Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans

• Published in: PloS one 2009-05, Vol.4 (5), p.e5517-e5517
• Main Authors: Maddocks, Oliver D K, Short, Abigail J, Donnenberg, Michael S, Bader, Scott, Harrison, David J
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - microbiology; Analysis; Apoptosis; Bacteria; Bacterial Adhesion - genetics; Bacterial infections; Biopsy; Cancer; Cell Line, Tumor; Chronic infection; Citrobacter; Coliforms; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - microbiology; Crypts; Cytochrome; Cytochrome c; Deoxyribonucleic acid; Diarrhea; DNA; DNA methylation; DNA repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Down-Regulation; E coli; Effector cells; Enteropathogenic Escherichia coli - pathogenicity; Epithelial cells; Escherichia coli; Escherichia coli - pathogenicity; Escherichia coli - physiology; Fluorescent Antibody Technique; Gastroenterology and Hepatology/Gastrointestinal Cancers; Gastroenterology and Hepatology/Gastrointestinal Infections; Gene expression; Genes; Genetic aspects; Genetics; Health aspects; Helicobacter pylori; Humans; Immunofluorescence; Industrialized nations; Infection; Infections; Infectious diseases; Intestinal Mucosa - microbiology; Intestine; Intimin; Kinases; Medicine; Mismatch repair; MLH1 protein; Molecular Biology/DNA Repair; MSH2 protein; Mucosa; Mutation; Pathology; Patients; Phosphorylation; Proteins; Proteomes; Repair; Studies; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005517

Mucosa-associated Escherichia coli are frequently found in the colonic mucosa of patients with colorectal adenocarcinoma, but rarely in healthy controls. Chronic mucosal E. coli infection has therefore been linked to colonic tumourigenesis. E. coli strains carrying eae (encoding the bacterial adhesion protein intimin) attach intimately to the intestinal mucosa and are classed as attaching and effacing E. coli (AEEC). Enteropathogenic Escherichia coli (EPEC) are the most common form of AEEC identified in man. EPEC utilise a type III secretion system to translocate effector proteins into host cells and infection induces wide-ranging effects on the host cell proteome. We hypothesised that EPEC infection could influence molecular pathways involved in colorectal tumourigenesis. When co-cultured with human colorectal cell lines, EPEC dramatically downregulated the expression of key DNA mismatch repair proteins MSH2 and MLH1 in an attachment specific manner. Cytochrome c staining and TUNEL analysis confirmed that this effect was not a consequence of apoptosis/necrosis. Ex vivo human colonic mucosa was co-cultured with EPEC and probed by immunofluorescence to locate adherent bacteria. EPEC entered 10% of colonic crypts and adhered to crypt epithelial cells, often in the proliferative compartment. Adenocarcinoma and normal colonic mucosa from colorectal cancer patients (n = 20) was probed by immunofluorescence and PCR for AEEC. Mucosa-associated E. coli were found on 10/20 (50%) adenocarcinomas and 3/20 (15%) normal mucosa samples (P