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Helicobacter pylori sabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
The Swedish Institute for Infectious Disease Control, Solna, Sweden and Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
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2006 (English)In: Medical Microbiology and Immmunology, ISSN 0300-8584, E-ISSN 1432-1831, Vol. 195, no 4, 195-206 p.Article in journal (Refereed) Published
Abstract [en]

The human pathogen Helicobacter pylori expresses two dominant adhesins; the Lewis b blood group antigen binding adhesin, BabA, and the sialic acid-binding adhesin, SabA. These adhesins recognize specific carbohydrate moieties of the gastric epithelium, i.e. the Lewis b antigen, Leb, and the sialyl-Lewis x antigen, sLex, respectively, which promote infection and inflammatory processes in the gastroduodenal tract. To assess the contribution of each of BabA, SabA and the neutrophil activating protein (HP-NAP) in a local inflammation, we investigated the traits of H. pylori mutants in their capacity to interact with and stimulate human neutrophils. We thence found that the SabA adhesin was not only the key inducer of oxidative metabolism (Unemo et al. J Biol Chem 280:15390–15397, 2005), but also essential in phagocytosis induction, as evaluated by flow cytometry, fluorescence microscopy and luminol-enhanced chemiluminescence. The napA deletion resulted in enhanced generation of reactive oxygen species and impaired adherence to the host cells. In conclusion, the SabA adhesin stimulates human neutrophils through selectin-mimicry. Interestingly, HP-NAP modulates the oxidative burst, which could tune the impact of the H. pylori infection for establishment of balanced and chronic inflammation of the gastric mucosa.

Place, publisher, year, edition, pages
2006. Vol. 195, no 4, 195-206 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-38156DOI: 10.1007/s00430-006-0018-xLocal ID: 42125OAI: oai:DiVA.org:liu-38156DiVA: diva2:259005
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Characterisation of surface traits of Helicobacter pylori and their role in the infectious process
Open this publication in new window or tab >>Characterisation of surface traits of Helicobacter pylori and their role in the infectious process
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The surface appendages of bacteria determine the initial contact with host cells. Characterisation of functional organisation and spatial distribution of adhesive traits of outer membrane components of Gram-negative bacteria is a key issue in studies of the parasite-host cell interaction.

With focus on the enteropathogenic Helicobacter pylori, evidenced to cause chronic gastric infections in humans, detergent-digested freeze fracture replica labelling was applied for ultrastructural analyses of envelope distribution of the virulence factors blood group antigen binding adhesin (BabA), and the carbonic anhydrases (α-CA, ß-CA). In a preliminary study the methodology was also used to study the bacteria-host contact between phagocytosing human neutrophils and wild-type H. pylori.

In parallel, bacterial traits were analysed from a molecular and biochemical perspective. This included the specific roles of the BabA and the sialic acid-binding adhesin (SabA), and the neutrophil activating protein (HP-NAP) in neutrophilic stimulation and subsequent inflammatory process. It was concluded that SabA is crucial in the initiation of a neutrophilic response in the mediated inflammation.

This thesis has demonstrated the synergistic application of ultrastructural, molecular and cellular microbiology tools for delineating complex patterns in bacteria-host interactions, thus utilising the well-characterised and clinically important human pathogen H. pylori. This approach could be applicable to other Gram-negative species to clarify known and discern new virulence mechanisms in the multifaceted field of bacterial pathogenesis and bacterial interactions with human host cells.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 77 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 805
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26665 (URN)11231 (Local ID)91-7373-490-X (ISBN)11231 (Archive number)11231 (OAI)
Public defence
2003-10-03, Elsa Brändströmsalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-15Bibliographically approved

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Petersson, ChristofferForsberg, MariaForslund, TonyMagnusson, Karl-Eric

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