Targeting HuR-Vav3 mRNA interaction prevents Pseudomonas aeruginosa adhesion to the cystic fibrosis airway epithelium. - Université de Lille Accéder directement au contenu
Article Dans Une Revue JCI Insight Année : 2023

Targeting HuR-Vav3 mRNA interaction prevents Pseudomonas aeruginosa adhesion to the cystic fibrosis airway epithelium.

Mehdi Badaoui
Alexandre Luscher
  • Fonction : Auteur
Marc Bacchetta
  • Fonction : Auteur
Thilo Köhler
  • Fonction : Auteur
Michelango Foti
  • Fonction : Auteur
Marc Chanson
  • Fonction : Auteur

Résumé

Cystic fibrosis (CF) is characterized by chronic bacterial infections leading to progressive bronchiectasis and respiratory failure. Pseudomonas aeruginosa (Pa) is the predominant opportunistic pathogen infecting the CF airways. The guanine nucleotide exchange factor Vav3 plays a critical role in Pa adhesion to the CF airways by inducing luminal fibronectin deposition that favors bacteria trapping. Here we report that Vav3 overexpression in CF is caused by upregulation of the mRNA-stabilizing protein HuR. We found that HuR accumulates in the cytoplasm of CF airway epithelial cells and that it binds to and stabilizes Vav3 mRNA. Interestingly, disruption of the HuR-Vav3 mRNA interaction improved the CF epithelial integrity, inhibited the formation of the fibronectin-made bacterial docking platforms, and prevented Pa adhesion to the CF airway epithelium. These findings indicate that targeting HuR represents a promising antiadhesive approach in CF that can prevent initial stages of Pa infection in a context of emergence of multidrug-resistant pathogens.
Fichier principal
Vignette du fichier
161961.2-20230130120612-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf (6.44 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04419076 , version 1 (26-01-2024)

Licence

Identifiants

Citer

Mehdi Badaoui, Cyril Sobolewski, Alexandre Luscher, Marc Bacchetta, Thilo Köhler, et al.. Targeting HuR-Vav3 mRNA interaction prevents Pseudomonas aeruginosa adhesion to the cystic fibrosis airway epithelium.. JCI Insight, 2023, JCI Insight, 8 (3), pp.e161961. ⟨10.1172/jci.insight.161961⟩. ⟨hal-04419076⟩

Collections

UNIV-LILLE
7 Consultations
3 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More