Comparative genomics of Crohn's disease-associated adherent-invasive<i>Escherichia coli</i>

O’Brien, Claire; Bringer, Marie-Agnès; Holt, Kathryn E.; Gordon, David M.; Dubois, A.; Barnich, Nicolas; Darfeuille‐Michaud, Arlette; Pavli, Paul

doi:10.1136/gutjnl-2015-311059

Cited by 93 publications

(112 citation statements)

References 60 publications

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“…The clonal analyses of AIEC strains obtained from CD patients through PFGE showed a high degree of genetic variability, which is in agreement with the high variability of the distribution of virulence factors, and is similar to previous publications (Martinez-Medina et al, 2009; De la Fuente et al, 2014; O'Brien et al, 2016). The B2 and D genomic groups were highly prevalent among strains from CD subjects, as has been shown in previous reports (Kotlowski et al, 2007; Martinez-Medina et al, 2009; De la Fuente et al, 2014).…”

Section: Discussionsupporting

confidence: 92%

“…The ability to adhere and invade epithelial cells, and survive intracellularly in macrophages characterizes this group of strains (Darfeuille-Michaud et al, 1998; Boudeau et al, 1999; Glasser et al, 2001; De la Fuente et al, 2014). Several virulence factors have been associated with these pathogenic properties in this pathotype (Conte et al, 2014; O'Brien et al, 2016) however they are not exclusive to AIEC strains (Martinez-Medina and Garcia-Gil, 2014). Interestingly, production of type 1 fimbriae appears to correlate with adhesiveness of AIEC strains and certain FimH variants confer them a higher adhesion to intestinal epithelial cells (Dreux et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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Genetic Diversity and Virulence Determinants of Escherichia coli Strains Isolated from Patients with Crohn's Disease in Spain and Chile

et al. 2017

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Adherent-invasive Escherichia coli (AIEC) strains are genetically variable and virulence factors for AIEC are non-specific. FimH is the most studied pathogenicity-related protein, and there have been few studies on other proteins, such as Serine Protease Autotransporters of Enterobacteriacea (SPATEs). The goal of this study is to characterize E. coli strains isolated from patients with Crohn's disease (CD) in Chile and Spain, and identify genetic differences between strains associated with virulence markers and clonality. We characterized virulence factors and genetic variability by pulse field electrophoresis (PFGE) in 50 E. coli strains isolated from Chilean and Spanish patients with CD, and also determined which of these strains presented an AIEC phenotype. Twenty-six E. coli strains from control patients were also included. PFGE patterns were heterogeneous and we also observed a highly diverse profile of virulence genes among all E. coli strains obtained from patients with CD, including those strains defined as AIEC. Two iron transporter genes chuA, and irp2, were detected in various combinations in 68–84% of CD strains. We found that the most significant individual E. coli genetic marker associated with CD E. coli strains was chuA. In addition, patho-adaptative fimH mutations were absent in some of the highly adherent and invasive strains. The fimH adhesin, the iron transporter irp2, and Class-2 SPATEs did not show a significant association with CD strains. The V27A fimH mutation was detected in the most CD strains. This study highlights the genetic variability of E. coli CD strains from two distinct geographic origins, most of them affiliated with the B2 or D E. coli phylogroups and also reveals that nearly 40% of Chilean and Spanish CD patients are colonized with E.coli with a characteristic AIEC phenotype.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Genetic Diversity and Virulence Determinants of Escherichia coli Strains Isolated from Patients with Crohn's Disease in Spain and Chile

et al. 2017

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“…These pathways provide opportunities for novel therapeutic approaches to block attachment or promote clearance 108, 116 . Unfortunately, current molecular signatures cannot distinguish AIEC from non-pathogenic E coli strains, although sequencing of broad panels of clinical isolates have identified enriched pathways, such as propanediol utilization and iron acquisition 117, 118 . These observations, along with identifying AIEC genes most highly expressed under inflammatory conditions 44 may help to identify specific inhibitors of AIEC pathogenicity.…”

Section: Microbiota In Development and Progression Of Ibdmentioning

confidence: 99%

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

2017

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Intestinal microbiota are involved in the pathogenesis of Crohn’s disease, ulcerative colitis, and pouchitis. We review the mechanisms by which these gut bacteria, fungi, and viruses mediate mucosal homeostasis, via their composite genes (metagenome) and metabolic products (metabolome). We explain how alterations to their profiles and functions under conditions of dysbiosis contribute to inflammation and effector immune responses that mediate inflammatory bowel diseases (IBD) in humans and enterocolitis in mice. It could be possible to engineer the intestinal environment by modifying the microbiota community structure or function to treat patients with IBD— either with individual agents, via dietary management, or as adjuncts to immunosuppressive drugs. We summarize the latest information on therapeutic use of fecal microbial transplantation and propose improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment.

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“…It has been remarkably difficult to identify a specific genetic or molecular marker of AIEC, thus in vitro assays are used to validate AIEC 14 . However, there may be some genetic signatures that differ between the B2 AIEC phylotype compared with other AIEC phylotypes 12 .…”

Section: Aiecmentioning

confidence: 99%

Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli

Shawki

McCole

2017

Cellular and Molecular Gastroenterology and Hepatology

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Pathobiont expansion, such as that of adherent-invasive Escherichia coli (AIEC), is an emerging factor associated with inflammatory bowel disease. The intestinal epithelial barrier is the first line of defense against these pathogens. Inflammation plays a critical role in altering the epithelial barrier and is a major factor involved in promoting the expansion and pathogenesis of AIEC. AIEC in turn can exacerbate intestinal epithelial barrier dysfunction by targeting multiple elements of the barrier. One critical element of the epithelial barrier is the tight junction. Increasing evidence suggests that AIEC may selectively target protein components of tight junctions, leading to increased barrier permeability. This may represent one mechanism by which AIEC could contribute to the development of inflammatory bowel disease. This review article discusses potential mechanisms by which AIEC can disrupt epithelial tight junction function and intestinal barrier function.

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Comparative genomics of Crohn's disease-associated adherent-invasiveEscherichia coli

Cited by 93 publications

References 60 publications

Genetic Diversity and Virulence Determinants of Escherichia coli Strains Isolated from Patients with Crohn's Disease in Spain and Chile

Genetic Diversity and Virulence Determinants of Escherichia coli Strains Isolated from Patients with Crohn's Disease in Spain and Chile

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli

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