Activity of species-specific antibiotics against Crohnʼs disease–associated adherent-invasive Escherichia coli

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
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
500151Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES
500152Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES