Conservation of the cag pathogenicity island of Helicobacter pylori: Associations with vacuolating cytotoxin allele and IS605 diversity

Slater, E.; Owen, Robert J.; Williams, M. P.; Pounder, R. E.

doi:10.1016/s0016-5085(99)70281-7

Cited by 46 publications

(56 citation statements)

References 30 publications

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“…A recent study, in which paired antral and corpus isolates differed with respect to polymorphism of cagA locus, supports this idea (9). However, these paired isolates were identical with respect (23,28,37,47). Apart from this, one can also guess the involvement of certain dedicated gene products (such as DNA helicases), encoded by chromosomal regions flanking the cag-PAI, in propagating the island (16).…”

Section: Discussionmentioning

confidence: 90%

“…The involvement of these genes and others in eliciting a strong immune response has also been contested (45). Rearrangements in cag-PAI in H. pylori isolates in different countries have been reported in isolation (5,22,23,26,28,37,40,47). However, there are no comprehensive data available on the abundance of intact versus rearranged cag-PAI in strains inhabiting geographically and culturally distinct patient populations on a global scale.…”

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

et al. 2004

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“…The primers and PCR conditions for the two assays for cagA (a marker for the 39 end of the cag pathogenicity island and for the cagI region) were as described previously using the F1/B1 primers and the D008/R008 primer sets (Slater et al, 1999;Owen et al, 2001a). Vacuolating cytotoxin (vacA) genotyping based on signal and mid-region alleles was performed as previously described (Atherton et al, 1999;Owen et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

Analysis of geospecific markers for Helicobacter pylori variants in patients from Japan and Nigeria by triple-locus nucleotide sequence typing

Owen¹,

Xerry²,

Gotada

et al. 2004

Microbiology

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Human migrations and geographical separation over long periods may have resulted in ecologically distinct populations of Helicobacter pylori infecting individuals in different continents. This study used nucleotide sequence analysis with the aim of defining population-specific genomic motifs in isolates from East Asian and African dyspeptic patients. Sequences of internal fragments (542-627 bp) of three housekeeping genes (ureI, ahpC and atpA) were analysed for 85 isolates from individuals in Japan and China (30 isolates), Nigeria and South Africa (14 isolates), the United Kingdom (32 isolates), and nine miscellaneous reference strains. Phylogenetic analyses showed a high degree of intra-set relatedness amongst sequences from the Japanese and Nigerian isolates, with each robustly segregated as distinct lineages irrespective of cagA presence and vacA allelic type. All strains had unique combined sequence types except for identical paired (antrum/corpus) isolates. Population-specific polymorphisms were identified within each gene which were combined to provide unique motifs defining the Japanese and Nigerian regional populations. The alleles were present at variable frequencies in UK and South African isolates. The findings provide unique evidence of positive selection for conserved nucleotide sites linked to the geographical separation in Japan of a strain subpopulation for which we propose the designation H. pylori geovar 'orientalis'.

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“…Among H. pylori isolates, the presence of insertion elements causes differences in the compositions of the cag island; the consequent cag instability may produce differences in pathogenicity and host adaptability within a bacterial strain. The cag island can be present as a single uninterrupted unit or can be divided into two segments (cagI and cagII) by an interposed insertion element (IS605); moreover, it can be partially or totally deleted (8,24,28,33). Although deletions of the cag island have been reported (17,18,28,31) and cag instability has been shown for mice (34), detailed analyses of the cag island in human isolates are still insufficient.…”

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Heterogeneity of cag Genotypes in Helicobacter pylori Isolates from Human Biopsy Specimens

Tomasini¹,

Zanussi²,

Sozzi

et al. 2003

J Clin Microbiol

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The Helicobacter pylori chromosomal cluster of genes known as the cytotoxin-associated gene (cag) island may have different compositions in infecting strains. In this study, we analyzed 150 single colonies obtained from gastric biopsy specimens from 10 patients infected with cagA-positive H. pylori strains and sweep isolates (isolates harvested with sweep in different points of the plate) from 6 patients infected with cagA-negative strains. Three loci in the cag island (cagA, cagE, and virB11) and the conserved gene glmM (ureC) were investigated by PCR. The levels of anti-H. pylori and anti-CagA antibodies in patient sera were also measured. For subjects infected with cagA-negative strains, all sweep isolates were also negative for cagE and virB11, suggesting the complete absence of the cag island. For subjects infected with cagA-positive strains, most of the isolates were positive for all three genes studied, whereas 24.7% of the isolates had a partial or total deletion of the cag island. cagA, cagE, and virB11 were, respectively, present in 87.3, 77.3, and 90% of the colonies. The deletion of virB11 was always associated with the deletion of cagA and/or cagE. H. pylori colonies with different cag genotypes were isolated within a single gastric biopsy specimen from 3 of the 10 patients and were further characterized by random amplified polymorphic DNA (RAPD) analysis and by sequencing of an arbitrarily selected gene segment. Although the colonies had different cag genotypes, their RAPD profiles were highly similar within each patient, and the nucleotide sequences of the selected gene segment were identical. All of the patients had detectable antibodies against H. pylori, and 9 of 10 had anti-CagA antibodies. In conclusion, we show that a single infecting H. pylori strain may include variable proportions of colony subtypes with different cag genotypes. The extension of our analysis to patients with well-characterized gastric diseases may provide significant information on the relationship between cag genotypes and clinical outcomes of H. pylori infections.Helicobacter pylori is a gram-negative spiral bacterium that colonizes the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma (25).Although the pathogenesis of H. pylori infection is not completely understood, several putative virulence factors may contribute to mucosal damage (5, 26). The cytotoxin-associated gene (cag) island, an approximately 40-kb cluster of genes in the H. pylori chromosome, probably was inherited by horizontal transfer from an unknown microorganism. Many of the cag genes have homology to those of other bacteria encoding virulence factors and a type IV secretion system. Therefore, they may play an important role in microbial virulence and pathogenicity (6, 10). Among H. pylori isolates, the presence of insertion elements causes differences in the compositions of the cag island; the consequent cag instability may produce d...

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Conservation of the cag pathogenicity island of Helicobacter pylori: Associations with vacuolating cytotoxin allele and IS605 diversity

Cited by 46 publications

References 30 publications

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

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

Analysis of geospecific markers for Helicobacter pylori variants in patients from Japan and Nigeria by triple-locus nucleotide sequence typing

Heterogeneity of cag Genotypes in Helicobacter pylori Isolates from Human Biopsy Specimens

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