Role of Decreased Levels of Fis Histone-Like Protein in Crohn's Disease-Associated Adherent Invasive E scherichia coli LF82 Bacteria Interacting with Intestinal Epithelial Cells

Author:

Miquel Sylvie12,Claret Laurent123,Bonnet Richard124,Dorboz Imen5,Barnich Nicolas123,Darfeuille-Michaud Arlette123

Affiliation:

1. Clermont Université, Université d'Auvergne, JE 2526, F-63000 Clermont-Ferrand, France

2. INRA, USC-2018, Clermont-Ferrand, France

3. Institut Universitaire de Technologie, Université d'Auvergne, F-63172 Aubière, France

4. Centre Hospitalier Universitaire, Bactériologie, F-63003 Clermont-Ferrand, France

5. Clermont Université, Université d'Auvergne, GreD, UMR6247/UMR911 CNRS/Inserm, F-63000 Clermont-Ferrand, France

Abstract

ABSTRACT The interaction of Crohn's disease (CD)-associated adherent-invasive Escherichia coli (AIEC) strain LF82 with intestinal epithelial cells depends on surface appendages, such as type 1 pili and flagella. Histone-like proteins operate as global regulators to control the expression of these virulence factors. We evaluated the role of histone-like proteins in AIEC reference strain LF82 during infection of intestinal epithelial cells, Intestine-407, and observed that the fis mRNA level was decreased. The role of Fis in AIEC LF82 was determined by studying the phenotype of an LF82 fis ::Km mutant. This was the first mutant of strain LF82 that has been described thus far that is unable to express flagellin but still able to produce type 1 pili. The cyclic-di-GMP pathway linking flagella and type 1 pilus expression is not involved in Fis-mediated regulation, and we identified in the present study Fis-binding sites located upstream of the fimE gene and in the intergenic region between fimB and nanC of the fim operon encoding type 1 pili. The major consequence of decreased Fis expression in AIEC bacteria in contact with host cells is a direct downregulation of fimE expression, leading to the preferential ON phase of the fimS element. Thus, by maintaining type 1 pilus expression, AIEC bacteria, which interact with the gut mucosa, have greater ability to colonize and to induce inflammation in CD patients.

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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