Brown, C. L., Smith, K., Wall, D. and Walker, D. (2015) Activity of species-specific antibiotics against Crohnʼs disease–associated adherent-invasive Escherichia coli. Inflammatory Bowel Diseases, 21(10), pp. 2372-2382. (doi: 10.1097/MIB.0000000000000488) (PMID:26177305)
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Abstract
Background: Crohn's disease (CD) is associated with bacterial dysbiosis that frequently includes colonization by adherent-invasive Escherichia coli (AIEC). AIEC are adept at forming biofilms and are able to invade host cells and stimulate the production of proinflammatory cytokines. The use of traditional antibiotics for the treatment of CD shows limited efficacy. In this study, we investigate the use of species-specific antibiotics termed colicins for treatment of CD-associated AIEC. Methods: Colicin activity was tested against a range of AIEC isolates growing in the planktonic and biofilm mode of growth. Colicins were also tested against AIEC bacteria associated with T84 intestinal epithelial cells and surviving inside RAW264.7 macrophages using adhesion assays and gentamicin protection assay, respectively. Uptake of colicins into eukaryotic cells was visualized using confocal microscopy. The effect of colicin treatment on the production of proinflammatory cytokine tumor necrosis factor alpha by macrophages was assessed by an enzyme-linked immunosorbent assay. Results: Colicins show potent activity against AIEC bacteria growing as biofilms when delivered either as a purified protein or through a colicin-producing bacterial strain. In addition, colicins E1 and E9 are able to kill cell-associated and intracellular AIEC, but do not show toxicity toward macrophage cells or stimulate the production of proinflammatory cytokines. Colicin killing of intracellular bacteria occurs after entry of colicin protein into AIEC-infected macrophage compartments by actin-mediated endocytosis. Conclusions: Our results demonstrate the potential of colicins as highly selective probiotic therapeutics for the eradication of E. coli from the gastrointestinal tract of patients with CD.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Walker, Professor Daniel and Smith, Ms Karen and Wall, Dr Daniel |
Authors: | Brown, C. L., Smith, K., Wall, D., and Walker, D. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Inflammatory Bowel Diseases |
Publisher: | Lippincott Williams & Wilkins |
ISSN: | 1078-0998 |
ISSN (Online): | 1536-4844 |
Copyright Holders: | Copyright © 2015 Copyright © 2015 Crohn’s and Colitis Foundation of America, Inc. |
First Published: | First published in Inflammatory Bowel Diseases |
Publisher Policy: | Reproduced under a Creative Commons License |
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