The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associated Escherichia coli.
The aetiology of Crohn's disease (CD) involves disorders in host genetic factors and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are receiving increased attention because in studies of mucosa-associated microbiota, they are more prevalent in CD patients than in healthy subjects. AIEC are associated both with ileal and colonic disease phenotypes. In this study, we reported a protease called Vat-AIEC from AIEC that favours the mucosa colonization. The deletion of the Vat-AIEC-encoding gene resulted in an adhesion-impaired phenotype in vitro and affected the colonization of bacteria in contact with intestinal epithelial cells in a murine intestinal loop model, and also their gut colonization in vivo. Furthermore, unlike LF82Δvat-AIEC, wild-type AIEC reference strain LF82 was able to penetrate a mucus column extensively and promoted the degradation of mucins and a decrease in mucus viscosity. Vat-AIEC transcription was stimulated by several chemical conditions found in the ileum environment. Finally, the screening of E. coli strains isolated from CD patients revealed a preferential vat-AIEC association with AIEC strains belonging to the B2 phylogroup. Overall, this study revealed a new component of AIEC virulence that might favour their implantation in the gut of CD patients.
Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.|Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Lucie
L
Gibold
Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Estelle
E
Garenaux
Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Guillaume
G
Dalmasso
Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.
Camille
C
Gallucci
Equipe Biophysique Neurosensorielle, Faculté de Pharmacie, Université d'Auvergne, UMR INSERM 1107, Clermont-Ferrand, France.
David
D
Cia
Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.|Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Benoit
B
Mottet-Auselo
Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.|Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Tiphanie
T
Faïs
Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Arlette
A
Darfeuille-Michaud
Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Hang Thi Thu
HT
Nguyen
Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Nicolas
N
Barnich
Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.|Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Richard
R
Bonnet
Laboratoire de Bactériologie, Centre Hospitalo-Universitaire Clermont-Ferrand, Clermont-Ferrand, France.|Microbes, Intestins, Inflammation et Susceptibilité de l'Hôte, Université d'Auvergne, INSERM U1071, INRA USC2018, Clermont-Ferrand, France.
Julien
J
Delmas
D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000382:microbiology; D051379:Mice; D009093:Mucus / Q000382:microbiology
D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; C000605763:vacuolating autotransporter toxin, E coli
AIEC; Crohn's disease; Escherichia coli; mucinase; mucins; serine protease