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Martin J Blaser

Publications and source records attributed to Martin J Blaser.

At least 73 records · Page 4Linked to original sources
PubMed2003

Use of an open-reading frame-specific Campylobacter jejuni DNA microarray as a new genotyping tool for studying epidemiologically related isolates.

Findings from use of an open-reading frame-specific Campylobacter jejuni DNA microarray to investigate genetic diversity among clinical isolates associated with 5 independent clusters of infection were compared with data from random amplified polymeric DNA (RAPD) and Penner serotyping analyses. The DNA microarray provides a highly specific epidemiological typing tool for analysis of C. jejuni isolates and reveals both divergent and highly conserved gene classes among isolates.

Animals↗
PubMed2003

Helicobacter pylori and TT virus prevalence in Japanese children.

BACKGROUND: The major transmission route of Helicobacter pylori, oral-oral or fecal-oral, remains to be established. TT virus (TTV), a recently discovered microbe that is prevalent in healthy persons, is believed to be mainly transmitted by nonparenteral routes. The purpose of this study was to test the hypothesis that these two microorganisms have a common mode of transmission. METHODS: We investigated the seroprevalence of H. pylori and TTV in a cross-sectional study of 454 healthy Japanese children from birth to age 15 years, living in five different geographic areas. Determination of H. pylori status was based on the presence of specific serum IgG and IgA antibodies, determined using enzyme immunoassays. TTV DNA was detected and the titer was determined using semiquantitative polymerase chain reaction with heminested primers. RESULTS: The overall prevalences of H. pylori and TTV were 12.2% and 21.6%, respectively. An age-related increase of prevalence was shown for H. pylori ( P < 0.001), but not for TTV ( P = 0.23). Titers of TTV DNA significantly decreased with age (P = 0.02). There were significant geographic differences in TTV prevalence ( P < 0.001), but not in H. pylori seroprevalence (P = 0.33). There was no true correlation between the prevalence of these two organisms (Phi coefficient = -0.02 and P = 0.66). CONCLUSIONS: Although Japanese children frequently acquire both H. pylori and TTV, especially in early childhood, their acquisition appears to be independent.

Adolescent↗
PubMed2003

Structure and genotypic plasticity of the Campylobacter fetus sap locus.

The Campylobacter fetus surface layer proteins (SLPs), encoded by five to nine sapA homologues, are major virulence factors. To characterize the sapA homologues further, a 65.9 kb C. fetus genomic region encompassing the sap locus from wild-type strain 23D was completely sequenced and analysed; 44 predicted open reading frames (ORFs) were recognized. The 53.8 kb sap locus contained eight complete and one partial sapA homologues, varying from 2769 to 3879 bp, sharing conserved 553-2622 bp 5' regions, with partial sharing of 5' and 3' non-coding regions. All eight sapA homologues were expressed in Escherichia coli as antigenic proteins and reattached to the surface of SLP- strain 23B, indicating their conserved function. Analysis of the sap homologues indicated three phylogenetic groups. Promoter-specific polymerase chain reactions (PCRs) and sapA homologue-specific reverse transcription (RT)-PCRs showed that the unique sapA promoter can potentially express all eight sapA homologues. Reciprocal DNA recombination based on the 5' conserved regions can involve each of the eight sapA homologues, with frequencies from 10(-1) to 10(-3). Intragenic recombination between sapA7 and sapAp8, mediated by their conserved regions with a 10(-1)-10(-2) frequency, allows the formation of new sap homologues. As divergent SLP C-termini possess multiple antigenic sites, their reciprocal recombination behind the unique sap promoter leads to continuing antigenic variation.

Animals↗
PubMed2003

Promoter analysis of Helicobacter pylori genes with enhanced expression at low pH.

To identify Helicobacter pylori genes with expression that is enhanced under low pH conditions, we used subtractive hybridization methodology. We identified 28 acid-induced genes, of which 18 have known or putative functions. Six pairs of genes were co-transcribed. Primer extension analysis identified single or multiple transcriptional start points (tsp) for 14 of the 22 loci. Sequence analysis of the -10 regions upstream of the tsps revealed consensus motifs for multiple RNA polymerase sigma factors present in H. pylori (sigma80, sigma54 and sigma28). No sequences resembling the -35 Escherichia coli consensus sequence (TTGACA) were present upstream of any of the genes. Both increased gene transcription and decreased mRNA decay contribute to the observed increase in H. pylori transcript abundance at acid pH. These studies document the complex response of H. pylori to environmental pH changes, and provide insight into mechanisms used for intragastric survival.

Bacterial Proteins↗
PubMed2003

Tooth loss, pancreatic cancer, and Helicobacter pylori.

BACKGROUND: Poor dental health has been associated with increased risks of oral, esophageal, and gastric cancer and may also be associated with pancreatic cancer. In addition, Helicobacter pylori has been found in dental plaque and has been associated with periodontal disease and pancreatic cancer. OBJECTIVE: The objective was to investigate prospectively the relation between dentition history and pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort in Finland and the association between dentition history and H. pylori seropositivity in a cross-sectional sample of subjects without cancer (n = 475) from the same cohort. DESIGN: Of the 29,104 male smokers aged 50-69 y in the cohort for whom there were complete data, 174 developed pancreatic cancer from 1985 to 1997. Cox proportional hazard models were used to estimate age-, smoking-, education-, urban living-, and height-adjusted hazard ratios and 95% CIs for pancreatic cancer, and logistic regression models were used to estimate age- and education-adjusted odds ratios for H. pylori carriage. RESULTS: Tooth loss was positively associated with pancreatic cancer (edentulous compared with missing 0-10 teeth: hazard ratio = 1.63; 95% CI: 1.09, 2.46; P for trend = 0.02) but was not significantly associated with H. pylori seropositivity (edentulous compared with missing 0-10 teeth: odds ratio = 1.30; 95% CI: 0.73, 2.32; P for trend = 0.37). CONCLUSION: Additional studies are needed to evaluate the association between tooth loss and pancreatic cancer, as well as cancers at other gastrointestinal sites, particularly with respect to possible biological mechanisms.

Aged↗
PubMed2003

Evolutionary implications of microbial genome tetranucleotide frequency biases.

We compared nucleotide usage pattern conservation for related prokaryotes by examining the representation of DNA tetranucleotide combinations in 27 representative microbial genomes. For each of the organisms studied, tetranucleotide usage departures from expectations (TUD) were shared between related organisms using both Markov chain analysis and a zero-order Markov method. Individual strains, multiple chromosomes, plasmids, and bacteriophages share TUDs within a species. TUDs varied between coding and noncoding DNA. Grouping prokaryotes based on TUD profiles resulted in relationships with important differences from those based on 16S rRNA phylogenies, which may reflect unequal rates of evolution of nucleotide usage patterns following divergence of particular organisms from a common ancestor. By both symmetrical tree distance and likelihood analysis, phylogenetic trees based on TUD profiles demonstrate a level of congruence with 16S rRNA trees similar to that of both RpoA and RecA trees. Congruence of these trees indicates that there exists phylogenetic signal in TUD patterns, most prominent in coding region DNA. Because relationships demonstrated in TUD-based analyses utilize whole genomes, they should be considered complementary to phylogenies based on single genetic elements, such as 16S rRNA.

Chromosome Mapping↗
PubMed2003

Detection of a luxS-signaling molecule in Bacillus anthracis.

Quorum-sensing regulation of density-dependent genes has been described for numerous bacterial species. The partially annotated genome sequence of Bacillus anthracis contains an open reading frame (BA5047) predicted to encode an ortholog of luxS, required for synthesis of the quorum-sensing signaling molecule autoinducer-2 (AI-2). To determine whether B. anthracis produces AI-2, the Vibrio harveyi luminescence bioassay was used. Cell-free conditioned media from vaccine (Sterne) strain 34F(2) induced luminescence in V. harveyi reporter strain BB170, indicating its production of AI-2. Cloned BA5047, expressed in Escherichia coli DH5 alpha cells, restored AI-2 activity to these cells. To evaluate whether BA5047 is essential for AI-2 synthesis, it was deleted through allelic exchange with marker rescue; the resulting mutant had no functional luxS activity and had reduced growth in vitro. In the wild-type strain, AI-2 activity was greatest during the exponential phase of growth. In total, these data indicate that BA5047 is a functional luxS ortholog in B. anthracis necessary for growth-phase-specific AI-2 expression. Thus, B. anthracis may utilize extracellular signaling molecules to regulate density-dependent gene expression.

Bacillus anthracis↗
PubMed2003

Transient and persistent Helicobacter pylori colonization in Native American children.

Helicobacter pylori is chiefly acquired in childhood, but the exact timing of acquisition is not well understood. The main goal of this study was to assess H. pylori acquisition in a pediatric population. We studied two cohorts of Native American children: a birth cohort of 50 children and 58 older children (mean age, 53 months). We measured serum immunoglobulin G (IgG), IgM, and IgA antibodies to H. pylori whole-cell antigen and IgG antibodies to CagA. Among 44 birth cohort children monitored for more than 12 months, 24 (54.5%) had seroconversions, 7 (15.9%) were transient, and 17 (38.6%) were persistent. Among the older children, 49 (84.5%) of the 58 children were monitored for 1 year; 34 (69.4%) had H. pylori antibodies at study entry. During the next year, 7 (20.6%) children seroreverted, and of 15 initially negative children, 5 (33.3%) seroconverted. In both groups, evaluation of CagA antibodies increased the sensitivity of H. pylori detection. Serum pepsinogen I (PGI) levels in H. pylori-negative children rose significantly until age 6 months and remained constant for the next 19 months. At the time of H. pylori seroconversion, PGI peaked to levels significantly higher than in the never-seroconverted (P = 0.02) and the pre-seroconverted (P = 0.03) children, but then declined to levels paralleling those of H. pylori-negative children. Thus, H. pylori acquisition, accompanied by a transient PGI increase, was frequent in this population, especially in the second and third years of life, but often was brief.

Adult↗
PubMed2003

An email alert system for internal medicine physicians.

This study evaluated the effectiveness of an email-based alerting system for internal medicine house staff and faculty in geographically dispersed locales. Responses to a test alert email message were used to quantify the rapidity by which physicians read the message, and to define subgroups in which this communication modality proved most successful. The results of this study are being used to improve our preparedness for emergencies.

Academic Medical Centers↗
PubMed2002

Helicobacter pylori interstrain restriction-modification diversity prevents genome subversion by chromosomal DNA from competing strains.

Helicobacter pylori, bacteria that colonize the human gastric mucosa, possess a large number of genes for restriction-modification (R-M) systems, and essentially, every strain possesses a unique complement of functional and partial R-M systems. Nearly half of the H.pylori strains studied possess an active type IIs R-M system, HpyII, with the recognition sequence GAAGA. Recombination between direct repeats that flank the R-M cassette allows for its deletion whereas strains lacking hpyIIRM can acquire this cassette through natural transformation. We asked whether strains lacking HpyII R-M activity can acquire an active hpyIIRM cassette [containing a 1.4 kb kanamycin resistance (aphA) marker], whether such acquisition is DNase sensitive or resistant and whether restriction barriers limit acquisition of chromosomal DNA. Our results indicate that natural transformation and conjugation-like mechanisms may contribute to the transfer of large (4.8 kb) insertions of chromosomal DNA between H.pylori strains, that inactive or partial R-M systems can be reactivated upon recombination with a functional allele, consistent with their being contingency genes, and that H.pylori R-M diversity limits acquisition of chromosomal DNA fragments of >/=1 kb.

DNA Methylation↗
PubMed2002

East Asian genotypes of Helicobacter pylori strains in Amerindians provide evidence for its ancient human carriage.

Phylogenies of indigenous microbes have been used as surrogates for the origins of the hosts that carry them. Conversely, polymorphisms may be used to date the spread of a microbial species when information about their host populations is available. Therefore, we examined polymorphisms in Helicobacter pylori, which persistently colonize the human stomach, to test the hypothesis that they have been ancient inhabitants of humans. Three H. pylori loci that previously have been shown to have phylogeographic affinity have been analyzed for two populations with different ethnic origins from Venezuela. In a group of Amerindian subjects from Amazonia, East Asian H. pylori genotypes were present for each of the loci examined but were absent in a mestizo population from Caracas. These findings provide evidence that H. pylori has been present in humans at least since ancestors of Amerindians migrated from Asia more than 11,000 years ago.

Africa South of the Sahara↗
PubMed2002

Helicobacter pylori CagA seropositivity and gastric carcinoma risk in a Japanese American population.

Helicobacter pylori colonization is associated with gastric cancer, but whether and to what extent the risk is greater for strains with the cagA gene than for those without needs to be determined. Between 1967 and 1977, 9963 Japanese American men were recruited and examined. By 1996, incident cases of gastric carcinoma of the distal stomach had been diagnosed in 261 men. Stored serum samples from these case patients and 261 age-matched control subjects were tested for immunoglobulin G antibodies to H. pylori and to the CagA product of H. pylori, using antibody-specific enzyme-linked immunosorbent assays. Compared with H. pylori-negative, CagA-negative men, H. pylori-positive, CagA-negative men had an odds ratio (OR) of 2.7 (95% confidence interval [CI], 1.3-5.6) for intestinal gastric carcinoma. Men seropositive for both H. pylori and CagA had an OR of 4.1 (95% CI, 2.2-7.7). This suggests that colonization by an H. pylori strain with the cagA gene is associated with a greater risk of intestinal gastric carcinoma.

Adult↗
PubMed2002

Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori.

iceA1 in Helicobacter pylori is a homolog of nlaIIIR, which encodes the CATG-specific restriction endonuclease NlaIII in Neisseria lactamica. Analysis of iceA1 sequences from 49 H.pylori strains shows that a full-length NlaIII-like ORF is present in 10 strains, including CH4, but in other strains, including strain 60190, the ORFs are truncated due to a variety of mutations. Our goal was to determine whether iceA1 can encode a NlaIII-like endonuclease. Overexpression in Escherichia coli of iceA1 from CH4, but not from 60190, yielded NlaIII-like activity, indicating that the full-length iceA1 is a functional endonuclease gene. Repair of the iceA1 frameshift mutation in strain 60190 and its expression in E.coli yielded functional NlaIII-like activity. We conclude that iceA1 in CH4 is a functional restriction endonuclease gene, while iceA1 in 60190 is not, due to a frameshift mutation, but that its repair restores its restriction endonuclease activity.

Amino Acid Sequence↗
PubMed2002

Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease.

Although colonization with any Helicobacter pylori strain is associated with peptic ulcer, it is uncertain whether the risk is greater with cagA(+) or cagA(-) strains, which differ in their biology. A nested case-control study was done, based on a cohort of 5,443 Japanese-American men examined on the Hawaiian island of Oahu from 1967 to 1970. A total of 150 men with gastric ulcer, 65 with duodenal ulcer, and 14 with both diseases were identified. The authors matched the 229 cases with 229 population controls and tested their serum for immunoglobulin G antibodies to H. pylori and immunoglobulin G antibodies to the cagA product of H. pylori using enzyme-linked immunosorbent assays. Persons with H. pylori positivity had an odds ratio of 4.0 (95% confidence interval (CI): 1.9, 8.5) for gastric ulcer and 2.5 (95% CI: 0.8, 7.4) for duodenal ulcer. For CagA positivity, the odds ratios were 1.4 (95% CI: 0.9, 2.4) for gastric ulcer and 2.6 (95% CI: 1.1, 5.8) for duodenal ulcer. Subjects who were seropositive for both H. pylori and CagA had an odds ratio of 4.4 (95% CI: 1.8, 10.5) for gastric ulcer and 5.8 (95% CI: 1.1, 30.0) for duodenal ulcer. The results suggest that colonization with a cag(+) H. pylori strain elevates the risk beyond that of a cag(-) H. pylori strain for both gastric and duodenal ulcers.

Antibodies, Bacterial↗
PubMed2002

Phenotypic and genotypic variation in methylases involved in type II restriction-modification systems in Helicobacter pylori.

To determine relationships between Helicobacter pylori geographical origin and type II methylase activity, we examined 122 strains from various locations around the world for methylase expression. Most geographic regions possessed at least one strain resistant to digestion by each of 14 restriction endonucleases studied. Across all of the strains studied, the average number of active methylases was 8.2 +/- 1.9 with no significant variation between the major geographic regions. Although seven pairs of isolates showed the same susceptibility patterns, their cagA/vacA status differed, and the remaining 108 strains each possessed unique patterns of susceptibility. From a single clonal group, 15 of 18 strains showed identical patterns of resistance, but diverged with respect to M.MboII activity. All of the methylases studied were present in all major human population groupings, suggesting that their horizontal acquisition pre-dated the separation of these populations. For the hpyV and hpyAIV restriction-modification systems, an in-depth analysis of genotype, indicating extensive diversity of cassette size and chromosomal locations regardless of the susceptibility phenotype, points toward substantial strain-specific selection involving these loci.

Antigens, Bacterial↗
PubMed2002

Mailborne transmission of anthrax: Modeling and implications.

A mathematical model is developed to analyze the transmission of inhalational anthrax through the postal system by cross-contamination of mail. The model consists of state vectors describing the numbers of cross-contaminated letters generated, the numbers of anthrax spores on these letters, the numbers of resulting infections in recipients, and matrices of transition probabilities acting on these vectors. The model simulates the recent outbreak in the United States, and provides a general framework to investigate the potential impact of possible future outbreaks.

Anthrax↗