylori is meager.…”

Section: Comentioning

confidence: 99%

Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori

et al. 1995

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CO 3؊ fixation activity, which was shown to be due to the isotope exchange reaction of pyruvate:flavodoxin oxidoreductase (EC 1.2.7.1), was present. The purified enzyme is composed of four subunits of 47, 36, 24, and 14 kDa. N-terminal sequence analysis showed that this enzyme is related to a recently recognized group of four-subunit pyruvate:ferredoxin oxidoreductases previously known only from hyperthermophiles. This enzyme from H. pylori was found to mediate the reduction of a number of artificial electron acceptors in addition to a flavodoxin isolated from H. pylori extracts, which is likely to be the in vivo electron acceptor. Indirect evidence that the enzyme is capable of in vitro reduction of the anti-H. pylori drug metronidazole was also obtained.Helicobacter pylori is a microaerophilic, gram-negative, motile, curved or spiral bacterium, isolated from the mucous layer overlying the human gastric epithelium (35,53). To date, eleven Helicobacter species have been isolated from a range of mammals (15,20,32). The organism is now accepted as the etiological agent for type B gastritis, and extensive evidence suggests a link with duodenal and gastric ulcer diseases (17,21,25,47,52). Individuals with long-term infections may also be at increased risk of developing gastric carcinoma (44).Enzyme activities identified in this bacterium include catalase, cytochrome oxidase, superoxide dismutase, and phospholipase, and it is a constitutive producer of a potent urease (18,23). Pathogenicity has been associated with adhesion to the gastric epithelium (7,24,43), urease production (36), a vacuolating cytotoxin (10,11,13), and the action of phospholipases (31). However, knowledge of the basic metabolism of H. pylori is meager. This organism exhibits limited glucose utilization (39, 41), but it is reported to contain pentose phosphate (38) and Entner-Douderoff pathways (8,42). Recently, utilization of glucose as a carbon and energy source in a defined medium has been shown (48). Active fumarate catabolism, generating malate and succinate from fumarate initially, followed by the formation of lactate, acetate, formate, and alanine, has been demonstrated (40). Suspensions of intact cells have been shown to generate lactate, ethanol, alanine, acetate, and CO 2 from pyruvate (8). This organism also requires elevated levels of CO 2 for growth, and it has been suggested that potent urease activity in part feeds this requirement (22). HCO 3 Ϫ is used in de novo synthesis of pyrimidines, but the demand for CO 2 considerably exceeds that of HCO 3 Ϫ . Gaseous CO 2 cannot be replaced by the addition of bicarbonate to the medium (22).Microorganisms exhibiting dependence on elevated CO 2 levels are termed capneic or capnophilic. Perhaps the best examples of pathogenic capnophiles are Neisseria spp. The enzymes known to be involved in CO 2 assimilation by Neisseria spp. are carbonic anhydrase (34) and phosphoenolpyruvate (PEP) carboxylase (12). Pyruvate carboxylase, PEP carboxykinase, and PEP carboxytransphosphorylase have not been dete...

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Section: Comentioning

confidence: 99%

Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori

et al. 1995

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“…Experience with other bacterial pathogens lead us to believe that H. pylori strain-specific factors may influence the pathogenicity of different H. pylori, such as vacuolating cytotoxin (VacA) and cytotoxin-associated protein (CagA), which have been identified [8][9][10][11][12]. Only 50% to 65% of H. pylori strains produce an 87kDa cytotoxin that induces vacuolation of HeLa or primary gastric epithelial cells in vitro [9,11,13].…”

mentioning

confidence: 99%

cagA positive Helicobacter pylori in Brazilian children related to chronic gastritis

Gatti

Labio²,

Silva³

et al. 2006

Braz J Infect Dis

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Helicobacter pylori is a spiral-shaped Gram-negative bacterium. It colonizes the gastric mucosa of humans and persists for decades if not treated. Helicobacter pylori infection affects more than half of the world's population and invariably results in chronic gastritis. The cagA gene is present in about 60 to 70% of H. pylori strains; it encodes a high-molecular-weight protein (120 to 140 kDa) and several investigators have noted a correlation between strains that possess cagA and the severity of gastric mucosal inflammation. We examined the relation between cagA status in H. pylori strains and chronic gastritis with inflammatory processes in children from Marília, São Paulo, Brazil. Onehundred-twenty-one children were analyzed histopathologically and by polymerase chain reaction (PCR) to detect H. pylori and cagA. We then looked for an association between cagA presence and inflammatory infiltration. Using histology and PCR, we found 47% H. pylori positive infection; 29 children were diagnosed with chronic gastritis, while 28 showed normal mucosa by histopathological analysis. CagA presence was genotyped in both groups, and an inflammatory infiltrate was studied in all infected children with chronic gastritis. We found cagA strains in 20 of 29 (69%) children with chronic gastritis and 18 of 28 (64%) with normal mucosa, demonstrating a strong relationship between the strains and the inflammatory process. We found a positive association between an inflammatory process associated with H. pylori of cagA+ strains and chronic gastritis development.

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“…One H. pylori characteristic that has been linked to more intensive tissue responses is the high-molecular-mass (120-to 140-kDa) CagA protein (14,53). Encoded by cagA (11,65) and recognized by serum antibodies in persons carrying cagA ϩ strains (12,16), serum and mucosal antibodies to CagA are significantly more prevalent among patients with peptic ulceration than among those with gastritis alone (9,12,16).…”

mentioning

confidence: 99%

Anti-CagA Immunoglobulin G Responses Correlate with Interleukin-8 Induction in Human Gastric Mucosal Biopsy Culture

Ando

Pérez-Pérez

Kusugami

et al. 2000

Clin Diagn Lab Immunol

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Helicobacter pylori persists in the human stomach despite eliciting both cellular and humoral immune responses and inducing proinflammatory cytokines. To determine whether local humoral and cytokine responses are related to each other and to histologic responses, we studied 66 Japanese patients who underwent gastroscopy. Using specific enzyme-linked immunosorbent assays, we examined gastric antral mucosal-organ biopsy culture supernatants to assess interleukin-6 (IL-6) and interleukin-8 (IL-8) levels and antibody responses to H. pylori whole-cell antigens CagA, HspA, and HspB. Of the patients studied, 11 were H. pylori negative and 55 were H. pylori positive; by PCR, all strains were cagA ؉ . As expected, compared to H. pylori-negative patients, H. pylori-positive patients had significantly higher humoral responses to all H. pylori antigens and had higher IL-8 (47.8 ؎ 3.5 versus 10.1 ؎ 4.3 ng/mg of biopsy protein; P < 0.001) and IL-6 levels (2.8 ؎ 0.3 versus 0.26 ؎ 0.2 ng/mg of protein; P < 0.001). Among the H. pylori-positive patients, supernatant anti-CagA immunoglobulin G (IgG) levels were significantly associated with H. pylori density (P < 0.005) and neutrophil infiltration (P < 0.005) scores. Anti-CagA immunoglobulin A levels were correlated with intestinal metaplasia (P < 0.05). Mononuclear cell infiltration scores were significantly associated with supernatant IL-6 levels (P < 0.005) and with IgG responses to whole-cell antigens (P < 0.05). Supernatant IL-8 levels were significantly associated with anti-CagA IgG (r ‫؍‬ 0.75, P < 0.001). Anti-CagA responses correlated with neutrophil infiltration, intestinal metaplasia, H. pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts.

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Expression of 120 kilodalton protein and cytotoxicity in Helicobacter pylori.

Cited by 91 publications

References 7 publications

Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori

Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori

cagA positive Helicobacter pylori in Brazilian children related to chronic gastritis

Anti-CagA Immunoglobulin G Responses Correlate with Interleukin-8 Induction in Human Gastric Mucosal Biopsy Culture

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