Journal
GASTROENTEROLOGY
Volume 141, Issue 3, Pages 918-928Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2011.05.009
Keywords
AhpC; Stomach Cancer; Bacterial Infection; Antibiotic
Categories
Funding
- Swedish Research Council
- Swedish Cancer Society
- Knut and Alice Wallenbergs Stiftelse
- Torsten and Ragnar Soderbergs Stiftelse
- Swedish Society for Medicine
- Magnus Bergwalls Stiftelse
- Olga Jonssons Stiftelse
- Stiftelsen Lars Hiertas Minne
- Harald Janssons Stiftelse
- Petrus and Agusta Hedlunds Stiftelse
- Stiftelsen Anna Brita and Bo Castegrens Minne
- Tore Nilssons Stiftelse for Medicinsk Forskning
- Ake Wiberg Stiftelse
- Emil and Ragna Borjessons Stiftelse
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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.
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