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The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0002-7115-9751
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2011 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, no 3, 918-928 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.

METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.

RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.

CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.

Place, publisher, year, edition, pages
2011. Vol. 141, no 3, 918-928 p.
Keyword [en]
AhpC, Stomach Cancer, Bacterial Infection
National Category
Microbiology Gastroenterology and Hepatology
Research subject
Microbiology
Identifiers
URN: urn:nbn:se:su:diva-63669DOI: 10.1053/j.gastro.2011.05.009ISI: 000294281200032PubMedID: 21699774OAI: oai:DiVA.org:su-63669DiVA: diva2:451664
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2011-10-26 Created: 2011-10-26 Last updated: 2017-12-08Bibliographically approved

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Basmarke-Wehelie, RahmaSjölinder, HongElofsson, ArneAro, HelenaJonsson, Ann-Beth
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