The Complement Regulator CD46 Is Bactericidal to Helicobacter pylori and Blocks Urease ActivityShow others and affiliations
2011 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, no 3, p. 918-928Article 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 theurease 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
Baltimore: Williams & Wilkins Co , 2011. Vol. 141, no 3, p. 918-928
Keywords [en]
AhpC, Stomach Cancer, Bacterial Infection, Antibiotic
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:umu:diva-47390DOI: 10.1053/j.gastro.2011.05.009Scopus ID: 2-s2.0-80052134584OAI: oai:DiVA.org:umu-47390DiVA, id: diva2:443576
2011-09-262011-09-202023-03-24Bibliographically approved