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Journal of Clinical Microbiology, September 1998, p. 2597-2603, Vol. 36, No. 9
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Expanding Allelic Diversity of Helicobacter
pylori vacA
Leen-Jan
van
Doorn,1,*
Céu
Figueiredo,1,2
Ricardo
Sanna,1
Salvador
Pena,3
Peter
Midolo,4
Enders K. W.
Ng,5
John C.
Atherton,6
Martin J.
Blaser,7 and
Wim G. V.
Quint1
Delft Diagnostic Laboratory, 2625 AD
Delft,1 and
Free University Hospital,
Department of Gastroenterology, Amsterdam,3 The
Netherlands;
IPATIMUP and Medical Faculty, University of Porto,
Porto, Portugal2;
Monash Medical
Center, Victoria, Australia4;
Prince of Wales
Hospital, Hong Kong, China5;
Division
of Infectious Diseases, Vanderbilt University, Nashville,
Tennessee7; and
Division of
Gastroenterology and Institute of Infections and Immunity,
University Hospital, Nottingham, United Kingdom6
Received 27 February 1998/Returned for modification 28 May
1998/Accepted 11 June 1998
 |
ABSTRACT |
The diversity of the gene encoding the vacuolating cytotoxin
(vacA) of Helicobacter pylori was analyzed in
98 isolates obtained from different geographic locations. The studies
focused on variation in the previously defined s and m regions of
vacA, as determined by PCR and direct sequencing.
Phylogenetic analysis revealed the existence of four distinct types of
s-region alleles: aside from the previously described s1a, s1b, and s2
allelic types, a novel subtype, designated s1c, was found. Subtype s1c
was observed exclusively in isolates from East Asia and appears to be
the major s1 allele in that part of the world. Three different allelic
forms (m1, m2a, and m2b) were detected in the m region. On the basis of
sequence alignments, universal PCR primers that allow effective
amplification of the s and m regions from H. pylori
isolates from all over the world were defined. Amplimers were
subsequently analyzed by reverse hybridization onto a line probe assay
(LiPA) that allows the simultaneous and highly specific hybridization
of the different vacA s- and m-region alleles and tests for
the presence of the cytotoxin-associated gene (cagA). This
PCR-LiPA method permits rapid analysis of the vacA and
cagA status of H. pylori strains for
clinical and epidemiological studies and will facilitate identification
of any further variations.
| |
INTRODUCTION |
Helicobacter pylori is a
medically important bacterium that is involved in the pathogenesis of
peptic ulcer disease and that is associated with gastric
carcinoma. The ecological niche of H. pylori
is the human stomach, where it establishes a long-term colonization of
the mucosa (9). The use of DNA fingerprinting techniques has revealed substantial genetic heterogeneity among different isolates (1, 25, 40), and the total
variation of H. pylori is greater than that in
other bacteria that have been studied (18). During the past
decade, the products of several H. pylori genes
that play a role in disease have been identified (7, 8, 43).
The cytotoxin-associated gene (cagA), which is not present
in every H. pylori strain (12, 15, 37),
is a marker for a genomic pathogenicity (cag) island of
about 40 kbp (11) whose presence is associated with more
severe clinical outcomes (6, 22, 27). The cag
island contains genes encoding proteins that enhance the virulence of
the strain, for example, by inducing cytokine production by the host
(2, 11, 38).
A cytotoxin that damages epithelial cells by inducing the formation of
vacuoles is encoded by vacA (10, 13, 14, 16, 23, 28,
30, 36). Although vacA is present in all H. pylori strains, it contains at least two variable parts
(4). The s region (encoding the signal peptide) exists as s1
or s2 allelic types. Among type s1 strains, subtypes s1a and s1b have
been identified. The m (middle) region occurs as m1 or m2 allelic
types. There is a close association between the presence of
cagA and vacA type s1, because most s1 strains
are cagA positive (4). The particular vacA s and m genotype is a marker of the pathogenicity of an
individual strain, since in vitro production of the cytotoxin, in vivo
epithelial damage, and peptic ulcer disease are all related to the
vacA genotype (4, 5).
Analysis of total genomic DNA or polymorphic regions usually shows
extremely large variations among isolates. However, different DNA
segments of the bacterial genome are not uniform in their variability. The heterogeneity of single-copy genes encoding
enzymes is usually restricted due to functional constraints on the
encoded proteins, and mutations tend to be synonymous.
Virulence-associated genes may be subjected to the selection of
variants with altered biological specificity. This may lead to
phenotypically distinct variants which can be distinguished at the
genetic level. In the present study, the variability of the s and m
regions of the cytotoxin-encoding vacA gene was investigated
among H. pylori strains from various geographic
locations. On the basis of sequence data, a PCR-based assay for
analysis of vacA allelic variation that permits rapid genotyping of H. pylori strains from diverse parts
of the world was developed.
| |
MATERIALS AND METHODS |
H. pylori isolates.
A total of 98 H. pylori isolates were obtained from different
locations around the world, including Australia (n = 6), Costa Rica (n = 4), China (n = 6),
Hong Kong (n = 21), Japan (n = 5), The
Netherlands (n = 12), Peru (n = 6),
Portugal (n = 25), Thailand (n = 5),
the United States (n = 6), and New Zealand (where
strains were obtained from Maoris, who are native inhabitants of New
Zealand of Polynesian origin; n = 2). Each isolate was
obtained from a different patient who underwent gastroscopy and gastric
biopsy, usually due to symptoms of dyspepsia. After the primary
isolation and identification of the gastric organisms as H. pylori, the strains were frozen at 
70°C until their use in
these studies. Subsequently, the bacteria were cultured on Trypticase
soy agar plates containing 5% sheep blood (Becton Dickinson) for 3 to
5 days at 37°C under microaerobic conditions (5% O2,
10% CO2, 80% N2). The H. pylori cells were harvested from the plates by suspension in 2 ml of a sterile 0.9% NaCl solution and were pelleted by centrifugation at 10,000 × g for 2 min. The cells were resuspended in
400 µl of 10 mM Tris-HCl (pH 8.0)-5 mM EDTA-0.1% sodium dodecyl
sulfate (SDS)-0.1 mg of proteinase K per ml and were incubated for 2 to 4 h at 55°C. Proteinase K was inactivated by incubation at
95°C for 10 min. The lysate was diluted 1/100 in sterile water and was directly used for PCR.
PCRs.
All primers used in this study are presented in Table
1. To amplify the vacA s
region, primers VA1F and VA1xR were used, resulting in a fragment of
176 bp for type s1 variants and a fragment of 203 bp for type s2
variants. Primers HPMGF and HPMGR were used to amplify part of the
vacA m region and yielded fragments of 401 and 476 bp for
type m1 and type m2, respectively. These fragments were used for
sequence analysis. Subsequently, on the basis of these m region
sequences, novel primers that amplify a smaller part of the m region
and that have higher sensitivities than HPMGF and HPMGR were designed.
This new m-region PCR comprised a mixture of forward primers MF1.1,
MF1.2, MF1.3, and MF1.4 and reverse primer MR1 and resulted in the
amplification of fragments of 107 and 182 bp for m1 and m2 strains,
respectively.
The presence of cagA was detected with primers cagAF and
cagAR, yielding a product of 183 bp. All PCR mixtures consisted of 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 1.5 mM MgCl2,
deoxynucleotides at concentrations of 200 µM each, 25 pmol of the
forward and reverse primers, and 1.5 U of AmpliTaq Gold DNA polymerase
(Perkin-Elmer) in a final volume of 50 µl. One microliter of DNA from
the culture lysates was used in each reaction mixture. The mixture was
covered with mineral oil to prevent evaporation. The PCR program
comprised 9 min of predenaturation at 94°C, followed by 40 cycles of
30 s at 94°C, 45 s at 50°C, and 45 s at 72°C and a
final incubation at 72°C for 5 min. PCR products were inspected by
electrophoresis on 2% agarose gels.
Sequence analysis.
The PCR products were sequenced with the
Thermo-Sequenase cycle sequencing kit (Amersham), by using Cy-labelled
primers, followed by electrophoresis on an ALF-express automatic
sequencer (Pharmacia Biotech). Sequences were analyzed with PCGene
software (Intelligenetics Inc.) and the Clustal program. Phylogenetic
analyses were performed with various modules of the Phylogeny Inference
Package (Phylip), version 3.5c. (17). Pairwise sequence
comparisons were performed with the program DNADIST by using the Kimura
two-parameter setting, and matrices of sequence distances were
produced; phylogenetic relationships were further analyzed by the
NEIGHBOR-JOINING method. The program Treecon (39) was
used to create a graphic output. Substitution rates were calculated
with Windows Easy Tree software (version 1.31; developed by J. Dopazo,
1997 [available at http://www.tdi.es]). Classification of m-region
sequences into types and subtypes was based on the frequency
distribution of nucleotide sequence distances, as calculated from the
distance matrices, as has been described for the classification of
hepatitis C virus types and subtypes (31). Three distinct
levels of sequence variability are recognized. The major groupings of
sequence variants (m1 or m2) are designated types, whereas the more
closely related groups are termed subtypes (m2a or m2b). Sequences
belonging to the same subtype show even more limited heterogeneity and
are designated isolates.
Reverse hybridization LiPA.
PCR products were analyzed by
reverse hybridization by a line probe assay (LiPA) (32).
This assay consists of a nitrocellulose strip that contains dT-tailed
oligonucleotide probes (Table 2) immobilized as parallel lines. For each strain, 10 µl of each PCR
product (containing biotin at the 5' end of each primer) was denatured
by the addition of an equal amount of 400 mM NaOH-10 mM EDTA in a
plastic trough. After 5 min, 1 ml of prewarmed hybridization solution
(2× SSC [1× SSC is 0.15 M NaCl plus 0.015 M sodium citrate], 50 mM
Tris-HCl [pH 7.5], 0.1% SDS) was added, and a LiPA strip was
submerged and incubated in a shaking water bath at 50 ± 0.5°C for 1 h. The strips were washed with 1 ml of 2× SSC-0.1% SDS
for 30 min at 50°C. Subsequently, the strips were rinsed three times in phosphate buffer, and conjugate (streptavidin-alkaline phosphatase) was added. After incubation at room temperature for 30 min, the strips
were rinsed again and 4-nitroblue tetrazolium chloride and
5-bromo-4-chloro-3-indolylphosphate substrate was added. Hybrids are
visible as purple probe lines. Interpretation of the hybridization patterns was performed visually.
| |
RESULTS |
vacA S region.
The sequence heterogeneity of the
vacA s and m regions in H. pylori
isolates obtained from different locations in Europe, North America,
South America, Oceania, and Asia was analyzed by PCR and direct
sequencing of the amplimers. A PCR amplimer of one of the expected
sizes (176 bp for s1 and 203 bp for s2) was generated from each of the
98 isolates, indicating the broad specificity of the primers. For
analysis of the s region, 78 PCR amplimers were sequenced, including 67 type s1 fragments and 11 type s2 fragments. Phylogenetic analysis
showed that the type s2 sequences form a homogeneous cluster (Fig.
1). There were no substantial differences
among type s2 sequences obtained from strains of different geographic
origins. Among type s1 sequences, three distinct subtypes were
clearly distinguished, corresponding to the previously described subtypes s1a, s1b (4), and a new subtype, designated
s1c. Type s1c shows consistent variation at several loci compared to
types s1a and s1b and can be considered a specific recombinant of s1a and s1b (Fig. 2). The deduced amino acid
sequences also revealed consistent differences among the three
different s1 subtypes (Fig. 3). We
confirm a previous report (4) that there are five amino acid
differences between subtypes s1a and s1b (i.e., Ala18Val, Val20Ala, Val24Ile, Ile26Ala/Ser, and Thr27Ile). Subtype s1c differs from subtype s1a at two positions (Ala22Leu and Gln30Lys) and from s1b at seven positions (Ala18Val, Val20Ala, Ala22Leu, Ile24Val, Ala/Ser26Ile, Ile27Thr, and Glu/Gln30Lys). s1c strains
contain two specific amino acids (Leu22 and Lys30) not found in
other strains of the other subtypes and were isolated almost
exclusively from persons from East Asia (Fig. 1). Within the s1a and
s1b subtypes, there was no correlation with the geographic origins of
the H. pylori isolates.
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FIG. 1.
Phylogenetic tree of vacA s-region nucleotide
sequences, including two reference sequences (U07145 and U29401).
Clusters of subtypes s1a, s1b, s1c, and s2 are indicated. The sequence
from PE9012, containing recombinant s1a-s1b sequences, is underlined.
Letters in the names of the isolates indicate the country or location
of origin: Australia (AU), Costa Rica (CR), China (CH), Hong Kong (HK),
Japan (JA), The Netherlands (NL), New Zealand (NZ), Peru (PE), Portugal
(PO), Thailand (TH), and the United States (US). A reference bar is
shown for molecular distance.
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FIG. 2.
Alignment of partial nucleotide sequences of the
vacA s region, showing differences between s2, s1a, s1b, and
s1c subtypes. The recombinant s1a-s1b sequence from PE9012 is also
shown. Each of the 100-bp sequences presented here starts at position
36 of the vacA open reading frame. To permit alignment
between type s1 and s2 sequences, a dot indicates the absence of a
nucleotide in the s1 variants. Identical nucleotides are indicated by a
hyphen.
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FIG. 3.
Alignment of partial amino acid sequences of the
vacA s region. Consistent differences between s1a, s1b, and
s1c subtypes are indicated in boldface. To obtain proper alignment
between type s1 and s2 sequences, a dot indicates the absence of
an amino acid in s1 variants. Identical amino acids are indicated
by a hyphen. The sequences U07145 and U29401 are also presented as
references for s1a and s2, respectively.
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Pairwise comparisons of all sequences showed that the nucleotide
sequences within each subtype are more than 95% conserved.
Transitions were more frequent than transversions, and the majority
of
nucleotide substitutions were synonymous. The deduced amino
acid
sequences of all subtypes are more than 94% conserved (Table
3). The
vacA s region sequence
from PE9012 is located at an intermediate
branch in the phylogenetic
tree between the s1a and s1b clusters
(Fig.
1) and can be considered a
recombinant of s1a and s1b (Fig.
2). The PCR product from PE9012
hybridized strongly to probe P2s1b
but very weakly to probe P1s1b (data
not shown), and this result
is in complete agreement with the sequence
analysis results.
vacA m region.
For analysis of the m region, 82 PCR amplimers, including 38 type m1 fragments and 44 type m2 fragments,
comprising 288 and 362 bp, respectively, were examined by sequence
analysis. Phylogenetic analysis (Fig. 4)
indicated a clear separation between m1 and m2 sequences (sequence
distances, as calculated with DNADIST by the Kimura two-parameter
method, were 0.333 ± 0.026), largely because the m2 sequences
contain an additional 75 nucleotides that are not present in m1
sequences. The sizes of the amplimers of two isolates from Hong Kong
(isolates HK41 and HK46) and one isolate from China (isolate CH4) were
the same as those for other m2 strains, but the amplimers differed
markedly from those of other m2 sequences, as shown by their position
on a separate branch. Molecular distances between the 362-bp nucleotide
sequences from these three isolates and the other 41 m2 sequences were
0.198 ± 0.012, whereas among the latter group the distances
were only 0.036 ± 0.017. Since these sequence distance
distributions were not overlapping, the three sequences were classified
into a separate subtype, designated m2b. All other m2 sequences were
named m2a. The three m2b strains had been typed s1c. Within the m2a
cluster, there was no apparent association with the geographic
origins of the strains.
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FIG. 4.
Phylogenetic tree of vacA m-region sequences,
including four reference sequences (U05676, U05677, U07145, and
U29401). Clusters of type m1 and subtype m2a and m2b are indicated. The
origins of the isolates are defined in the legend to Fig. 1.
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Within the group of 38 type m1 sequences, sequence distances were
0.059 ± 0.031. The sequences obtained from nine Hong Kong
isolates and two Japanese isolates formed a separate phylogenetic
cluster, with sequence distances of 0.018 ± 0.009, suggesting
the
presence of specific m1 variation in these isolates (data
for only
seven isolates are presented in Fig.
4). However, the
molecular
distances between these 11 sequences and the remaining
27 m1 sequences
were only 0.090 ± 0.012. Since the sequence distance
distributions are overlapping, the sequence variation is not sufficient
to warrant the definition of two separate subtypes within m1.
Pairwise
comparisons of all sequences showed that the nucleotide
sequences
within each subtype are more than 95% conserved. Transitions
were more
frequent than transversions, and the majority of nucleotide
substitutions were synonymous. The deduced amino acid sequences
are
more than 91% conserved (Table
4).
On the basis of the sequence data generated, a set of general PCR
primers was developed for universal amplification of the
m region. To
ensure amplification from all m-region variants,
a mix of four
forward primers (primers VAMF1.1 to VAMF1.4) was
used (Table
1).
The target sequence for the reverse primer MR1
appeared to be highly
conserved. These PCR primers allowed specific
amplification of m-region
sequences from all 98 investigated isolates.
Reverse hybridization.
To develop a rapid, sensitive, and
specific method that could be used for the genotyping of
H. pylori strains for clinical purposes, we used
the sequence data to design a reverse hybridization LiPA.
Oligonucleotide probes specific for s1a, s1b, s1c, m1, m2a, and m2b (as
indicated in Table 2) were deduced from the sequences of the s and m
regions. All probes were individually optimized to obtain a high degree
of specificity under the defined reverse hybridization conditions.
Initial studies used well-characterized strains, and there was
agreement between LiPA and genotyping data (Fig.
5). The results of subsequent genotyping
based on the hybridization patterns of the LiPA were completely
concordant with the results of genotyping based on sequence analysis of
the vacA s region (78 strains) and m region (82 strains).
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FIG. 5.
Use of the reverse hybridization LiPA to determine the
vacA and cagA genotypes of H. pylori strains whose sequences were known. The strains
(genotypes) are as follows: AU10 (s1a, m1, cagA positive),
PO12 (s1b, m1, cagA positive), HK44 (s1c, m1,
cagA positive), PO24 (s2, m2a, cagA negative),
and HK46 (s1c, m2b, cagA positive). The positions of the
specific probes, as listed in Table 2, are indicated.
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| |
DISCUSSION |
Knowledge of the existence of different H. pylori genotypes may become clinically important since strains
containing cagA are more likely to cause more severe disease
than strains that lack cagA (7, 15, 33), type s1
vacA strains are more often associated with disease
than type s2 strains (3, 5), and responses to
anti-Helicobacter therapy also may vary for strains of
different genotypes (42). Similarly, adhesion of
H. pylori to the human gastric epithelium,
mediated by histo-blood group antigens, also appeared to be related to
distinct allelic variants of the bacterial babA gene
(19).
Although H. pylori is cosmopolitan, with
prevalences ranging from approximately 30% in developed countries to
more than 80% in the developing world, little is known about the
geographic distributions of specific H. pylori
strains (26, 29, 34). Differences in the prevalence of
particular H. pylori genotypes could play a role in
the incidence of H. pylori-associated diseases in
certain localities.
Analysis of H. pylori isolates from diverse
geographic locations permitted a comprehensive description of the s and
m regions of vacA. The recognition of two main s-region
types, s1 and s2, with both the size and amino acid sequences of
isolates from around the world being highly conserved, confirmed the
findings of Atherton et al. (4), who studied U.S. isolates
only. However, in addition to the s1a and s1b subtypes identified
previously, a third subtype (subtype s1c) was defined in the present
study. In a study based on subtype-specific PCR without hybridization
or sequence analysis, Ito et al. (20) found that s1a was the
predominant type in Japan. Our present data indicate that PCR analysis
with primers specific for subtypes s1a and s1b, as described earlier
(4), would identify all s1c isolates as subtype
s1a. The present study, as well as a more extensive study of a
worldwide collection of strains (data not shown), indicates that s1c is
the most prevalent subtype in isolates from East Asia.
Interestingly, the one Dutch patient colonized with an s1c
H. pylori strain (as determined by LiPA) had a
Chinese mother and was born in Indonesia. Whether s1c strains are
phenotypically different from s1a and s1b strains remains to be
determined.
Despite the very high overall genetic heterogeneity of H. pylori (18), the distinct s- and m-region variants
of vacA appear to be well conserved (>95% at the
nucleotide level), consistent with the functional constraints of the
encoded cytotoxin. The nucleotide substitution rates (transitions to
transversions and nonsynonymous to synonymous substitution rates)
observed in the s region indicate a high degree of sequence
conservation, as would be expected for a signal sequence. Subtype
s1c sequences were especially highly conserved. The
selective pressure in the m region appears to be less than that
in the s region, as shown by higher nonsynonymous to synonymous
substitution rates. The substitution rates of m1 and m2 variants were
very similar. On the basis of phylogenetic analyses, the number of
recombinants between the distinct subtypes appears to be limited.
However, PCR products were not cloned but were directly sequenced.
Therefore, it is also possible that the recombinant s1a-s1b sequence
represents consensus sequences of PCR products from mixed strains.
Although type s2 strains produce little or no active cytotoxin in vitro (4, 16), phylogenetic analysis revealed that type s2
sequences are as closely related to one another as sequences from the
toxin-producing type s1 strains. This observation suggests the
existence of selective pressure on type s2 alleles as well, implying
that the s2 gene product has a functional role in vivo.
Among the m-region sequences, both type m1 and m2 sequences were well
conserved. There was no obvious association between sequence variants
and the geographic origins of the isolates. Although type m1 sequences
from East Asian isolates differed from that of the main m1 variant,
this difference was insufficient to permit molecular classification as
a separate subtype. Although the amplimer size for the distinct m2
variant (m2b) found in three East Asian isolates was the same as that
for m2a, subtype m2b represents a separate branch in the phylogenetic
tree and can be clearly distinguished from subtype m2a.
Earlier PCR analysis of vacA (4) focused on a
more downstream m region. Several isolates from Japan failed to yield a
PCR product when the original m-region primers were used
(24), suggesting sequence heterogeneity in this part of
vacA. The fact that the novel m-region primers used in this
study, as deduced from the alignment of 86 sequences, permitted
efficient amplification of m-region sequences from all tested strains
indicates their broad applicability for analysis of H. pylori isolates from various geographic locations.
The PCR-reverse hybridization method reported here offers a tool
for epidemiological and clinical studies and permits the rapid
identification of the various vacA allelic types and the detection of cagA. Hybridization analysis is more reliable
than visual inspection of PCR products on agarose gels and is
required to specifically discriminate among defined subtypes. PCR
can be performed not only with cultured isolates but also
directly with gastric biopsy specimens (41), circumventing
expensive and time-consuming culture procedures. Some biopsy
specimens contain multiple strains (21, 35), and the
reverse hybridization assay is a very sensitive method for the
simultaneous detection of multiple genotypes.
In conclusion, analysis of a worldwide collection of H. pylori strains showed that the distinct vacA
alleles are well conserved. Extension of previous analyses revealed
that substantial s- and m-region heterogeneity exists, particularly
among strains from East Asia. Further subtyping of H. pylori strains by these methods should facilitate insights
into the evolution, epidemiology, and clinical importance of these
organisms.
| |
ACKNOWLEDGMENTS |
C. Figueiredo is supported by PRAXIS XXI (project
1/2.1/SAU/1356/95). This work was supported in part by grant R01 DK
53707 from the National Institutes of Health.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Delft Diagnostic
Laboratory, R. de Graafweg 7, 2625 AD, Delft, The Netherlands. Phone: 31-15-2604577. Fax: 31-15-2604550. E-mail:
L.J.van.Doorn{at}ddl.nl.
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REFERENCES |
| 1.
|
Akopyants, N. S.,
T. U. Bukanov,
T. U. Westblom,
S. Kresovich, and D. E. Berg.
1992.
DNA diversity among clinical isolates of Helicobacter pylori detected by PCR-based RAPD profile.
Nucleic Acids Res.
20:S137-S142.
|
| 2.
|
Akopyants, N. S.,
S. W. Clifton,
D. Kersulyte,
J. E. Crabtree,
B. E. Youree,
C. A. Reece,
N. O. Bukanov,
E. S. Drazek,
B. A. Roe, and D. E. Berg.
1998.
Analyses of the cag pathogenicity island of Helicobacter pylori.
Mol. Microbiol.
28:37-54[Medline].
|
| 3.
|
Atherton, J. C.
1997.
The clinical relevance of strain types of Helicobacter pylori.
Gut
40:701-703[Free Full Text].
|
| 4.
|
Atherton, J. C.,
P. Cao,
R. M. J. Peek,
M. K. Tummuru,
M. J. Blaser, and T. L. Cover.
1995.
Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration.
J. Biol. Chem.
270:17771-17777[Abstract/Free Full Text].
|
| 5.
|
Atherton, J. C.,
R. M. J. Peek,
K. T. Tham,
T. L. Cover, and M. J. Blaser.
1997.
Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori.
Gastroenterology
112:92-99[Medline].
|
| 6.
|
Beales, I. L.,
J. E. Crabtree,
D. Scunes,
A. Covacci, and J. Calam.
1996.
Antibodies to cagA protein are associated with gastric atrophy in Helicobacter pylori infection.
Eur. J. Gastroenterol. Hepatol.
8:645-649[Medline].
|
| 7.
|
Blaser, M. J.
1995.
Intrastrain differences in Helicobacter pylori: a key question in mucosal damage?
Ann. Med.
27:559-563[Medline].
|
| 8.
| Blaser, M. J. 1996. Role of vacA
and the cagA locus of Helicobacter pylori in
human disease. Aliment. Pharmacol. Ther. 10(Suppl.
1):73-77.
|
| 9.
|
Blaser, M. J.
1997.
Ecology of Helicobacter pylori in the human stomach.
J. Clin. Invest.
100:759-762[Medline].
|
| 10.
|
Bukanov, N. O., and D. E. Berg.
1994.
Ordered cosmid library and high-resolution physical-genetic map of Helicobacter pylori strain NCTC11638.
Mol. Microbiol.
11:509-523[Medline].
|
| 11.
|
Censini, S.,
C. Lange,
Z. Xiang,
J. E. Crabtree,
P. Ghiara,
M. Borodovsky,
R. Rappuoli, and A. Covacci.
1996.
cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors.
Proc. Natl. Acad. Sci. USA
93:14648-14653[Abstract/Free Full Text].
|
| 12.
|
Covacci, A.,
S. Censini,
M. Bugnoli,
R. Petracca,
D. Burroni,
G. Macchia,
A. Massone,
E. Papini,
Z. Xiang, and N. Figura.
1993.
Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer.
Proc. Natl. Acad. Sci. USA
90:5791-5795[Abstract/Free Full Text].
|
| 13.
|
Cover, T. L.
1996.
The vacuolating cytotoxin of Helicobacter pylori.
Mol. Microbiol.
20:241-246[Medline].
|
| 14.
|
Cover, T. L., and M. J. Blaser.
1992.
Purification and characterization of the vacuolating toxin from Helicobacter pylori.
J. Biol. Chem.
267:10570-10575[Abstract/Free Full Text].
|
| 15.
|
Cover, T. L.,
Y. Glupczynski,
A. P. Lage,
A. Burette,
M. K. Tummuru,
G. I. Perez-Perez, and M. J. Blaser.
1995.
Serologic detection of infection with cagA+ Helicobacter pylori strains.
J. Clin. Microbiol.
33:1496-1500[Abstract].
|
| 16.
|
Cover, T. L.,
M. K. Tummuru,
P. Cao,
S. A. Thompson, and M. J. Blaser.
1994.
Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains.
J. Biol. Chem.
269:10566-10573[Abstract/Free Full Text].
|
| 17.
|
Felsenstein, J.
1993.
PHYLIP, Phylogeny Inference Package, version 3.5c (computer program). J. Felsenstein
University of Washington, Seattle. (Distributed by the author.).
|
| 18.
|
Go, M. F.,
V. Kapur,
D. Y. Graham, and J. M. Musser.
1996.
Population genetic analysis of Helicobacter pylori by multilocus enzyme electrophoresis: extensive allelic diversity and recombinational population structure.
J. Bacteriol.
178:3934-3938[Abstract/Free Full Text].
|
| 19.
|
Ilver, D.,
A. Arnqvist,
J. Ogren,
I. M. Frick,
D. Kersulyte,
E. T. Incecik,
D. E. Berg,
A. Covacci,
L. Engstrand, and T. Boren.
1998.
Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging.
Science
279:373-377[Abstract/Free Full Text].
|
| 20.
|
Ito, Y.,
T. Azuma,
S. Ito,
H. Miyaji,
M. Hirai,
Y. Yamazaki,
F. Sato,
T. Kato,
Y. Kohli, and M. Kuriyama.
1997.
Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan.
J. Clin. Microbiol.
35:1710-1714[Abstract].
|
| 21.
|
Jorgensen, M.,
G. Daskalopoulos,
V. Warburton,
H. M. Mitchell, and S. L. Hazell.
1996.
Multiple strain colonization and metronidazole resistance in Helicobacter pylori-infected patients: identification from sequential and multiple biopsy specimens.
J. Infect. Dis.
174:631-635[Medline].
|
| 22.
|
Kuipers, E. J.,
G. I. Perez-Perez,
S. G. Meuwissen, and M. J. Blaser.
1995.
Helicobacter pylori and atrophic gastritis: importance of the cagA status.
J. Natl. Cancer Inst.
87:1777-1780[Abstract/Free Full Text].
|
| 23.
|
Leunk, R. D.,
P. T. Johnson,
B. S. David,
W. G. Kraft, and D. R. Morgan.
1988.
Cytotoxic activity in broth culture filtrates of Campylobacter pylori.
J. Med. Microbiol.
26:93-99[Abstract/Free Full Text].
|
| 24.
|
Maeda, S.,
K. Ogura,
M. Ishitobi,
F. Kanai,
H. Yoshida,
S. Ota,
Y. Shiratory, and M. Omata.
1996.
Diversity of Helicobacter pylori vacA gene in Japanese strains high activity type s1 is dominant in Japan.
Gastroenterology
100:A182.
|
| 25.
|
Marshall, D. G.,
D. C. Coleman,
D. J. Sullivan,
H. Xia,
C. A. O'Morain, and C. J. Smyth.
1996.
Genomic DNA fingerprinting of clinical isolates of Helicobacter pylori using short oligonucleotide probes containing repetitive sequences.
J. Appl. Bacteriol.
81:509-517[Medline].
|
| 26.
|
Miehlke, S.,
K. Kibler,
J. G. Kim,
N. Figura,
S. M. Small,
D. Y. Graham, and M. F. Go.
1996.
Allelic variation in the cagA gene of Helicobacter pylori obtained from Korea compared to the United States.
Am. J. Gastroenterol.
91:1322-1325[Medline].
|
| 27.
|
Peek, R. M.,
G. G. Miller,
K. T. Tham,
G. Perez-Perez,
X. Zhao,
J. C. Atherton, and M. J. Blaser.
1995.
Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains.
Lab. Invest.
73:760-770[Medline].
|
| 28.
|
Phadnis, S. H.,
D. Ilver,
L. Janzon,
S. Normark, and T. U. Westblom.
1994.
Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori.
Infect. Immun.
62:1557-1565[Abstract/Free Full Text].
|
| 29.
|
Schlemper, R. J.,
S. D. van der Werf,
J. P. Vandenbroucke,
I. Biemond, and C. B. Lamers.
1996.
Risk factors of peptic ulcer disease: difference impact of Helicobacter pylori in Dutch and Japanese populations?
J. Gastroenterol. Hepatol.
11:825-831[Medline].
|
| 30.
|
Schmitt, W., and R. Haas.
1994.
Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein.
Mol. Microbiol.
12:307-319[Medline].
|
| 31.
|
Simmonds, P.,
E. C. Holmes,
T. A. Cha,
S. W. Chan,
F. McOmish,
B. Irvine,
E. Beall,
P. L. Yap,
J. Kolberg, and M. S. Urdea.
1993.
Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region.
J. Gen. Virol.
74:2391-2399[Abstract/Free Full Text].
|
| 32.
|
Stuyver, L.,
R. Rossau,
A. Wyseur,
M. Duhamel,
B. Vandenborght,
H. van Heuverswyn, and G. Maertens.
1993.
Typing of HCV isolates and characterization of new (sub)types using a line probe assay.
J. Gen. Virol.
74:1093-1102[Abstract/Free Full Text].
|
| 33.
|
Takata, T.,
S. Fujimoto,
K. Anzai,
T. Shirotani,
M. Okada,
Y. Sawae, and J. Ono.
1998.
Analysis of the expression of cagA and vacA and the vacuolating activity in 167 isolates from patients with either peptic ulcers or non-ulcer dyspepsia.
Am. J. Gastroenterol.
93:30-34[Medline].
|
| 34.
|
Talley, N. J., and H. Xia.
1996.
Ethnicity as a risk factor for Helicobacter pylori infection and gastric cancer: environment, genetics, or both?
Aust. N. Z. J. Med.
26:628-631[Medline].
|
| 35.
|
Taylor, N. S.,
J. G. Fox,
N. S. Akopyantz,
D. E. Berg,
N. Thompson,
B. Shames,
L. Yan,
E. Fontham,
F. Janney,
F. M. Hunter, and P. Correa.
1995.
Long-term colonization with single and multiple strains of Helicobacter pylori assessed by DNA fingerprinting.
J. Clin. Microbiol.
33:918-923[Abstract].
|
| 36.
|
Telford, J. L.,
P. Ghiara,
M. Dell'Orco,
M. Comanducci,
D. Burroni,
M. Bugnoli,
M. F. Tecce,
S. Censini,
A. Covacci, and Z. Xiang.
1994.
Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease.
J. Exp. Med.
179:1653-1658[Abstract/Free Full Text].
|
| 37.
|
Tummuru, M. K.,
T. L. Cover, and M. J. Blaser.
1993.
Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production.
Infect. Immun.
61:1799-1809[Abstract/Free Full Text].
|
| 38.
|
Tummuru, M. K.,
S. A. Sharma, and M. J. Blaser.
1995.
Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells.
Mol. Microbiol.
18:867-876[Medline].
|
| 39.
|
Van de Peer, Y., and R. De Wachter.
1994.
TREECON for Windows: a software package for the construction and drawing of evolutionary trees for the Microsoft Windows environment.
Comput. Appl. Biosci.
10:569-570[Free Full Text].
|
| 40.
|
van der Ende, A.,
E. A. Rauws,
M. Feller,
C. J. Mulder,
G. N. Tytgat, and J. Dankert.
1996.
Heterogeneous Helicobacter pylori isolates from members of a family with a history of peptic ulcer disease.
Gastroenterology
111:638-647[Medline].
|
| 41.
| van Doorn, L. J. Unpublished observations.
|
| 42.
|
van Doorn, L. J.,
W. G. V. Quint,
P. M. Schneeberger,
G. N. J. Tytgat, and W. A. de Boer.
1997.
Association between vacA and cagA status of Helicobacter pylori and the efficacy of a 1-day quadruple therapy.
Lancet
350:71-72[Medline].
|
| 43.
|
Xiang, Z.,
S. Censini,
P. F. Bayeli,
J. L. Telford,
N. Figura,
R. Rappuoli, and A. Covacci.
1995.
Analysis of expression of cagA and vacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that cagA is not necessary for expression of the vacuolating cytotoxin.
Infect. Immun.
63:94-98[Abstract].
|
Journal of Clinical Microbiology, September 1998, p. 2597-2603, Vol. 36, No. 9
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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-
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-
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-
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[Full Text]
-
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[Abstract]
[Full Text]
-
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37: 2979-2982
[Abstract]
[Full Text]
-
Marais, A., Mendz, G. L., Hazell, S. L., Megraud, F.
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63: 642-674
[Abstract]
[Full Text]
-
Doig, P., de Jonge, B. L., Alm, R. A., Brown, E. D., Uria-Nickelsen, M., Noonan, B., Mills, S. D., Tummino, P., Carmel, G., Guild, B. C., Moir, D. T., Vovis, G. F., Trust, T. J.
(1999). Helicobacter pylori Physiology Predicted from Genomic Comparison of Two Strains. Microbiol. Mol. Biol. Rev.
63: 675-707
[Abstract]
[Full Text]
-
Perez-Perez, G. I., Peek, R. M. Jr., Atherton, J. C., Blaser, M. J., Cover, T. L.
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6: 489-493
[Abstract]
[Full Text]
-
van Doorn, L.-J., Debets-Ossenkopp, Y. J., Marais, A., Sanna, R., Mégraud, F., Kusters, J. G., Quint, W. G. V.
(1999). Rapid Detection, by PCR and Reverse Hybridization, of Mutations in the Helicobacter pylori 23S rRNA Gene, Associated with Macrolide Resistance. Antimicrob. Agents Chemother.
43: 1779-1782
[Abstract]
[Full Text]
-
Yamaoka, Y., Kodama, T., Gutierrez, O., Kim, J. G., Kashima, K., Graham, D. Y.
(1999). Relationship between Helicobacter pylori iceA, cagA, and vacA Status and Clinical Outcome: Studies in Four Different Countries. J. Clin. Microbiol.
37: 2274-2279
[Abstract]
[Full Text]
-
van Doorn, L.-J., Figueiredo, C., Sanna, R., Blaser, M. J., Quint, W. G. V.
(1999). Distinct Variants of Helicobacter pylori cagA Are Associated with vacA Subtypes. J. Clin. Microbiol.
37: 2306-2311
[Abstract]
[Full Text]
-
van Doorn, N. E. M., Namavar, F., van Doorn, L.-J., Durrani, Z., Kuipers, E. J., Vandenbroucke-Grauls, C. M. J. E.
(1999). Analysis of vacA, cagA, and IS605 Genotypes and Those Determined by PCR Amplification of DNA between Repetitive Sequences of Helicobacter pylori Strains Isolated from Patients with Nonulcer Dyspepsia or Mucosa-Associated Lymphoid Tissue Lymphoma. J. Clin. Microbiol.
37: 2348-2349
[Abstract]
[Full Text]
-
van Doorn, N. E. M., Namavar, F., Sparrius, M., Stoof, J., van Rees, E. P., van Doorn, L.-J., Vandenbroucke-Grauls, C. M. J. E.
(1999). Helicobacter pylori-Associated Gastritis in Mice is Host and Strain Specific. Infect. Immun.
67: 3040-3046
[Abstract]
[Full Text]
-
van Doorn, L.-J., Verschuuren-van Haperen, A., Burnens, A., Huysmans, M., Vandamme, P., Giesendorf, B. A. J., Blaser, M. J., Quint, W. G. V.
(1999). Rapid Identification of Thermotolerant Campylobacter jejuni, Campylobacter coli, Campylobacter lari, and Campylobacter upsaliensis from Various Geographic Locations by a GTPase-Based PCR-Reverse Hybridization Assay. J. Clin. Microbiol.
37: 1790-1796
[Abstract]
[Full Text]
-
Ye, D., Willhite, D. C., Blanke, S. R.
(1999). Identification of the Minimal Intracellular Vacuolating Domain of the Helicobacter pylori Vacuolating Toxin. J. Biol. Chem.
274: 9277-9282
[Abstract]
[Full Text]
Top
Abstract
Introduction
