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BETA
Vallström, Anna
Alternative names
Publications (10 of 11) Show all publications
diva2:1258792
Open this publication in new window or tab >>Helicobacter pylori Outer Membrane Vesicles Protect the Pathogen From Reactive Oxygen Species of the Respiratory Burst
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2018 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, article id 1837Article in journal (Refereed) Published
Abstract [en]

Outer membrane vesicles (OMVs) play an important role in the persistence of Helicobacter pylori infection. Helicobacter OMVs carry a plethora of virulence factors, including catalase (KatA), an antioxidant enzyme that counteracts the host respiratory burst. We found KatA to be enriched and surface-associated in OMVs compared to bacterial cells. This conferred OMV-dependent KatA activity resulting in neutralization of H2O2 and NaClO, and rescue of surrounding bacteria from oxidative damage. The antioxidant activity of OMVs was abolished by deletion of KatA. In conclusion, enrichment of antioxidative KatA in OMVs is highly important for efficient immune evasion.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
H. pylori, KatA, outer membrane vesicles, oxidative burst, reactive oxygen species
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-152205 (URN)10.3389/fmicb.2018.01837 (DOI)000443976200001 ()30245670 (PubMedID)
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2018-10-25Bibliographically approved
Åberg, A., Gideonsson, P., Vallström, A., Olofsson, A., Öhman, C., Rakhimova, L., . . . Arnqvist, A. (2014). A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism. PLoS Pathogens, 10(7), Article ID e1004234.
Open this publication in new window or tab >>A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism
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2014 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, no 7, article id e1004234Article in journal (Refereed) Published
Abstract [en]

During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, the SSRs generate heterogeneous populations that facilitate adaptation. Here, we present a model that explains, in molecular terms, how an intergenically located T-tract, via slipped strand mispairing, operates with a rheostat-like function, to fine-tune activity of the promoter that drives expression of the sialic acid binding adhesin, SabA. Using T-tract variants, in an isogenic strain background, we show that the length of the T-tract generates multiphasic output from the sabA promoter. Consequently, this alters the H. pylori binding to sialyl-Lewis x receptors on gastric mucosa. Fragment length analysis of post-infection isolated clones shows that the T-tract length is a highly variable feature in H. pylori. This mirrors the host-pathogen interplay, where the bacterium generates a set of clones from which the best-fit phenotypes are selected in the host. In silico and functional in vitro analyzes revealed that the length of the T-tract affects the local DNA structure and thereby binding of the RNA polymerase, through shifting of the axial alignment between the core promoter and UP-like elements. We identified additional genes in H. pylori, with T- or A-tracts positioned similar to that of sabA, and show that variations in the tract length likewise acted as rheostats to modulate cognate promoter output. Thus, we propose that this generally applicable mechanism, mediated by promoter-proximal SSRs, provides an alternative mechanism for transcriptional regulation in bacteria, such as H. pylori, which possesses a limited repertoire of classical trans-acting regulatory factors.

National Category
Physiology Physical Chemistry
Identifiers
urn:nbn:se:umu:diva-91641 (URN)10.1371/journal.ppat.1004234 (DOI)000340551000026 ()24991812 (PubMedID)
Available from: 2014-08-13 Created: 2014-08-13 Last updated: 2018-06-07Bibliographically approved
Ohno, T., Vallström, A., Rugge, M., Ota, H., Graham, D. Y., Arnqvist, A. & Yamaoka, Y. (2011). Effects of blood group antigen-binding adhesin expression during Helicobacter pylori infection of Mongolian gerbils. Journal of Infectious Diseases, 203(5), 726-735
Open this publication in new window or tab >>Effects of blood group antigen-binding adhesin expression during Helicobacter pylori infection of Mongolian gerbils
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2011 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 203, no 5, p. 726-735Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori outer membrane proteins, such as the blood group antigen-binding adhesin (BabA), are associated with severe pathological outcomes. However, the in vivo role of BabA during long-term infection is not clear. In this study, Mongolian gerbils were infected with H. pylori and necropsied continuously during 18 months. Bacterial clones were recovered and analyzed for BabA expression, Leb-binding activity, and adhesion to gastric mucosa. BabA expression was completely absent by 6 months post-infection. Loss of BabA expression was attributable to nucleotide changes within the babA gene that resulted in a truncated BabA. In response to the infection, changes in the epithelial glycosylation pattern were observed that were similar to responses observed in humans and monkeys. Furthermore, infections with BabA-expressing and BabA-nonexpressing H. pylori showed no differences in colonization, but infection with the BabA-expressing strain exhibited histological changes and increased inflammatory cell infiltration. This suggests that BabA expression contributes to severe mucosal injury.

Keywords
outer-membrane proteins; baba; inflammation; activation; attachment; gastritis; gene; oipa
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-41100 (URN)10.1093/infdis/jiq090 (DOI)21227917 (PubMedID)
Available from: 2011-03-17 Created: 2011-03-17 Last updated: 2018-06-08Bibliographically approved
Olofsson, A., Vallström, A., Petzold, K., Tegtmeyer, N., Schleucher, J., Carlsson, S., . . . Arnqvist, A. (2010). Biochemical and functional characterization of Helicobacter pylori vesicles. Molecular Microbiology, 77(6), 1539-1555
Open this publication in new window or tab >>Biochemical and functional characterization of Helicobacter pylori vesicles
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2010 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 77, no 6, p. 1539-1555Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. Adhesion of bacteria to the stomach mucosa is an important contributor to the vigor of infection and resulting virulence. H. pylori adheres primarily via binding of BabA adhesins to ABO/Lewis b (Leb) blood group antigens and the binding of SabA adhesins to sialyl-Lewis x/a (sLex/a) antigens. Similar to most Gram-negative bacteria, H. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often include virulence-associated factors. Here we biochemically characterized highly purified H. pylori vesicles. Major protein and phospholipid components associated with the vesicles were identified with mass spectroscopy and NMR. A subset of virulence factors present was confirmed by immunoblots. Additional functional and biochemical analysis focused on the vesicle BabA and SabA adhesins and their respective interactions to human gastric epithelium. Vesicles exhibit heterogeneity in their protein composition, which were specifically studied in respect to the BabA adhesin. We also demonstrate that the oncoprotein, CagA, is associated with the surface of H. pylori vesicles. Thus, we have explored mechanisms for intimate H. pylori vesicle-host interactions and found that the vesicles carry effector-promoting properties that are important to disease development.

Place, publisher, year, edition, pages
Wiley, 2010
Identifiers
urn:nbn:se:umu:diva-35586 (URN)10.1111/j.1365-2958.2010.07307.x (DOI)000281831400018 ()20659286 (PubMedID)
Available from: 2010-08-24 Created: 2010-08-24 Last updated: 2018-06-08Bibliographically approved
Vallström, A. (2009). Helicobacter pylori: molecular mechanisms for variable adherence properties. (Doctoral dissertation). Umeå: Umeå university
Open this publication in new window or tab >>Helicobacter pylori: molecular mechanisms for variable adherence properties
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

More than half of all people worldwide are infected with H. pylori. The infection always cause a gastric inflammation that may develop into peptic ulcer disease or gastric cancer. Attachment proteins, adhesins, mediate specific adherence of H. pylori to receptor structures on the human gastric mucosa. The best-characterized H. pylori adhesin-receptor interactions are the BabA adhesin and the binding to the fucosylated blood group antigens ABO/Lewis b (Leb) and the SabA adhesin and its binding to the inflammation associated sialyl-Lewis x antigen. During H. pylori infection the availability of receptor structures on the human gastric mucosa changes as a consequence of the host inflammatory and immune responses. Consequently the bacterial population need to adjust its adherence properties to stay colonized. This thesis describes mechanisms that generate H. pylori populations with variable adherence properties and mechanisms for adjustment of adhesin expression levels.In H. pylori strains devoid of Leb-binding, we found bacterial cells with Leb-binding. Isolation of such H. pylori clones demonstrated that the change in receptor binding phenotype was obtained via the mechanisms of homologous recombination and slipped strand mispairing (SSM). Disease presentation in relation to BabA expression was studied in H. pylori infected Mongolian gerbils. We showed that BabA was not essential for colonization but caused severe injury to the gastric mucosa and was turned off during long-term infection by nucleotide changes within the babA gene. Gerbils infected with BabA-weak-expressing strains maintained BabA expressing clones for a longer period than gerbils that were infected with BabA-high-expressing strains. Studies of the gerbil gastric mucosal glycosylation showed that gerbils respond in a similar way as humans and Rhesus monkeys which support gerbils to be a model suitable for studying H. pylori infection and disease outcome in relation to adherence.We studied the SSM mechanism of SabA phase variation and the cognate shift in sLex-binding phenotype and we show sLex-binding activity to be growth phase dependent. H. pylori vesicles were characterized for the major phosholipid and protein components. Virulence factors e.g., VacA, and CagA were identified and both the BabA and the SabA adhesins was shown to be located on the vesicle surface and to mediate specific binding to their cognate receptors present on the human gastric mucosa. H. pylori generate bacterial cells with different receptor binding phenotypes via the mechanisms of homologous recombination, SSM and nucleotide changes. These mechanisms will probably contribute to bacterial fitness by the generation of quasi species populations where some of the clones will be better adapted to the environmental chances during persistent infection.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2009. p. 57
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1280
Keywords
H. pylori, adherence, BabA, SabA, Leb, sLex, phase variation, recombination, vesicles
Identifiers
urn:nbn:se:umu:diva-25931 (URN)978-91-7264-820-3 (ISBN)
Distributor:
Oral mikrobiologi, 901 87, Umeå
Public defence
2009-10-09, KBC3A9, plan 3, KBC-huset, Umeå Universitet, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2009-09-21 Created: 2009-09-13 Last updated: 2018-06-08Bibliographically approved
Olofsson, A., Bäckström, A., Petzold, K., Gröbner, G., Wai, S., Carlsson, S., . . . Arnqvist, A. (Eds.). (2007). Helicobacter pylori outer membrane vesicles and properties for intimate host interactions. BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
Open this publication in new window or tab >>Helicobacter pylori outer membrane vesicles and properties for intimate host interactions
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2007 (English)Conference proceedings (editor) (Refereed)
Place, publisher, year, edition, pages
BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND, 2007
Identifiers
urn:nbn:se:umu:diva-11601 (URN)
Note
Meeting Abstract ZOONOSES AND PUBLIC HEALTH Volume: 54 Pages: 93-94 Supplement: Suppl. 1 Published: 2007Available from: 2009-01-22 Created: 2009-01-22 Last updated: 2018-06-09Bibliographically approved
diva2:146319
Open this publication in new window or tab >>Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin
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2004 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 305, no 5683, p. 519-522Article in journal (Refereed) Published
Abstract [en]

Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.

Place, publisher, year, edition, pages
American Association for the Advancement of Science, 2004
Keywords
ABO Blood-Group System/*metabolism, Adaptation; Biological, Adhesins; Bacterial/chemistry/*genetics/immunology/*metabolism, Alleles, Bacterial Adhesion, Base Sequence, Binding Sites, Evolution; Molecular, Fucose/metabolism, Gastric Mucosa/microbiology, Helicobacter Infections/microbiology, Helicobacter pylori/genetics/immunology/*physiology, Humans, Indians; South American, Lewis Blood-Group System/metabolism, Molecular Sequence Data, Mutation, Peru, Phenotype, Phylogeny, Protein Binding, Selection (Genetics), Transformation; Bacterial
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-6649 (URN)10.1126/science.1098801 (DOI)000222828900040 ()15273394 (PubMedID)
Available from: 2008-01-08 Created: 2008-01-08 Last updated: 2019-01-22Bibliographically approved
Bäckström, A., Lundberg, C., Kersulyte, D., Berg, D. E., Borén, T. & Arnqvist, A. (2004). Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding. Proceedings of the National Academy of Sciences of the United States of America, 101(48), 16923-16928
Open this publication in new window or tab >>Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding
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2004 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, no 48, p. 16923-16928Article in journal (Refereed) Published
Keywords
Adhesins; Bacterial/*genetics/immunology, Base Sequence, Blotting; Northern, Blotting; Southern, Helicobacter pylori/*genetics, Lewis Blood-Group System/*immunology, Microscopy; Fluorescence, Molecular Sequence Data, RNA; Messenger/genetics, Recombinant Fusion Proteins/immunology
Identifiers
urn:nbn:se:umu:diva-6648 (URN)10.1073/pnas.0404817101 (DOI)15557006 (PubMedID)
Available from: 2007-12-16 Created: 2007-12-16 Last updated: 2018-06-09Bibliographically approved
Olofsson, A., Vallström, A., Petzold, K., Schleucher, J., Carlsson, S., Haas, R., . . . Arnqvist, A. Characterization of Helicobacter pylori vesicles and their cognate properties for intimate host interactions.
Open this publication in new window or tab >>Characterization of Helicobacter pylori vesicles and their cognate properties for intimate host interactions
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(English)Manuscript (preprint) (Other academic)
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-25737 (URN)
Available from: 2009-09-01 Created: 2009-09-01 Last updated: 2018-06-08Bibliographically approved
Ohno, T., Vallström, A., Wu, M., Rugge, M., Ota, H., Graham, D. Y., . . . Yamaoka, Y.Effects of BabA expression during H. pylori infection of Mongolian gerbils.
Open this publication in new window or tab >>Effects of BabA expression during H. pylori infection of Mongolian gerbils
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: Helicobacter pylori outer membrane proteins, such as the BabA adhesin are associated with severe pathological outcome.  However, the in vivo role of the BabA adhesin during long-term infection is not clear.  Design and Setting: Mongolian gerbils were inoculated with the H. pylori TN2GF4 and were necropsied at 1, 3, 6, and 18 months.  Main outcome measures: Bacterial clones recovered from the infected gerbils were evaluated by immunoblot for BabA expression, radioimmunoassay for Leb-binding, and bacterial binding to gastric tissue.  H1 antigen expression and the increase in sialylation levels were monitored by immunohistochemistry.  Results: BabA expression increased, then progressively decreased, and was completely absent by 6 months post-infection.  Loss of BabA expression was caused by nucleotide changes/deletions within the babA gene that resulted in a truncated BabA.  Infection with a BabA-expressing H. pylori caused severe mucosal injury, whereas infection with a BabA non-expressing strain caused only mild inflammation.  In response to the infection, changes in the epithelial glycosylation pattern were observed, similar to responses observed in humans and monkeys.  Conclusion: Down-regulation of BabA is probably a result of adaptation to the host response during long-term H. pylori infection.  BabA expression is most likely not essential for colonisation, but for the obtained gerbil host response, which confirms the role of BabA adhesin as a virulence factor and its impact in the induction of a severe inflammatory response.  The changes in glycosylation of gastric mucosa demonstrate the relevance of the Mongolian gerbil as a model for H. pylori infection and host responses.

Identifiers
urn:nbn:se:umu:diva-25930 (URN)
Available from: 2009-09-13 Created: 2009-09-13 Last updated: 2018-06-08Bibliographically approved
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