scholarly journals Allelic Variation within Helicobacter pylori babA and babB

2001 ◽  
Vol 69 (2) ◽  
pp. 1160-1171 ◽  
Author(s):  
David T. Pride ◽  
Richard J. Meinersmann ◽  
Martin J. Blaser
Keyword(s):  
Helicobacter Pylori ◽  
Allelic Variation ◽  
Outer Membrane Proteins ◽  
Functional Constraints ◽  
Paralogous Family ◽  
Central Regions ◽  
H Pylori ◽  
Synonymous And Nonsynonymous Substitutions ◽  
Host Blood ◽  
Determining Factor

ABSTRACT Helicobacter pylori strains show both geographic and disease-associated allelic variation. We investigated the diversity present in two genes, babA and babB, which are members of a paralogous family of outer membrane proteins. Eleven family members within a single H. pylori strain, predicted to encode proteins with substantial N- and C-terminal similarity to each other, were classified as babA paralogues. In their central regions, most are less than 54% related to one another. Examining the babA and babB central regions in 42 H. pylori strains from different geographic locales, we identified five different allele groups of babA (AD1 to AD5) and three different allele groups of babB (BD1 to BD3). Phylogenetic analysis revealed that the allelic groupings ofbabA and babB are independent of one another and that, for both, geographic variation is present. Analysis of synonymous and nonsynonymous substitutions in these regions showed thatbabA is more diverse, implying an earlier origin than that of the same region of babB, but that the babAdiversity region may have more functional constraints. Although recombination has been central to the evolution of both genes, withbabA and babB showing low mean compatibility scores and homoplasy ratios of 0.71 and 0.67, respectively, recombination is not sufficient to obscure evidence of clonal descent. Despite the involvement of babA in binding to the host blood group antigen Lewis B, neither the presence of differentbabA allele groups nor that of different babBallele groups is a determining factor in Lewis B binding of H. pylori strains.

scholarly journals Comparative Genomics of Helicobacter pylori: Analysis of the Outer Membrane Protein Families

2000 ◽  
Vol 68 (7) ◽  
pp. 4155-4168 ◽  
Author(s):  
Richard A. Alm ◽  
James Bina ◽  
Beth M. Andrews ◽  
Peter Doig ◽  
Robert E. W. Hancock ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Gene Families ◽  
Ancestral Gene ◽  
Related Function ◽  
Paralogous Family ◽  
H Pylori ◽  
Complete Genomic

ABSTRACT The two complete genomic sequences of Helicobacter pylori J99 and 26695 were used to compare the paralogous families (related genes within one genome, likely to have related function) of genes predicted to encode outer membrane proteins which were present in each strain. We identified five paralogous gene families ranging in size from 3 to 33 members; two of these families contained members specific for either H. pylori J99 or H. pylori26695. Most orthologous protein pairs (equivalent genes between two genomes, same function) shared considerable identity between the two strains. The unusual set of outer membrane proteins and the specialized outer membrane may be a reflection of the adaptation of H. pylori to the unique gastric environment where it is found. One subfamily of proteins, which contains both channel-forming and adhesin molecules, is extremely highly related at the sequence level and has likely arisen due to ancestral gene duplication. In addition, the largest paralogous family contained two essentially identical pairs of genes in both strains. The presence and genomic organization of these two pairs of duplicated genes were analyzed in a panel of independentH. pylori isolates. While one pair was present in every strain examined, one allele of the other pair appeared partially deleted in several isolates.

scholarly journals Allelic Diversity among Helicobacter pylori Outer Membrane Protein Genes homB and homA Generated by Recombination

2010 ◽  
Vol 192 (15) ◽  
pp. 3961-3968 ◽  
Author(s):  
Mónica Oleastro ◽  
Rita Cordeiro ◽  
Armelle Ménard ◽  
João Paulo Gomes
Keyword(s):  
Helicobacter Pylori ◽  
Homologous Recombination ◽  
Outer Membrane ◽  
Molecular Analysis ◽  
Allelic Variation ◽  
Outer Membrane Proteins ◽  
Allelic Diversity ◽  
Molecular Profile ◽  
Allelic Variants ◽  
H Pylori

ABSTRACT Recombination is one of the main mechanisms contributing to Helicobacter pylori genomic variability. homB and homA are paralogous genes coding for H. pylori outer membrane proteins (OMPs). Both genes display allelic variation yielded by polymorphisms of the genes' middle regions, with six different alleles. This study used bioinformatic and statistical analyses to evaluate whether the allelic diversity of homB and homA is generated by recombination. A detailed molecular analysis of the most prevalent homB allelic variant was also performed to establish its molecular profile. The two most prevalent homB and homA allelic variants resulted from interallelic homologous recombination between the rarest allelic variants of each gene, with a crossover point localized in the middle of the genes, containing the allelic region. Molecular analysis of the most prevalent homB allele revealed a geographic partition among Western and East Asian strains, more noticeable for the 5′ and 3′ homB regions than for the middle allelic regions. In conclusion, the diversity of the 5′ and 3′ homB regions reflect the strains' geographical origin, and variants likely occur via the accumulation of single nucleotide polymorphisms. On the other hand, homologous recombination seems to play an important role in the diversification of the highly polymorphic homB and homA allele-defining regions, where the most prevalent alleles worldwide result from genomic exchange between the rarest variants of each gene, suggesting that the resulting combinations confer biological advantages to H. pylori. This phenomenon illustrates an evolutionary scenario in which recombination appears to be associated with ecological success.

scholarly journals Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 331
Author(s):  
Montserrat Palau ◽  
Núria Piqué ◽  
M. José Ramírez-Lázaro ◽  
Sergio Lario ◽  
Xavier Calvet ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Virulence Factors ◽  
Outer Membrane Proteins ◽  
Whole Genome ◽  
Flagellar Biosynthesis ◽  
H Pylori ◽  
Restriction Modification

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

Enhanced fitness of a Helicobacter pylori babA mutant in a murine model

2021 ◽  
Author(s):  
M. Lorena Harvey ◽  
Aung Soe Lin ◽  
Lili Sun ◽  
Tatsuki Koyama ◽  
Jennifer H. B. Shuman ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane Proteins ◽  
Population Diversity ◽  
Fitness Advantage ◽  
Neutral Locus ◽  
Mutant Strains ◽  
Bacterial Fitness ◽  
H Pylori

Helicobacter pylori genomes encode >60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify hop mutant strains that exhibit altered fitness in vivo compared to fitness in vitro , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of hop mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time in vivo compared to changes detected in the populations during library passage in vitro . The control library proliferated as a relatively stable community in vitro, but there was a reduction in the population diversity of this library in vivo and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a non-selective bottleneck in vivo . We did not identify any OMP mutants exhibiting fitness defects exclusively in vivo without corresponding fitness defects in vitro . Conversely, a babA mutant exhibited a strong fitness advantage in vivo but not in vitro . These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.

RAPID CHARACTERIZATION AND SEPARATION OF ISOGENIC MUTANTS OF H. PYLORI BY DIELECTROPHORESIS

2009 ◽  
Vol 21 (06) ◽  
pp. 433-436
Author(s):  
Chi-Chang Lin ◽  
Sheng-Kai Li ◽  
Bor-Shyang Sheu ◽  
Hsien-Chang Chang
Keyword(s):  
Helicobacter Pylori ◽  
Individual Cell ◽  
Outer Membrane Proteins ◽  
Cell Types ◽  
Wild Type ◽  
Nondestructive Analysis ◽  
Isogenic Mutant ◽  
Rapid Characterization ◽  
H Pylori ◽  
Isogenic Mutants

A simple, fast, real-time, and nondestructive analysis of protein expression in biological samples, such as membranes, based on dielectrophoresis is described. On the basis of the distinct differences in the dielectrophoretic properties of individual cell types, the wild-type BabA-positive Helicobacter pylori isolates and its BabA-negative isogenic mutant can be identified and separated. The herein-presented approach of using microelectrodes should be an easy-to-use, cheap, and rapid alternative to separate and distinguish the presence or absence of important outer-membrane proteins.

scholarly journals Comparison of CXC Chemokines ENA-78 and Interleukin-8 Expression in Helicobacter pylori-Associated Gastritis

2001 ◽  
Vol 69 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Gabriele Rieder ◽  
Wolfgang Einsiedl ◽  
Rudolf A. Hatz ◽  
Manfred Stolte ◽  
Georg A. Enders ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Protein Expression ◽  
Outer Membrane Proteins ◽  
Water Soluble ◽  
Interleukin 8 ◽  
Gastric Epithelium ◽  
Mrna Levels ◽  
Rt Pcr ◽  
H Pylori

ABSTRACT Colonization of the gastric mucosa with Helicobacter pylori is associated with a dense infiltration of granulocytes into the lamina propria in the active phase of gastritis. In this study, we investigated the involvement of epithelial cell-derived neutrophil-activating protein 78 (ENA-78) in development of H. pylori-associated gastritis. Antral biopsies from 27 patients with H. pylori-associated gastritis and 25 from H. pylori-negative individuals were first analyzed for ENA-78 and interleukin-8 (IL-8) mRNA by semiquantitative reverse transcription (RT)-PCR. In H. pylori-positive patients, significantly elevated levels were found for both chemokines (P < 0.05). Only IL-8 mRNA levels differed significantly (P< 0.05) in H. pylori-infected individuals who had serum antibodies for cytotoxin-associated protein CagA versus H. pylori-infected CagA-negative persons. Quantification of ENA-78 transcript levels by competitive RT-PCR yielded a significant 45-fold upregulation for ENA-78 transcripts in biopsies of H. pylori-positive versus H. pylori-negative patients (P < 0.05). In contrast to earlier findings with IL-8, the degree of ENA-78 mRNA upregulation was independent of the grade of activity of gastritis. Immunofluorescence studies on tissues of antral biopsies localized ENA-78 protein expression mainly to the gastric epithelium of H. pylori-positive patients, while control tissues were negative. Upregulation of ENA-78 and IL-8 mRNA and protein expression was also observed in an in vitro system using a gastric adenocarcinoma cell line. Only viable H. pyloriyielded a strong ENA-78 and IL-8 induction, while H. pyloriouter membrane proteins or water-soluble proteins had no significant effect. These data provide evidence for the importance of both IL-8 and ENA-78 in the development and perpetuation of H. pylori-associated gastritis.

scholarly journals The Role of a Dipeptide Transporter in the Virulence of Human Pathogen, Helicobacter pylori

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaohong Xu ◽  
Junwei Chen ◽  
Xiaoxing Huang ◽  
Shunhang Feng ◽  
Xiaoyan Zhang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factors ◽  
Outer Membrane Proteins ◽  
Wild Type ◽  
Ags Cells ◽  
Dipeptide Transporter ◽  
Adhesion Level ◽  
H Pylori ◽  
Substrate Binding Protein

Helicobacter pylori harbors a dipeptide (Dpp) transporter consisting of a substrate-binding protein (DppA), two permeases (DppB and C), and two ATPases (DppD and F). The Dpp transporter is responsible for the transportation of dipeptides and short peptides. We found that its expression is important for the growth of H. pylori. To understand the role of the Dpp transporter in the pathogenesis of H. pylori, the expression of virulence factors and H. pylori-induced IL-8 production were investigated in H. pylori wild-type and isogenic H. pylori Dpp transporter mutants. We found that expression of CagA was downregulated, while expression of type 4 secretion system (T4SS) components was upregulated in Dpp transporter mutants. The DppA mutant strain expressed higher levels of outer membrane proteins (OMPs), including BabA, HopZ, OipA, and SabA, and showed a higher adhesion level to gastric epithelial AGS cells compared with the H. pylori 26695 wild-type strain. After infection of AGS cells, H. pylori ΔdppA induced a higher level of NF-κB activation and IL-8 production compared with wild-type. These results suggested that in addition to supporting the growth of H. pylori, the Dpp transporter causes bacteria to alter the expression of virulence factors and reduces H. pylori-induced NF-κB activation and IL-8 production in gastric epithelial cells.

scholarly journals Helicobacter pylori BabA–SabA Key Roles in the Adherence Phase: The Synergic Mechanism for Successful Colonization and Disease Development

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 485
Author(s):  
Dalla Doohan ◽  
Yudith Annisa Ayu Rezkitha ◽  
Langgeng Agung Waskito ◽  
Yoshio Yamaoka ◽  
Muhammad Miftahussurur
Keyword(s):  
Helicobacter Pylori ◽  
Defense Mechanisms ◽  
Outer Membrane Proteins ◽  
Lewis Antigens ◽  
Mucosal Tissue ◽  
Self Defense ◽  
Sialic Acid Binding ◽  
Adherence Mechanism ◽  
Colonization Process ◽  
H Pylori

Helicobacter pylori is a pathogenic microorganism that successfully inhabits the human stomach, colonizing it by producing several virulence factors responsible for preventing host self-defense mechanisms. The adherence mechanism to gastric mucosal tissue is one of the most important processes for effective colonization in the stomach. The blood group antigen-binding adhesion (BabA) and sialic acid-binding adherence (SabA) are two H. pylori outer membrane proteins able to interact with antigens in the gastroduodenal tract. H. pylori possesses several mechanisms to control the regulation of both BabA and SabA in either the transcriptional or translational level. BabA is believed to be the most important protein in the early infection phase due to its ability to interact with various Lewis antigens, whereas SabA interaction with sialylated Lewis antigens may prove important for the adherence process in the inflamed gastric mucosal tissue in the ongoing-infection phase. The adherence mechanisms of BabA and SabA allow H. pylori to anchor in the gastric mucosa and begin the colonization process.

scholarly journals Proteomic Analysis of the Sarcosine-Insoluble Outer Membrane Fraction of Helicobacter pylori Strain 26695

2004 ◽  
Vol 186 (4) ◽  
pp. 949-955 ◽  
Author(s):  
Seung-Chul Baik ◽  
Kyung-Mi Kim ◽  
Su-Min Song ◽  
Do-Su Kim ◽  
Jin-Su Jun ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Proteomic Analysis ◽  
Membrane Fraction ◽  
Outer Membrane Proteins ◽  
Immunoblot Analysis ◽  
Outer Membrane Fraction ◽  
Flight Mass Spectrometry ◽  
Molecular Masses ◽  
H Pylori

ABSTRACT Helicobacter pylori causes gastroduodenal disease, which is mediated in part by its outer membrane proteins (OMPs). To identify OMPs of H. pylori strain 26695, we performed a proteomic analysis. A sarcosine-insoluble outer membrane fraction was resolved by two-dimensional electrophoresis with immobilized pH gradient strips. Most of the protein spots, with molecular masses of 10 to 100 kDa, were visible on the gel in the alkaline pI regions (6.0 to 10.0). The proteome of the OMPs was analyzed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Of the 80 protein spots processed, 62 spots were identified; they represented 35 genes, including 16 kinds of OMP. Moreover, we identified 9 immunoreactive proteins by immunoblot analysis. This study contributes to the characterization of the H. pylori strain 26695 proteome and may help to further elucidate the biological function of H. pylori OMPs and the pathogenesis of H. pylori infection.

scholarly journals Genomic differentiation within East Asian Helicobacter pylori

2021 ◽  
Author(s):  
Yuanhai You ◽  
Kaisa Thorell ◽  
Lihua He ◽  
Koji Yahara ◽  
Yoshio Yamaoka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Amino Acid ◽  
Cancer Incidence ◽  
Outer Membrane Proteins ◽  
East Asian ◽  
Fixation Index ◽  
3D Protein Structure ◽  
Local Conditions ◽  
H Pylori

The East Asian region, including China, Japan and Korea, accounts for half of gastric cancer deaths. However, different areas have contrasting gastric cancer incidence and the population structure of Helicobacter pylori in this ethnically diverse region is yet unknown. We aimed to investigate genomic differences in H. pylori between these areas to identify sequence polymorphisms associated with increased cancer risk. We analysed 381 H. pylori genomes collected from different areas of the three countries using phylogenetic and population genetic tools to characterize population differentiation. The functional consequences of Single Nucleotide Polymorphisms (SNPs) with a highest fixation index (Fst) between subpopulations were examined by mapping amino-acid changes on 3D protein structure, solved or modelled. 329/381 genomes belonged to the previously identified hspEAsia population indicating that import of bacteria from other regions of the world has been uncommon. Seven sub-regional clusters were found within hspEAsia, related to sub-populations with various ethnicities, geographies and gastric cancer risks. Sub-population-specific amino-acid changes were found in multi-drug exporters (hefC), transporters (frpB-4), outer membrane proteins (hopI), and several genes involved in host interaction, such as catalase, involved in H2O2 entrance, and a flagellin site mimicking host glycosylation. Several of the top hits including frpB-4, hefC, alpB/hopB, and hofC. were also differentiated within the Americas, indicating that a handful of genes may be key to local geographic adaptation. H. pylori within East Asia are not homogeneous but have become differentiated geographically at multiple loci that have facilitated adaptation to local conditions and hosts. This has important implications for further evaluation of these changes in relation to the varying gastric cancer incidence between geographical areas in this region.

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