M J Blaser

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..coli strain and against Salmonella. Our data provide evidence of active competition for colonization niches in the C. elegans gut, as determined by bacterial factors and subject to in vivo selection...

..Tetranucleotide usage deviation (TUD) patterns were chosen since they have previously been shown to contain phylogenetic signal similar to that of 16S rRNA...

..A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia...

..In this study, we considered whether early-life family structure affects the risk of later developing gastric cancer among H. pylori+ men...

..The disappearance of H. pylori (especially cag+ strains), possibly contributing to the risk of these esophageal diseases, may be an indicator for changing human microecology...

..Lack of a parallel increase in oesophageal adenocarcinomas could be due to misclassification artefacts and/or coding preferences for gastro-oesophageal junction tumours...

..The model can aid prediction of equilibrium states in the context of further change: widespread immunodeficiency, changing population densities, or extinctions...

..Finally, our challenge for the future is to better understand the steps in microbe-induced cancers to optimize both prevention and therapy...

..pylori iceA1 strains reflects levels of iceA1 transcription in vivo...

..pylori infection are not related to HspA antigenicity or to sequence variation. However, B-domain sequence variation may be a marker for the study of the genetic diversity of H. pylori strains of different geographic origins...

..pylori strains and induction of particular serological responses are significantly associated with marked histological findings in the gastric cardia but not with adenocarcinoma of either the gastric cardia or esophagus...

..Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection...

..The data imply that the H. pylori dapE mutant may be useful as a conditionally lethal vaccine...

..E. coli expressing C. fetus sapA and sapCDEF secreted SapA, indicating that the sapCDEF genes are sufficient for SLP secretion. C. fetus SLPs therefore are transported to the cell surface by a type I secretion system...

..pylori pathogenesis. Consequently, the current studies were undertaken to characterize iceA1 transcription and to define the structure of iceA1-containing transcripts to evaluate the potential of this gene to encode functional proteins...

..This study aimed to determine whether H. pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma...

..The changes detected by RAPD-PCR and AFLP indicate that genetic drift occurs within H. pylori populations over the course of years of colonization of a single host...

..HUM PATHOL 32:264-273. This is a US Government work. There are no restrictions on its use...

..pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts...

..The specificity of colonization by Helicobacter pylori and complex host-bacterium interactions cannot be readily examined in humans. The aim of this study was to perform such analyses in rhesus monkeys...

..Thus, in the 21st century, the continuing decline in H. pylori may lead to the disappearance of duodenal ulcers and distal gastric cancers and toward a marked increase in GERD, Barrett's esophagus, and esophageal adenocarcinoma...

..The approach described should significantly enhance the ability to manipulate gene function in H. pylori and other organisms that have substantial restriction barriers to transformation...

..pylori populations use mutation and transformation to regulate gene function...

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..Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates...

..We conclude that hpyIM encodes a DNA methyltransferase, M.HpyI, that is well conserved among diverse H. pylori strains and that modifies H. pylori genomes at CATG sites...

..pylori cells grown at pH 5 compared with pH 7, which suggests that H. pylori may alter its LPS structure in response to acidic pH. This may be an important adaptation facilitating H. pylori colonization of the acidic gastric environment...

..These results may explain heterogeneity in levels of gastric epithelial cell proliferation and apoptosis found within H. pyloricolonized mucosa...

..Geographic variation in the genetic characteristics of H. pylori strains may be a factor contributing to geographic variation in gastric cancer incidence...

..Similarly, adherence to AGS and KatoIII cells was unaffected by the mutations. Together, these findings indicate that Le expression is not necessary for mouse gastric colonization or for H. pylori adherence to epithelial cells...

..Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization...

..This novel family of hypervariable genes with conserved, repetitive, and allelic domains may represent an important locus for understanding H. pylori persistence in its natural host...

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..In this study, we determined whether the proportion of subjects colonised by cagA(+) or cagA(-) H pylori strains has changed as the overall prevalence of H pylori(+) has declined...

..Analysis of HP0638 CT polymorphisms may serve as a new typing system to discriminate H. pylori isolates for epidemiological purposes...

..8%) and hisJ (28.9%), whereas ORF C has nearly 50% identity to glnQ and hisP. Thus, PEB1 could be involved both in binding to intestinal cells and in amino acid transport...

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..These results demonstrate the high prevalence of mixed colonization and indicate that the H. pylori East Asian vacA genotype has survived in all three populations tested...

..Although a direct function for hrgA in virulence could not be demonstrated, our data indicate that hrgA is a strain-specific gene that might be associated with gastric cancer among H. pylori isolates from Asian patients...

..Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response...

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..These findings indicate that within an individual host, intragenomic recombination between H. pylori repetitive DNA produces strain variants differing in their signals to host cells...

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..pylori strains...

..As divergent SLP C-termini possess multiple antigenic sites, their reciprocal recombination behind the unique sap promoter leads to continuing antigenic variation...

..In addition to establishing a collection of H. pylori isolates from a remote area in the world, we show that use of H. pylori whole-cell and Cag A serology together increases the sensitivity for the detection of colonization...

..pylori and Helicobacter bilis) but not Escherichia coli suggests specificity based on DNA source. Finally, the cag island was determined to be unnecessary for high-frequency transformation...

..The sensitivity of H. pylori to DCCD at pH 7 and 6, and failure to recover F1F0 H. pylori mutants under similar conditions, suggests that the function of this enzyme is required for survival of H. pylori at these pHs...

..In total, the observed differences suggest that the sap island has evolved differing genotypes that are plastic, perhaps enabling colonization of varied niches, in addition to antigenic variation...

..pylori populations can change Lewis phenotypes during long-term colonization of natural hosts to resemble those of their hosts, providing evidence for host selection for bacterial phenotypes...

..pylori>H. influenzae) restored electro-transformation. Thus, C. jejuni expresses a DprA ortholog that functionally most closely resembles that of H. pylori and is involved in DNA transformation...

..Our findings indicate that H. pylori possesses phase-variable base excision repair, consistent with a tension between repair and mutation...

..Asthma, a serious health problem worldwide, is becoming more common. Colonization with Helicobacter pylori, a major human indigenous (commensal) microbe, during early life may be relevant to the risk of childhood asthma...

..8% amino acid identity with the corresponding region from tox+ strain 60190. Thus, sequence divergence in vacA genes may explain the lack of functionally active cytotoxin production by some H. pylori isolates...

..Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis...

..In total, these data indicate that C. fetus can use multiple sites within the FCR for its sap-related DNA inversion...

..fetus genome, integral to its biology...

..001), whereas normal skin from the psoriatic patients showed intermediate levels (12.3+/-21.6%). We conclude that psoriasis is associated with substantial alteration in the composition and representation of the cutaneous bacterial biota...

..pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight...

..To identify the bacterial flora in conditions such as Barrettos esophagus and reflux esophagitis to determine if they are similar to normal esophageal flora...

..These studies indicate that H. pylori evolves to resemble the host's gastric Le phenotype, and reveal a bacterial genetic locus that is subject to host-driven selection pressure...

..These findings indicate that H. pylori-specific antibody responses are host-specific with IgG1:IgG4 ratios stable over 21 years, IgG1 responses predominating, and HspA seroconversion with aging...

..Taken together, these observations support a system of highly efficient short-fragment recombination involving multiple recombination events within a single locus...

..pylori that face high-level genotoxic stress in vivo...

..Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma...

..These studies provide a new paradigm for adaptation under increased selective pressures that may be present in other prokaryotes...

..Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach...

..jejuni and that nitric oxide and reactive nitrogen species comprise part of the innate defense mechanisms that contribute to the resolution of C. jejuni infection...

..These data indicate H. pylori effects on host epithelial MMP-1 expression via ERK, with p38 playing a potential regulatory role...

..pylori population biology...

..4% of all clones. These results show that the bacterial biota in normal superficial skin is highly diverse, with few well conserved and well represented genera, but otherwise low-level interpersonal consensus...

..These findings provide evidence for a complex but conserved bacterial population in the normal distal esophagus...

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..pylori infection and/or cyclooxygenase inhibition may induce epithelial cell signaling to contribute to gastric ulcerogenesis...

..This phenotypic analysis is consistent with the phylogenetic and biochemical data suggesting that MutS1 and MutS2 have divergent functions...

..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...

..These data suggest that use of QS inhibitors could represent novel therapies for anthrax...

..pylori RecG resolvase provides an "antirepair" pathway allowing for selection of varied strains. Such competition between repair and antirepair provides a novel mechanism to maximize fitness at a bacterial population level...

..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...

..Inactivation of HP0638 does not alter epithelial responses mediated by the cag island in vitro. Assessment of apoptosis in vitro identified a group of H. pylori isolates that induce more severe gastric inflammation and atrophy...

..pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies...

..Therefore, host context appears critical in defining the function of recG. The fact that in E. coli recG phenotypes are not constant in other species indicates the diverse roles for conserved recombination genes in prokaryotic evolution...

..pylori groups. In this US population-based study, there was no significant association between H. pylori colonization, cagA+ strains of H. pylori, and being overweight...

..pylori R-M diversity limits acquisition of chromosomal DNA fragments of >/=1 kb...

..pylori. That these events are recA-dependent and DNase-resistant indicates their likely cause is intragenomic recombination...

..jejuni and all 15 C. coli strains but none of the isolates of the other three bacterial species. The PEB1 and PEB3 proteins appear to be candidate antigens for both a Campylobacter vaccine and for serological assays for the pathogen...

..In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer...

..tuberculosis were negative for IS6110. We provide evidence that one of a variety of Mycobacterium species, especially organisms resembling M. tuberculosis, is found in most patients with sarcoidosis...

..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...

..Le(y) synthesis was restored and Le(x) expression was reciprocally lowered. From these studies, we confirmed the principal role of futC slipped-strand mispairing in Le antigenic variation in vitro and in vivo...

..jejuni strains were overrepresented among GBS-associated strains in the United States and Germany and were significantly more serum-resistant than non-O:19 strains. The mechanism of this resistance appears unrelated to C3 binding...

..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...

..Including mathematical analyses in these studies also permits a generalization of the principles and their applications to other microbes involved in human health and disease. ..

..Including mathematical analyses in these studies also permits a generalization of the principles and their applications to other microbes involved in human health and disease. ..

..The experimental results will enable development of deterministic models relating genotypic and phenotypic variation with selection. ..

..In initial studies, spores will be given subcutaneosly. Efficacy parameters will be defined as above. Successful trials can lead to phase I studies in humans, and treatment studies in non-human primates. ..

..Finally, the data generated can be used to develop a mathematical model of antigenic variation that focuses on the relationship between microbial recombination generating diversity and host selection determining the direction of change. ..

..3) To examine the effect of recombination between two different H.pylori strains during experimental infections, and to develop representative mathematical models for this more complex phenomenon. ..

..pylori infections. ..

..We will focus on both maternal and antibiotic effects on the composition of the gastric and colonic bacterial populations, and their metabolic effects. ..