Role of decreased levels of Fis histone-like protein in Crohn's disease-associated adherent invasive Escherichia coli LF82 bacteria interacting with intestinal epithelial cells.
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.
Miquel
Sylvie
S
Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Claret
Laurent
L
Bonnet
Richard
R
Dorboz
Imen
I
Barnich
Nicolas
N
Darfeuille-Michaud
Arlette
A
D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001665:Binding Sites; D003424:Crohn Disease / Q000382:microbiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D004847:Epithelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000235:genetics; D035021:Factor For Inversion Stimulation Protein / Q000096:biosynthesis* / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000502:physiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D019426:Integrases / Q000235:genetics; D016254:Mutagenesis, Insertional; D018272:Porins / Q000235:genetics; D011401:Promoter Regions, Genetic
D001425:Bacterial Outer Membrane Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D035021:Factor For Inversion Stimulation Protein; C501034:Fis protein, E coli; C528455:NanC protein, E coli; D018272:Porins; C081956:fimB protein, E coli; C081955:fimE protein, E coli; D019426:Integrases