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Comparative genomics of Crohn's disease-associated adherent-invasive Escherichia coli

O'Brien, Claire; Bringer, Marie-Agnès; Holt, Kathryn E; Gordon, David M; Dubois, Anaëlle L; Barnich, Nicolas; Darfeuille-Michaud, Arlette; Pavli, Paul

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OBJECTIVE Adherent-invasive Escherichia coli (AIEC) are a leading candidate bacterial trigger for Crohn's disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification. Our aim was to identify a molecular property common to the AIEC phenotype. DESIGN 41 B2 phylogroup E. coli strains were isolated from 36 Australian subjects: 19 patients with IBD and 17 without. Adherence/invasion assays...[Show more]

dc.contributor.authorO'Brien, Claire
dc.contributor.authorBringer, Marie-Agnès
dc.contributor.authorHolt, Kathryn E
dc.contributor.authorGordon, David M
dc.contributor.authorDubois, Anaëlle L
dc.contributor.authorBarnich, Nicolas
dc.contributor.authorDarfeuille-Michaud, Arlette
dc.contributor.authorPavli, Paul
dc.date.accessioned2016-10-11T04:58:24Z
dc.date.available2016-10-11T04:58:24Z
dc.identifier.issn0017-5749
dc.identifier.urihttp://hdl.handle.net/1885/109255
dc.description.abstractOBJECTIVE Adherent-invasive Escherichia coli (AIEC) are a leading candidate bacterial trigger for Crohn's disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification. Our aim was to identify a molecular property common to the AIEC phenotype. DESIGN 41 B2 phylogroup E. coli strains were isolated from 36 Australian subjects: 19 patients with IBD and 17 without. Adherence/invasion assays were conducted using the I-407 epithelial cell line and survival/replication assays using the THP-1 macrophage cell line. Cytokine secretion tumour necrosis factor ((TNF)-α, interleukin (IL) 6, IL-8 and IL-10) was measured using ELISA. The genomes were assembled and annotated, and cluster analysis performed using CD-HIT. The resulting matrices were analysed to identify genes unique/more frequent in AIEC strains compared with non-AIEC strains. Base composition differences and clustered regularly interspaced palindromic repeat (CRISPR) analyses were conducted. RESULTS Of all B2 phylogroup strains assessed, 79% could survive and replicate in macrophages. Among them, 11/41 strains (5 CD, 2 UCs, 5 non-IBD) also adhere to and invade epithelial cells, a phenotype assigning them to the AIEC pathovar. The AIEC strains were phylogenetically heterogeneous. We did not identify a gene (or nucleic acid base composition differences) common to all, or the majority of, AIEC. Cytokine secretion and CRISPRs were not associated with the AIEC phenotype. CONCLUSIONS Comparative genomic analysis of AIEC and non-AIEC strains did not identify a molecular property exclusive to the AIEC phenotype. We recommend a broader approach to the identification of the bacteria-host interactions that are important in the pathogenesis of Crohn's disease.
dc.description.sponsorshipThis research was supported by an Australian Academy of Science France-Australia Science Innovation Collaboration early career fellowship; a Gastroenterological Society of Australia (GESA) Clinical Research grant; and funding from the Ministère de la Recherche et de la Technologie, Inserm (UMR1071), INRA (USC-2018); and Nouveau Chercheur EPST from Conseil Régional Auvergne.
dc.publisherBMJ Publishing Group
dc.rightsThis is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/
dc.sourceGut
dc.subjectcrohn's disease
dc.subjectenteric bacterial microflora
dc.subjectintestinal microbiology
dc.titleComparative genomics of Crohn's disease-associated adherent-invasive Escherichia coli
dc.typeJournal article
dc.date.issued2016-04-20
local.publisher.urlhttp://www.bmj.com/company/
local.type.statusPublished Version
local.contributor.affiliationO'Brien, C. L., Medical School, The Australian National University
local.contributor.affiliationPavli, P., Medical School, The Australian National University
local.identifier.essn1468-3288
local.identifier.doi10.1136/gutjnl-2015-311059
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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