The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
2011 (English)In: Gastroenterology, ISSN 0016-5085, Vol. 141, no 3, 918-928 p.Article in journal (Refereed) Published
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.
AhpC, Stomach Cancer, Bacterial Infection
Microbiology Gastroenterology and Hepatology
Research subject Microbiology
IdentifiersURN: urn:nbn:se:su:diva-63669DOI: 10.1053/j.gastro.2011.05.009ISI: 000294281200032PubMedID: 21699774OAI: oai:DiVA.org:su-63669DiVA: diva2:451664
FunderSwedish Research CouncilKnut and Alice Wallenberg Foundation