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Nordén, Jenny
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Publikasjoner (5 av 5) Visa alla publikasjoner
Moonens, K., Gideonsson, P., Subedi, S., Bugaytsova, J., Romao, E., Mendez, M., . . . Remaut, H. (2016). Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. Cell Host and Microbe, 19(1), 55-66
Åpne denne publikasjonen i ny fane eller vindu >>Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori
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2016 (engelsk)Inngår i: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 19, nr 1, s. 55-66Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le b blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

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Identifikatorer
urn:nbn:se:umu:diva-117839 (URN)10.1016/j.chom.2015.12.004 (DOI)000369839900010 ()26764597 (PubMedID)2-s2.0-84959550066 (Scopus ID)
Tilgjengelig fra: 2016-04-04 Laget: 2016-03-04 Sist oppdatert: 2024-07-02bibliografisk kontrollert
Norlin, J., Schmitt-Egenolf, M., Steen Carlsson, K. & Persson, U. (2014). Registerstudier mäter effektivitet av läkemedel i klinisk praxis: Exemplet PsoReg – omfördelning av systemisk terapi kan ge ökad effektivitet. Läkartidningen, 111(24), 1061-3
Åpne denne publikasjonen i ny fane eller vindu >>Registerstudier mäter effektivitet av läkemedel i klinisk praxis: Exemplet PsoReg – omfördelning av systemisk terapi kan ge ökad effektivitet
2014 (svensk)Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 24, s. 1061-3Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [sv]

Läkemedel och medicinska teknologier fungerar inte likadant i klinisk praxis som i randomiserade kliniska prövningar.

Studier baserade på kvalitetsregister kan bidra med kompletterande information om läkemedels effektivitet i klinisk vardag. 

Analyser av data från PsoReg, det nationella kvalitetsregistret för systemisk behandling av psoria­sis, indikerar att det förekommer såväl över- som underbehandling med biologiska läkemedel av patienter med psoriasis.

Genom att optimera fördelningen av biologisk systemisk behandling mellan patienter kan den totala hälsonivån öka utan att sjukvårdsbudgeten ökar.

Abstract [en]

Pharmaceuticals and medical technologies may have different outcomes in randomized controlled trials and observational studies. Register-based research can provide complementary information about the effectiveness of new medical technologies in clinical practice. Studies based on PsoReg, the Swedish register for systemic treatment of psoriasis, indicate that there is both an over- and under-treatment with biologics in patients with psoriasis in clinical practice. By optimizing the allocation of biologic systemic treatments for psoriasis the overall health level would increase without increas­ing the budget.

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Identifikatorer
urn:nbn:se:umu:diva-95478 (URN)25129915 (PubMedID)2-s2.0-84902095998 (Scopus ID)
Tilgjengelig fra: 2014-10-30 Laget: 2014-10-30 Sist oppdatert: 2024-07-02bibliografisk kontrollert
Nordén, J. (2011). Multifaceted adhesion properties of Helicobacter pylori in promotion of gastric disease. (Licentiate dissertation). Umeå: Umeå universitet
Åpne denne publikasjonen i ny fane eller vindu >>Multifaceted adhesion properties of Helicobacter pylori in promotion of gastric disease
2011 (engelsk)Licentiatavhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Helicobacter pylori is a Gram-negative spiral-shaped bacteria that resides in the gastric mucosa and adheres to the epithelial lining of the human stomach. H. pylori adhesion mediates inflammation of the epithelium, which can lead to more severe diseases such as chronic active gastritis and gastric carcinoma. In order to adhere tightly to the mucosal lining, H. pylori expresses adhesion proteins called adhesins. The best-charachterized adhesins are blood group antigen binding adhesin, BabA, and sialic acid binding adhesin, SabA. During chronic infection there is an adhesion/inflammation-associated balance between BabA- and SabA-mediated binding modes. BabA is the major mediator of binding when the stomach is in good health and the corresponding binding receptors are ABO blood group antigens such as the difucosylated Lewis b antigen that is expressed on MUC5AC mucins by the surface epithelium. However, in chronic inflammation of the gastric mucosa there are dynamic shifts in the glycosylation patterns; in inflamed gastric tissue, SabA is an important mediator of bacterial binding and adherence. The corresponding binding receptors for the SabA adhesin are complex sialylated antigens such as sLewis x (sLex) and sLewis a (sLea). In this thesis, I describe our findings that SabA also promotes H. pylori binding to red blood cells in the gastric mucosal small blood vessels. The minimal binding epitope on the erythrocyte surfaces is the sialylated NeuAcα2-3Gal-disaccharide and this bacterial adherence promotes hemagglutination, i.e. the rapid aggregation of the erythrocytes.

Another important finding is that the binding properties of SabA are of polymorphic nature. In particular, clinical isolates demonstrate variant types of relative binding affinity for the series of sialyl-di Lewis x (sdiLex), sialyl-Lewis a (sLea) and sialyl-lactosamine (sLn). The relative binding to sialylated glycans is strain dependent and H. pylori strains J99 and SMI9 display different SabA-mediated binding modes for sialylated glycans. By introduction of the sabA gene from strain J99 into strain SMI9, the detailed binding mode of SMI9sabAJ99 was altered and preferably displayed the original binding mode of strain J99. Thus, the polymorphism of SabA-mediated binding is an inherent property of the adhesion protein itself, i.e. the polypeptide itself and is not encoded or influenced by the strain genome background. The individualized binding properties or polymorphism in binding modes provides SabA with the opportunity to adapt to individual hosts and to the inflammatory changes in glycosylation. SabA expression makes use of slipped-strand mispairing for H. pylori to swiftly attach and detach from the epithelium. Furthermore, the ability to fluently attach and detach from the epithelial surfaces is an important feature of H. pylori and its ability to evade the mucosal inflammatory responses, as well as from the rapid turnover and shedding of gastric mucosa. Here, I describe a novel blood group antigen binding outer membrane protein, FecA3. This is an adhesin candidate, which independently of BabA, binds the series of fucosylated blood group antigens. The similar binding modes of BabA and FecA3 for ABO blood group antigens is not fully understood but the expression of FecA3 is regulated by the nickel-responsive regulator NikR, which acts as a sensor regulated by the availability of free nickel ions. Ni2+increases when pH is lowered, thus regulation of FecA3 is suggested to be governed by local pH. Taken together, the high-affinity binding by BabA, and continuous biopanning for the fittest, in particular for the low-affinity binding of FecA3, might be contrasting but complementary properties and features of the different adhesins that are of importance during different stages of mucosal inflammation and disease development.

sted, utgiver, år, opplag, sider
Umeå: Umeå universitet, 2011. s. 34
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-56320 (URN)978-91-7459-336-5 (ISBN)
Tilgjengelig fra: 2012-06-14 Laget: 2012-06-14 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Aspholm, M., Olfat, F. O., Nordén, J., Sondén, B., Lundberg, C., Sjöström, R., . . . Borén, T. (2006). SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.. PLoS Pathog, 2(10), e110
Åpne denne publikasjonen i ny fane eller vindu >>SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
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2006 (engelsk)Inngår i: PLoS Pathog, ISSN 1553-7374, Vol. 2, nr 10, s. e110-Artikkel i tidsskrift (Fagfellevurdert) Published
Emneord
Adhesins; Bacterial/genetics/*metabolism, Adsorption, Animals, Antigens; Bacterial/metabolism, Bacterial Adhesion, Binding Sites, Binding; Competitive, Capillaries, Erythrocytes/metabolism/microbiology, Gangliosides/metabolism, Gastric Mucosa/blood supply/microbiology, Gene Deletion, Helicobacter Infections/immunology/microbiology, Helicobacter pylori/metabolism/*physiology, Hemagglutination, Hemagglutinins/*metabolism, Humans, Macaca mulatta, N-Acetylneuraminic Acid/*metabolism, Oligosaccharides/metabolism, Polysaccharides/*metabolism, Venules
Identifikatorer
urn:nbn:se:umu:diva-6639 (URN)17121461 (PubMedID)2-s2.0-33750489397 (Scopus ID)
Tilgjengelig fra: 2007-12-16 Laget: 2007-12-16 Sist oppdatert: 2024-07-02bibliografisk kontrollert
Nordén, J., Westermark, M., Bugaytsova, J., Mendez, A., Henriksson, S. & Borén, T.Characterization of BabA independent binding activity for ABO blood group antigens by Helicobacter pylori.
Åpne denne publikasjonen i ny fane eller vindu >>Characterization of BabA independent binding activity for ABO blood group antigens by Helicobacter pylori
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(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-56319 (URN)
Tilgjengelig fra: 2012-06-14 Laget: 2012-06-14 Sist oppdatert: 2024-07-02bibliografisk kontrollert
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