Point mutations in FimH adhesin of Crohn's disease-associated adherent-invasive Escherichia coli enhance intestinal inflammatory response

Adherent-invasive Escherichia coli (AIEC) are abnormally predominant on Crohn's disease (CD) ileal mucosa. AIEC reference strain LF82 adheres to ileal enterocytes via the common type 1 pili adhesin FimH and recognizes CEACAM6 receptors abnormally expressed on CD ileal epithelial cells. The fimH...

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Bibliographic Details
Published in:PLoS pathogens 2013-01, Vol.9 (1), p.e1003141-e1003141
Main Authors: Dreux, Nicolas, Denizot, Jérémy, Martinez-Medina, Margarita, Mellmann, Alexander, Billig, Maria, Kisiela, Dagmara, Chattopadhyay, Sujay, Sokurenko, Evgeni, Neut, Christel, Gower-Rousseau, Corinne, Colombel, Jean-Frédéric, Bonnet, Richard, Darfeuille-Michaud, Arlette, Barnich, Nicolas
Format: Article
Language:English
Subjects:
Adhesins, Escherichia coli - genetics
Adhesins, Escherichia coli - metabolism
Animals
Antigens, CD - metabolism
Bacteria
Bacterial Adhesion
Bacteriology
Biochemistry, Molecular Biology
Biology
Cell adhesion & migration
Cell Adhesion Molecules - metabolism
Cell Behavior
Cell Line, Tumor
Cellular Biology
Colitis - metabolism
Colitis - pathology
Crohn Disease - metabolism
Crohn Disease - microbiology
Crohn's disease
E coli
Enterocytes - metabolism
Enterocytes - microbiology
Enterocytes - pathology
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli - pathogenicity
Escherichia coli Infections - metabolism
Escherichia coli Infections - microbiology
Fimbriae Proteins - genetics
Fimbriae Proteins - metabolism
Gene mutations
Genes, Bacterial - genetics
Genetic aspects
Genomics
GPI-Linked Proteins - metabolism
Health aspects
Human health and pathology
Humans
Hépatology and Gastroenterology
Ileum - metabolism
Ileum - microbiology
Ileum - pathology
Immunology
Inflammatory bowel disease
Innate immunity
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Laboratory animals
Life Sciences
Male
Mice
Mice, Transgenic
Microbiology and Parasitology
Molecular biology
Mutation
Pathogenesis
Phylogenetics
Physiological aspects
Point Mutation
Virulence (Microbiology)
Virulence Factors
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Summary:Adherent-invasive Escherichia coli (AIEC) are abnormally predominant on Crohn's disease (CD) ileal mucosa. AIEC reference strain LF82 adheres to ileal enterocytes via the common type 1 pili adhesin FimH and recognizes CEACAM6 receptors abnormally expressed on CD ileal epithelial cells. The fimH genes of 45 AIEC and 47 non-AIEC strains were sequenced. The phylogenetic tree based on fimH DNA sequences indicated that AIEC strains predominantly express FimH with amino acid mutations of a recent evolutionary origin - a typical signature of pathoadaptive changes of bacterial pathogens. Point mutations in FimH, some of a unique AIEC-associated nature, confer AIEC bacteria a significantly higher ability to adhere to CEACAM-expressing T84 intestinal epithelial cells. Moreover, in the LF82 strain, the replacement of fimH(LF82) (expressing FimH with an AIEC-associated mutation) with fimH(K12) (expressing FimH of commensal E. coli K12) decreased the ability of bacteria to persist and to induce severe colitis and gut inflammation in infected CEABAC10 transgenic mice expressing human CEACAM receptors. Our results highlight a mechanism of AIEC virulence evolution that involves selection of amino acid mutations in the common bacterial traits, such as FimH protein, and leads to the development of chronic inflammatory bowel disease (IBD) in a genetically susceptible host. The analysis of fimH SNPs may be a useful method to predict the potential virulence of E. coli isolated from IBD patients for diagnostic or epidemiological studies and to identify new strategies for therapeutic intervention to block the interaction between AIEC and gut mucosa in the early stages of IBD.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003141