Pathogenic Mechanisms of Helicobacter pylori: Production of Cytotoxin

Figura, Natale; Bugnoli, M; Cusi, Maria Grazia; Pucci, Annalisa; Lusini, P; Quaranta, S.; Barberi, A; Rossolini, A; Addabbo, Tommaso; Magistris, T De; Rappuoli, Rino; Marri, Laura; Musmanno, R. A.; Russi, M; Guarna, Massimo; Losi, Monica

doi:10.1007/978-3-642-75315-2_13

Cited by 23 publications

(17 citation statements)

References 4 publications

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“…pylori induce the formation of vacuoles in the cytoplasm ofdifferent cell lines. This vacuolation leads to cell and tissue necrosis, which is believed to play a central role in the establishment of the inflammation of the gastric mucosa by recruiting polimorphonuclear leukocytes (2)(3)(4)(5)(6)(7).…”

Section: Discussionmentioning

confidence: 99%

“…Biopsies of H. pylori-colonized stomach epithelium show cellular swelling, expansion of endosomal compartments, and extensive vacuolation (4). A vacuolar degeneration of epithelial cells, followed by cell death, is induced in vitro by H. pylori bacterial extracts (5)(6)(7). The luminal pH of these vacuoles is acidic, as deduced from the uptake of neutral red, a membrane-permeant amine that becomes protonated in the vacuolar lumen, and from the potentiating effect of ammonia (8).…”

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confidence: 99%

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Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.

Papini

Bernard

Milia

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

220

179

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Pathogenic strains of Helicobacter pylon cause progressive vacuolatlon and death of epithelial cells. To identify the nature of vacuoles, the distribution of markers of various membrane traffic compartments was studied. Vacuoles derive from the endocytic pathway since they include the fluid-phase marker Lucifer yellow. Early endosome markers such as rab5, trerrin, and trnsferrin receptor, as well as the lysosomal hydrolase cathepsin D, are excluded from these structures. In contrast, the vacuolar membrane is specifically stained by ity-purified antibodies against rab7, a small GTPase, localized to late endosomal compartments. The labeling of rab7 on vacuolar membranes increases as vacuolation progresses, without a concomitant increase of cellular rab7. Cell vacuolation is inhibited by the microtubule-depolymerizing agents nocodazole and colchicine. Taken together, these findins indicate that the vacuoles specifically originate from late endosomal compartments.Strong evidence indicates that toxigenic strains of Helicobacter pylori play a major role in the development of type B gastritis, peptic ulcers, and gastric adenocarcinoma (1-3). Biopsies of H. pylori-colonized stomach epithelium show cellular swelling, expansion of endosomal compartments, and extensive vacuolation (4). A vacuolar degeneration of epithelial cells, followed by cell death, is induced in vitro by H. pylori bacterial extracts (5-7). The luminal pH of these vacuoles is acidic, as deduced from the uptake of neutral red, a membrane-permeant amine that becomes protonated in the vacuolar lumen, and from the potentiating effect of ammonia (8). Two virulence factors, produced by pathogenic strains of H. pylori are thought to be mainly responsible for this cell degeneration and death: a urease and a cytotoxin (3,4,7,8). The urease hydrolyzes urea and the ammonia produced permeates membranes, as neutral red does, and accumulates as ammonium ions inside intracellular acidic compartments, thus causing their osmotic swelling (9-11). However important, this process alone cannot account for the manyfold increase in vacuole volume, because, without membrane addition, it would lead to vacuole rupture.Recently a cytotoxin has been isolated from culture supernatants of a virulent strain of H. pylori (12) and shown to cause vacuolation in vitro (12) and in vivo (13). The genes encoding this protein (vacA; H. pylori vacuolating toxin A), and a bacterial antigen (cagA) characteristic of H. pylori pathogenic strains, have been recently cloned and sequenced, and they share no similarity with any other known protein (13,14). Thus, the molecular mechanism of action of vacA and the sequence of events leading to vacuolar cell degeneration and death remain largely obscure.The inhibition of vacuole formation by bafilomycins, specific inhibitors of the vacuolar-type ATPase proton pump (V-ATPase) (15), indicates that vacuoles originate from intracellular compartments endowed with a V-ATPase, such as endosomes, lysosomes, or the trans-Golgi network (TGN) (16)(17)(18)....

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.

Papini

Bernard

Milia

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

220

179

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“…The presence of infection by cytotoxic strains was evaluated by a Western blotting (WB) assay performed according to a previously described technique 13 . As a positive control, an anti-recombinant Cag-A serum raised in rabbit (kindly provided by Drs.…”

Section: Methodsmentioning

confidence: 99%

“…The aims of the present study were: 1) to investigate the prevalence of H. pylori infection and Cag-A positivity in a large population of short children compared to the auxologically normal population and verify, in this way, a possible impact of H. pylori infection on statural growth; 2) to investigate the possible relationship between H. pylori infection and growth hormone deficiency; 3) to assess the reliability of IgG titration compared to 13 C-UBT in this pediatric population.…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori Infection and Cytotoxic Antigen Associated Gene "A" Status in Short Children

Cacciari¹,

Menegatti²,

Salardi³

et al. 1999

Journal of Pediatric Endocrinology and Metabolism

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“…As the CagA protein can be secreted onto the bacterial surface and also released into the culture supernatant even in the absence of a typical leader peptide sequence (11,(24)(25)(26)(27)(28), CagA secretion is thought to be exported by a secindependent secretion system (11,19). In this study, we confirmed that the 145-kD protein (and the 130-135-kD protein) was also secreted into the culture supernatant from various H. pylori strains when attached to the epithelial cells, and we identified the 145-kD protein (and the 130-135-kD proteins) as CagA.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori CagA protein can be tyrosine phosphorylated in the gastric epithelial cells

Azuma¹,

Asahi²,

Ito³

et al. 2000

Gastroenterology

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Pathogenic Mechanisms of Helicobacter pylori: Production of Cytotoxin

Cited by 23 publications

References 4 publications

Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.

Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.

Helicobacter pylori Infection and Cytotoxic Antigen Associated Gene "A" Status in Short Children

Helicobacter pylori CagA protein can be tyrosine phosphorylated in the gastric epithelial cells

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