Dataset Information

Variations in the multimerization region of the Helicobacter pylori cytotoxin CagA affect virulence.

ABSTRACT: Helicobacter pylori colonizes the human stomach by infecting gastric epithelial cells. It is the primary cause of peptic ulcer disease and gastric cancer (GC). Cytotoxin-associated gene A (CagA) is a virulence factor produced by H. pylori. Strains positive for the CagA protein are associated with more severe gastric diseases. The 3' region of the cagA gene exhibits heterogeneity with respect to tyrosine phosphorylation motifs (EPIYA) and CagA multimerization motifs (CM). CagA proteins are categorized as either Western or Eastern based on EPIYA sequences. CM motifs are also identified as Western and Eastern based on CM sequences identified in Western and East Asian countries. It has been suggested that CagA proteins possessing an Eastern CM type are associated with less severe gastric disorders. In the present study, the effects of two CagA peptides with different CM motifs on cell function were compared: CagA with a Western and Eastern CM motif (CagA-WE), and CagA with two Western CM motifs (CagA-WW). CagA sequences were fused with green fluorescent protein (GFP) to form GFP-CagA fusion proteins. GFP-CagA and GFP control constructs were transfected into human gastric adenocarcinoma cells (AGS). GFP-CagA expression was verified by immunoblotting and immunofluorescence. The results demonstrated that, following 18 h, the CagA-WE-transfected cells were less adherent compared with the CagA-WW transfected cells. CagA has also been reported to cause cell elongation in AGS cells. In the current study, cell elongation was more frequent in the CagA-WW-transfected cells compared with the CagA-WE transfected cells (8.34 vs. 3.97% cells, respectively). The CagA peptides did not affect proliferation or apoptosis rates. These results suggest that different CM motif types may affect CagA virulence.

SUBMITTER: Ahire D

PROVIDER: S-EPMC5403285 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Variations in the multimerization region of the Helicobacter pylori cytotoxin CagA affect virulence.

Ahire Daiva D Alston Tricia T Raffaniello Robert R

Oncology letters 20170102 3

Helicobacter pylori colonizes the human stomach by infecting gastric epithelial cells. It is the primary cause of peptic ulcer disease and gastric cancer (GC). Cytotoxin-associated gene A (CagA) is a virulence factor produced by H. pylori. Strains positive for the CagA protein are associated with more severe gastric diseases. The 3' region of the cagA gene exhibits heterogeneity with respect to tyrosine phosphorylation motifs (EPIYA) and CagA multimerization motifs (CM). CagA prote ...[more]

PMID: 28454275

Similar Datasets

Project description:BackgroundHelicobacter pylori (H. pylori) colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer. However, although the prevalence of H. pylori is high in Africa, the incidence of gastric cancer is low, and this phenomenon is called to be African enigma. The CagA protein produced by H. pylori is the most studied virulence factor. The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala (EPIYA) patterns and CagA-multimerization (CM) motifs.AimTo better understand the EPIYA patterns and CM motifs of the cagA gene.MethodsGastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic, from which 120 H. pylori strains were cultured. After the bacterial DNA extraction, the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing. The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing (MLST). Peptic ulcer disease and gastric cancer were identified via endoscopy, and gastric cancer was confirmed by histopathology. Histological scores of the gastric mucosa were evaluated using the updated Sydney system.ResultsAll CagA-positive strains carried the Western-type CagA according to the identified EPIYA patterns. Twenty-seven kinds of CM motifs were observed. Although the typical Western CM motif (FPLKRHDKVDDLSKVG) was observed most frequently, the typical East Asian CM motif (FPLRRSAAVNDLSKVG) was not observed. However, "FPLRRSAKVEDLSKVG", similar to the typical East Asian CM motif, was found in 21 strains. Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis (P = 0.034), we termed it Africa1-CM (Af1-CM). A few hpEurope strains carried the Af1-CM motif, but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif (P = 0.030). In 30 cagA-positive strains, the "GKDKGPE" motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment, and there was a significant association between strains with the hpAfrica1 population and those containing the "GKDKGPE" motif (P = 0.018). In contrast, there was no significant association between the CM motif patterns and histological scores and clinical outcomes.ConclusionWe found the unique African CM motif in Western-type CagA and termed it Africa1-CM. The less toxicity of this motif could be one reason to explain the African enigma.

Dataset Information

Variations in the multimerization region of the Helicobacter pylori cytotoxin CagA affect virulence.

Publications

Variations in the multimerization region of the <i>Helicobacter pylori</i> cytotoxin CagA affect virulence.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets