Article Text

PDF

Original article
Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer
  1. Maelle Prorok-Hamon1,
  2. Melissa K Friswell1,
  3. Abdullah Alswied1,
  4. Carol L Roberts1,
  5. Fei Song1,
  6. Paul K Flanagan1,
  7. Paul Knight1,
  8. Caroline Codling2,
  9. Julian R Marchesi2,3,
  10. Craig Winstanley4,
  11. Neil Hall5,
  12. Jonathan M Rhodes1,
  13. Barry J Campbell1
  1. 1Department of Gastroenterology, Institute of Translational Medicine, Liverpool, UK
  2. 2Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
  3. 3School of Biosciences, Cardiff University, Cardiff, UK
  4. 4Departments of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, Liverpool, UK
  5. 5Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, UK
  1. Correspondence to Dr Barry Campbell, Department of Gastroenterology, University of Liverpool, Liverpool L69 3GE, UK; bjcampbl{at}liv.ac.uk

Abstract

Objective Colonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates.

Design A fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome).

Results 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin.

Conclusions IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.

  • BACTERIAL ADHERENCE
  • BACTERIAL INTERACTIONS
  • BACTERIAL PATHOGENESIS
  • GUT INFLAMMATION
  • E. COLI

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) 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/3.0/

View Full Text

Statistics from Altmetric.com

Supplementary materials

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.