Research Article

Laboratory Investigation (2007) 87, 1042–1054. doi:10.1038/labinvest.3700661; published online 30 July 2007

Invasive Escherichia coli are a feature of Crohn's disease

Maiko Sasaki1, Shanti V Sitaraman1, Brian A Babbin2, Peter Gerner-Smidt3, Efrain M Ribot3, Nancy Garrett3, Joel A Alpern4, Adil Akyildiz2, Arianne L Theiss1, Asma Nusrat2 and Jan-Michael A Klapproth1

  1. 1Internal Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA, USA
  2. 2Department of Pathology, Emory University, Atlanta, GA, USA
  3. 3National Center for Zoonotic, Vectorborne and Enteric Diseases, Center for Disease Control and Prevention, Atlanta, GA, USA
  4. 4Department of Medicine, Atlanta, GA, USA

Correspondence: Dr J-MA Klapproth, MD, Internal Medicine, Division of Digestive Diseases, Emory University, 615 Michael Street, Suite 201, Atlanta, GA 30322, USA. E-mail jklappr@emory.edu

Received 8 February 2007; Revised 7 June 2007; Accepted 8 June 2007; Published online 30 July 2007.

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Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory conditions of the gut. Our goal was to investigate if invasive Escherichia coli strains were present in patients with inflammatory bowel disease (IBD). Bacterial strains were isolated from biopsy material obtained from normal controls, and patients with a clinical diagnosis of CD and UC. Invasive bacteria were characterized by gentamicin protection assay and biochemical profiling (Api-20E). Strains were characterized by induction of cytokine expression in epithelial and macrophage cell cultures, measurement of epithelial barrier function, and confocal microscopy. Of all invasive bacterial strains in CD 98.9% were identified as E. coli as opposed to 42.1% in UC and 2.1% in normal controls. Epithelial invasion in vitro was significantly higher for CD-associated E. coli (8.4%, plusminus5.5 of initial inoculum (I/O)) in comparison to UC (2.5%, plusminus0.4 I/O), but highest for strains from inflamed CD tissue (11.3%, plusminus4.3 I/O). Both, CD and UC E. coli strains induced high mean TNF-alpha expression in macrophage cell lines (2604.8 pg/105 cells, plusminus447.4; 2,402.6 pg/105 cells, plusminus476.3, respectively), but concentrations were significantly higher for isolates from inflamed CD tissue (3071.3 pg/105 cells, plusminus226.0). Invasive E. coli from IBD tissue induced similar concentrations of interleukin (IL)-8 in epithelial cell cultures, but strains from inflamed CD tissue induced significantly less epithelial IL-8 (674.1 pg/105 cells, plusminus58.0 vs 920.5 pg/105 cells, plusminus94.6). IBD-associated E. coli strains significantly decreased transepithelial resistance, induced disorganization of F-actin and displacement of ZO-1, and E-cadherin from the apical junctional complex (AJC). In comparison to normal controls and UC, E. coli are more prevalent in CD, are highly invasive, and do not encode for known effector proteins. E. coli strains from IBD patients regulate cytokine expression and epithelial barrier function, two pathological features of IBD.

Keywords:

inflammatory bowel disease, Escherichia coli, invasion, interleukin-8, tumor necrosis factor-alpha, epithelial barrier function

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