Allelic variation in Helicobacter pylori: progress but no panacea

Mj, Blaser

doi:10.1136/gut.45.4.477

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…Because these motifs are associated with tyrosine phosphorylation of CagA protein, they were investigated to determine if they might provide markers of more-severe disease outcome as a result of increased H. pylori-host epithelial cell interactions. Polymorphisms within cagA may affect the biological function of the protein and might explain the lack of a consistent correlation between cagA and disease severity previously noted (6,23,24). Initial identification of TPMs was based on a small number of diverse isolates of H. pylori, so the purpose of the present study has been to investigate TPM variation and frequency in a larger sample of isolates from peptic ulcer as well as NUD patients.…”

Section: Discussionmentioning

confidence: 99%

“…About 68% of strains isolated from dyspeptics in England have cagA present in the genome (24), and similar or higher frequencies have been reported in many other countries (16,17,20). Nevertheless, cagA status alone is insufficient to reliably predict either virulence or association with gastric ulcer (6,15,19,25).…”

mentioning

confidence: 99%

“…Gastric infections with H. pylori have a worldwide distribution, with current prevalence rates about 35% in England and Wales (32) and more than 75% in many developing countries (26). No single pathogenicity factor has yet been proved to be uniquely associated with the ability of H. pylori to cause gastroduodenal ulcer disease or cancer (6,11). The presence of the cytotoxin-associated gene (cagA), encoded in the 40-kb cag pathogenicity island (cag PAI), and the presence of signal and midregion alleles of the vacuolating cytotoxin (vacA) gene are markers for type I strains of H. pylori (7).…”

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confidence: 99%

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Identification ofcagATyrosine Phosphorylation DNA Motifs inHelicobacter pyloriIsolates from Peptic Ulcer Patients by Novel PCR-Restriction Fragment Length Polymorphism and Real-Time Fluorescence PCR Assays

et al. 2003

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Cag pathogenicity island-containing Helicobacter pylori (type I) induces signal transduction pathways resulting in tyrosine phosphorylation of proteins adjacent to the site of bacterial adhesion on host gastric epithelial cells. Conventional block PCR-restriction fragment length polymorphism (RFLP) and real-time LightCycler (LC) PCR hybridization assays, validated by direct sequencing, were designed to test for the presence of three nucleotide sequences corresponding to tyrosine phosphorylation motifs (TPMs) A, B, and C in 84 isolates of H. pylori type I from patients in England. Overall, the PCR assays demonstrated that one or more TPMs were present in 62 strains (75%). Motif A was common (71% of strains), whereas motifs B and C were rarer (8% of strains). Strains lacking a TPM were typically vacuolating cytotoxin genotype vacA m2. Motif A was widely distributed in relation to disease severity and was more commonly (but not significantly [P ‫؍‬ 0.071]) associated with gastric ulcer than with duodenal ulcer (86 versus 56%). The LC hybridization assay provided a rapid means of detecting all three motifs, but RFLP analysis was more specific for TPM-A. TPMs provide novel additional strain markers for defining cagA variation, including identification of RFLP types within TPM-A. The presence of a particular TPM was not of direct diagnostic value, either singly or in combination, but the higher proportion of TPM-A strains in gastric ulcer patients merits further investigation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Identification ofcagATyrosine Phosphorylation DNA Motifs inHelicobacter pyloriIsolates from Peptic Ulcer Patients by Novel PCR-Restriction Fragment Length Polymorphism and Real-Time Fluorescence PCR Assays

et al. 2003

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“…Some strains causing nonulcer dyspepsia have regions of the promoter of cagA gene deleted (28), although this gene has long been regarded as a marker for the functionality of the cag-PAI. However, due to rearrangements often inhibiting cagA, it does not seem to be a reliable indicator of the virulence spectrum of strains (7). Other members of the cag-PAI have also been scrutinized for their involvement in virulence characteristics.…”

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confidence: 99%

ThecagPathogenicity Island ofHelicobacter pyloriIs Disrupted in the Majority of Patient Isolates from Different Human Populations

et al. 2004

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The cag pathogenicity island (cag-PAI) is one of the major virulence determinants of Helicobacter pylori. The chromosomal integrity of this island or the lack thereof is speculated to play an important role in the progress of the gastroduodenal pathology caused by H. pylori. We determined the integrity of the cag-PAI by using specific flanking and internally anchored PCR primers to know the biogeographical distribution of strains carrying fully integral cag-PAI with proinflammatory behavior in vivo. Genotypes based on eight selected loci were studied in 335 isolates obtained from eight different geographic regions. The cag-PAI appeared to be disrupted in the majority of patient isolates throughout the world. Conservation of cag-PAI was highest in Japanese isolates (57.1%). However, only 18.6% of the Peruvian and 12% of the Indian isolates carried an intact cag-PAI. The integrity of cag-PAI in European and African strains was minimal. All 10 strains from Costa Rica had rearrangements. Overall, a majority of the strains of East Asian ancestry were found to have intact cag-PAI compared to strains of other descent. We also found that the cagE and cagT genes were less often rearranged (18%) than the cagA gene (27%). We attempted to relate cag-PAI rearrangement patterns to disease outcome. Deletion frequencies of cagA, cagE, and cagT genes were higher in benign cases than in isolates from severe ulcers and gastric cancer. Conversely, the cagA promoter and the left end of the cag-PAI were frequently rearranged or deleted in isolates linked to severe pathology. Analysis of the cag-PAI genotypes with a different biogeoclimatic history will contribute to our understanding of the pathogen-host interaction in health and disease.

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“…The aim of the present study was to analyse diversity amongst the short vacA insert sequences using new sequences and all currently available online database sequences. Although the presence or absence of vacA inserts provides the basis of a widely used scheme for H. pylori strain genotyping (Atherton et al, 1999b), the clinical significance of a particular genotype remains unclear, and consequently vacA typing is of limited value in predicting severity of infection and possible clinical outcome (Go et al, 1998;Blaser, 1999;Höcker & Hohenberger, 2003). Analyses of the 892 sequences of the vacA s and m alleles in the dataset compiled for this study demonstrated that insert sequences were highly conserved according to a number of criteria, notably their location within vacA, overall nucleotide length, G+C content and similarities within allelic families in nucleotide and hence in predicted amino acid sequences.…”

Section: Discussionmentioning

confidence: 99%

Geographical conservation of short inserts in the signal and middle regions of the Helicobacter pylori vacuolating cytotoxin gene

Owen¹,

Xerry²

2007

Microbiology

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Short nucleotide sequence inserts within the signal (s) and mid (m) regions of the vacuolating cytotoxin gene (vacA) of Helicobacter pylori provide the basis for defining the allelic forms widely used for strain typing and as markers for toxin functionality and severity of interactions with host gastric epithelial cells. Here 484 signal region and 411 mid-region sequences (new and from public databases) from 32 countries were analysed to determine the effect of geographical location on insert diversity, which is currently undefined. Short (27 bp) inserts of 52 mol% G+C from 201 sequences (98 %) of the s2 allelic family encoded a highly conserved nine amino acid sequence irrespective of geographical origin. The longer (75 bp) mid-region insert of 38 mol% G+C in 255 sequences of the m2 allelic family was more diverse and represented by 23 peptide variants, with one predominant sequence (MRI type 4) representing 62 % of inserts. Mid-region inserts were widespread throughout European/North American (Western) sequences in the dataset whereas a lower insert frequency was a geographical feature of East Asian sequences. Each insert was preceded by an associated conserved motif that provided a marker of the insertion sites within vacA, and facilitated identification of the Chinese m2b genotype. It is concluded that the observed sequence conservation supports the continued global use of vacA genotyping, and that inserts could have a functional significance in the mature protein, particularly the s2 form of the toxin, as the same combination of signal and mid-region insert type and preinsert motif was highly conserved.

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Allelic variation in Helicobacter pylori: progress but no panacea

Cited by 4 publications

References 26 publications

Identification ofcagATyrosine Phosphorylation DNA Motifs inHelicobacter pyloriIsolates from Peptic Ulcer Patients by Novel PCR-Restriction Fragment Length Polymorphism and Real-Time Fluorescence PCR Assays

Identification ofcagATyrosine Phosphorylation DNA Motifs inHelicobacter pyloriIsolates from Peptic Ulcer Patients by Novel PCR-Restriction Fragment Length Polymorphism and Real-Time Fluorescence PCR Assays

ThecagPathogenicity Island ofHelicobacter pyloriIs Disrupted in the Majority of Patient Isolates from Different Human Populations

Geographical conservation of short inserts in the signal and middle regions of the Helicobacter pylori vacuolating cytotoxin gene

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